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CANCER-CAUSING CHEMICALS-PART 1
Safety of Cosmetics and Hair Dyes
HEARINGS
BEFORE THE
SUBCOMMITTEE ON
OVERSIGHT AND INVESTIGATIONS
OF THE
COMMITTEE ON
INTERSTATE AND FOREIGN COMMERCE
HOUSE OF REPRESENTATIVES
NINETY-FIFTH CONGRESS
SECOND SESSION
ON
TI~E REVIEW OF THE ADEQUACY OF EXISTING LAWS DE-
SIGNED TO PROTECT THE PUBLIC FROM EXPOSURE TO CAN-
CER CAUSING AND OTHER TOXIC CHEMICALS IN HAIR DYES
AND COSMETIC PRODUCTS
JANUARY 23 AND 26; FEBRUARY 2 AND 3, 1978
Serial No. 95-91
Printed for the use of the
Committee on Interstate and Foreign Commerce
U.S. GOVERNMENT PRINTING OFFICE
24-6000 WASHINGTON: 1978
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COMMITTEB ON INTERSTATE AND ~`OREIGN COMMERCE
HARLEY 0. STAGGERS, West Virginia, Cha4rman
JOHj~i B. MOSS, California
JOHN I~. DINGELL, Michigan
PAULO. ROGERS, Florida
LIONEL VAN DEERLIN, California
FRED B. ROONEY, Pennsylvania
JOHN M. MURPHY, New York
DAVXD B. SATTERFIELD II, Virginia
BOB ECKHARDT, Texas.
RIChARDSON PREYER, North Carolina
CHARLES J. CARNEY, Ohio
RALPH H. METCALFE, Illinois
JAMES H. SCHEUER, New York
RICHARD L. OTTINGER, New York
HENRY A. WAXMAN, California
ROBERT (BOB) KRUEGER, Texas
TIMOTHY E. WIETH, Colorado
PHILIP R. SHARP, Indiana
JAMES J. FLORIO, New Jersey
ANTHONY TOBY MOFFETT, Connecticut
JIM SANTINI, Nevada
ANDREW MAGUIRE, New Jersey
MART~ A. RUSSO, Illinois
BDWARD J. MARKEY, Massachusetts
THOMAS A. LUKEN, Ohio
DOUG WALOREN, Pennsylvania
BOB GAMMAGE, Texas
ALBERT GORE, JR., Tennessee
BARBA~ItA A. MIKULSKI, Maryland
W. B. WILLIAMSON, Chief Clerk and Staff Director
KENNETH J. PAINTER, First Assistant Clerk
ELEANOR A. DINKIN5, Assistant Clerk
WILLIAM L. BURNS, Printing Editor
JIM SANTINI, Nevada
THOMAS A. LUKEN, Ohio
DOUG WALGREN, Pennsylvania
ALBERT GORE, JR., Tennessee
CHARLES J. cARNEY, Ohio
HENRY 4~ WAXMAN, California
PHILIP B. SHARP, Indiana
ANTHONY TOBY MOFFETT, Connecticut
ANDREWMAGUIRE, New Jersey
ROBERT (BOB) KRUEGER, Texas
HARLEY 0. STAGGERS, West Virginia
(ExOfficio)
ELLIOT A. SEGAL, Health Task Force Director
LESTER 0. BRoWN, Special Assistant
SUSAN LEAL, Counsel
KATHERINE C. MEYERS, Special Assistant
ALLEGRA MCMANLTS, Staff Assistant
LOwELL DODGE, Oversight Ta8k Force Director
JOHN GALLOWAY, Energy Task Force Director
JOHN MCELROY ATKISSON, Counsel to the SubcommQtee
JAMES L. NELLIGAN, Operations Director
J. THOMAS GREENE, Coun8el to the Chairman
BERNARD J. WUNDER, Jr., Minority Counsel
SAMUEL L. DEVINE, Ohio*
JAMES T. BROYHILL, North Carolina
TIM LEE CARTER, Kentucky
CLARENCE J. BROWN, Ohio
JOE SKUBITZ, Kansas
JAMRS M. COLLINS, Texas
LOUIS FREY, JR., Florida
NORMAN F. LENT, New York
1iDWARD R. MADIGAN, Illinois
CARLiOS J. MOOREIIEAD, Caiifornia
MATTHEW J. RINALDO, New Jersey
W. HENSON MOORE, Louisiana
DAVE STOCKMAN, Michigan
MARC L. MARKS, Pennsylvania
SUBOOMMITTHE ON OVHRSIGHT AND INVESTIGATIONS
JOHN B. MOSS, California, Chairman
JAMES M. COLLINS, Texas
NORMAN F. LENT, New York
MATTHEW J. RINALDO, New Jersey
DAVE STOCKMAN, Michigan
MARC L. MARKS, Pennsylvania
SAMUEL L. J)EVINE, Ohio (Ex Officio)
(II)
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CONTENTS
Hearings held on- Page
January 23, 1978 1
January 26, 1978 89
February 2, 1978 213
February 3, 1978
Testimony of-
Ahart, Gregory J., Director, Human Resources Division, General
Accounting Office 351
Baier, Edward J., Deputy Director, National Institute for Occupa-
tional Safety and Health, Center for Disease Control, Department
of Health, Education, and Welfare 50
Cooper, Richard, Chief Counsel, Food and Drug Administration,
Public Health Service, Department of Health, Education, and
Welfare 368
Corbett, John F., Ph. D. chairman, Hair Dye Technical Committee,
Cosmetic, Toiletry & F~ragrance Association Inc 90, 214, 314
Dach, Leslie, science associate, Environmental Defense Fund 214
Estrin, Norman F., Ph. D., vice president, science, Cosmetic, Toiletry
& Fragrance Association, Inc 90
Fine, David H., Ph. D., senior scientist, Thermo Electron Corp 334
Fraumeni, Joseph, Jr. M.D., Chief, Environmental Epidemiology
Branch, Division of Oancer Cause and Prevention, National Cancer
Institute, National Institutes of Health, Department of Health, Edu-
cation, and Welfare 4
Griesemer, Richard A. D.V.M., Ph D., Associate Director for Car-
cinogenesis Testing i'rogram, Division of Cancer Cause and Pre-
vention, National Cancer Institiite, National Institutes of Health,
Departmer~t of Health, Education, and Welfare 4
Highland, Joseph, Ph. D., director, Toxic Chemicals Program, Envi-
ronmental Defense Fund 214
Hutt, Peter Barton, counsel, Cosmetic, Toiletry & Fragrance Asso-
ciation, Inc 90
Johnson, Anita, staff attorney, Environmental Defense Fund 214
Jojokian, Albert B., Assistant Director, Human Resources Division,
General Accounting Office 351
Kennedy, Hon. Donald, Ph. D., Commissioner, Food and Drug
Administration, Public Health Service, Department of Health,
Education, and Welfare 368
Linz, James, Supervisory Auditor, Human Resources Division, Gen-
eral Accounting Office 351
Merritt, James H., president, Cosm,etic Toiletry & Fragrance Asso-
ciation, Inc 90
Page, Norbert P., D.V.M., Chief, Priorities and Research Analysis
Branch, Division of Criteria Documentation ~nd Standards Devel-
opment, National Institute for Occupational Safety and Health
Center for Disease Control, Department of Health, Education anci
Welfare 50
Roberts, Howard R., Ph. D., Director Bureau of Foods, Food and
Drug Administration, Public Health ~ervice, Department of Health,
Education and Welfare 368
Scheuplein, ~Robert J., Ph. D., Chief, Dermal and Ocular Toxicity
Branch, Division of Toxicity, Bureau of Foods, Food and Drug
Administration, Public Health Service, Department of Health,
Education, and Welfare_ - 368
Upton, Arthur C., M.D., Director, National Cancer Institute, Na-
tional Institutes of Health, Department of Health, Education, and
Welfare
Walrath, Judy, Ph. D., school of medicine, Yale University 346
(III)
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Iv
Additional material submitted for the record by:
Cosmetic, Toiletry & Fragrance Association, Inc.:
"Cosmetic Ingredient Review Procedures," revised (includes
amendments approved by CIR steering committee and CTFA
board of directors as of. December 20, 1976) 97
Draft report to the legislative planning group of CTFA, dated
February 8, 1974, Arthur D. Little, Inc 145
List of companies, product tested, and results re nitrosamines 187
General Accounting Office:
List of products containing ingredients with toxic effects listed
in the 1977 CTFA cosmetic. ingredient dictionary as reported
in the 1976 NIOSH Registry of Toxic Effects of Chemical
Substances 361
Uses reported to FDA by cosmetic manufacturers of cosmetic
ingredients banned by the European Economic Community
directive 365
Health, Education, and Welfare Department:
Award fee arrangement-Tracor Jitco 48
Costs to exploit existing capability * 29
Occupational carcinogens, NIOSH recommendations - . 53
Table indicating chemical tested, date animal was killed, date
pathology completed, date pathology confirmed, and date of
draft report 16
Oversight and Investigations Subcommittee, Committee on Inter-
state and Foreign Commerce:
Abstract-cancer incidence amongst cosmetologists 190
Correspondence dated May 21 and June 21, 1977- between
Chairman Moss and National Institutes of Health re hair
dyes and hairdye constituents 24
Excerpt from: Some Negative Findings (Polio, Smallpox,
Tetitnus and Diptheria-Vaccines; Beauticians) and Evalua-.
tion of Risks 197
Graph of final reports compared to projected reports by the
National Cancer Institute 9
Letter dated January 5, 1978, with attachment from Dr. Grie-
semer, National Cancer Institute, to Chairman Moss re
preliminary data on NCI's bioassays of hair dyes and related
chemicals 3
Letter dated January 11, 1978, with attachment~ from Robert
W. Morgan, M.D., professor, University of Toronto, to
Chairman Moss re results of study concerning the relation-
ship of hair dyes to bladder cancer 209
Letter dated January 17, 1978, from J. Wister Meigs, M.D.,
director, clinical professor, epidemiology, Connecticut Cancer
Epidemiology Program, to Chairman Moss re opinion that
cosmetologists in Connecticut had not experienced an excess
overrisk of cancer 192
Letter dated January 20, 1978, from Alvan R. Feinstein, M.D.,
professor of medicine and epidemiology7 Yale University
8chool of Medicine, to Mr. Com~er Fay, vice president, Clairol
re comments on "Restropective Survey of Cancer in Rela-
~ion to Occupation, by Decoufie, et al, and a manuscript draft,
preliminary report entitled, "Occupational Characteristics
of Disabled Pemale Workers," by J. Kennedy and R. Spirtas 62
Letter dated January 30, 1978, from Alvan R. Feinstein, M.D.,
professor of Medicine and Epidemiology, Yale University, to
Chairman Moss re critical review of studies of hairdressers.
and cosmetologists performed by Dr. E. Cuyler Hammond and
by Dr. J. Wister Meigs 344
Letter dated February 24, 1978, with attachments, from J. Donald
Millar, M.D., Assistant Surgeon General, Acting Director,
NIOSH, to Chairman Moss re comments from Dr. Irving
I~essler and Dr. Alvan Feinstein on two NIOSH studies
indicating that cosmetologists and hairdressers may be at
increased risk of cancer -- * 78
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V
Additional material submitted for the record by-Continued
Oversight and Investigations Subcommittee-Continued
Meftiorandum dated January 21 1978, from Irving I. I~essler,
M.D., Dr. P. IL, professor 0! epidemiology, Johns Hopkins
University, to Dr. John Menkart, Clairol, Inc., re evaluation
of the NIOSH Rosweil Park Memorial Institute study oited in
the January 13, NIOSH Current Intelligence Bulletin 66
Toxic effects of ingredients listed in the 1977 CTFA cosmetic
ingredient dictionary as reported in the 1976 NIOSH Registry
of Toxic Effects of Chemical Substances 358
Thormo Electron Corp., table 5-some examples of known and
suspected human exposure to N-nitroso compounds 338
Appendix A:
Chart 1-List of chemicals in bioassay program that are hair dye
ingredients
Chart 2-Selected examples of chemicals listed in the bioassay
program 396
Appendix 13:
Affidavit of Dr. Bruce N. Ames conceruing hair dye chemicals 397
Hair Dye Components: Review of Mutagenicity and Other Short-
Term Tests, Cheryl Gold and Bruce N. Ames, Department of
Biochemistry, University of California 399
Hair Dyes Are Muta~genic: Identification of a Variety of Mttta-
genic Ingredients, Bruce N. Ames, H. 0. Kammen, and Edith
Yamasaki - 427
Interview with Dr. Bruce Ames, a biochemist and geneticist, Univer-
sity of California at Berkeley, on Thursday, January 12, 1978,
with Lester Brown of the Subcommittee staff 432
Appendix C-Letter dated February 3, 1978, from Stephen M. $rown,
M.D., M.P.H. Head, Epidemiology Program National Institute of
Environment ~Iealth Sciences, to Chairman 1~'Ioss re studies linking
cancer with human exposure to hair dyes 452
Appendix D-Letter dated February 14, 1978, from Grover C. Wrenn,
Director, Health Standards Programs, Department of Labor, to Chair
man Moss with statement attached 455
ORGANIZATIONS REPRESENTED AT H1~ARINGS
Cosmetic, Toiletry & Fragrance Association, Inc.:
Corbett John F. Pb. D., chairman, Hair Dye Technical Committee.
Estrin, I~orman 1?., Ph. D., vice president, science.
Hutt, Peter Barton, counsel.
Merritt, James H., president.
Environmental DefenSe Fund:
Dach, Leslie, science associate.
Highland, Joseph, Ph. D., director, Toxic Chemicals Program.
Johnson, Anita, staff attorney.
General Accounting Office, Human Resources Division:
Ahart, Gregory J., Director.
Jojokian, Albert B., Assistant Director.
Linz, James, Supervisory Auditor.
Health, Education, and Welfare Department:
Baier, Edward J., Deputy Director, National Institute for Occupational
Safety and Health, Center for Disease Control
Cooper, Richard, Chief Counsel, Food and Drug Administration, Public
Health Service.
Fraumeni, Joseph, Jr., M.D., Chief Environmental Epidemiology Branch,
Division of Cancer Cause and Prevention, National Cancer Institute,
National Institutues of Health.
Griesemer, Richard A., D.V.M., Ph. D., Associate Director for Carcino-
genesis Testing Program, Division of Cancer Cause and Prevention,
National Cancer Institute, National Institutes of Health.
Kennedy, Hon. Donald, Ph. D., Commissioner, Food and Drug Adminis-
tration, Public Health Service.
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VI
ORGANIZATIONS REPRESENTED AT HEARINGS-Continued
Health, Education, and Welfare Department-Continued
Page, Norbert P., D.V.M., Chief, Priorities and Research Analysis Branch,
Division of Criteria Documentation and Standards Development, National
Institute for Occupational Safety and Health, Center for Disease Control.
Roberts, Howard R., Ph. D.~ Director, Bureau of Foods, Food and Drug
Administration, Public Health Service.
Scheuplein, Robert J., Ph. D., Chief, Dermal and Ocular Toxicity Branch,
Division of Toxicity, Bureau of Foods, Food and Drug Administration,
Public Health Service.
Upton, Arthur C., M.D., Director, National Cancer Institute, National
Institutes of Health.
Thermo Electron Corp., David H. Fine, Ph. D., senior scientist.
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CANCER-CAUSING CHEMICALS
Safety of Cosmetics and Hair Dyes
MONDAY, JANUARY 23, 1978
hOUSE OF RFIPRESENTATWES,
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGA!flONS,
Co1~MrrrEE ON INTERSTATE ANI) FoREIGN COMMERCE,
- WclAslthigton, D.C.
The subcommittee met, pursuant to notice, at 10 a.m. in room
2141, Rayburn House Office Building, Hon. John E. Moss (chairman)
presiding.
Mr. Moss. The committee will be in order.
I am pleased today to open this set of hearings on cancer-causing
agents in the environment. Last year our subcommittee held related
hearings on carcinogenic flame-retardant chemicals, including Tris,
a chemical found in children's sleepwear. At that time, I noted that
evidence continued to accumulate indicating that the vast majority of
cancer is caused by environmental factors. Unfortunately, this evi-
dence continues to accumulate. It is my hope that, during this set of
hearings, we will learn more about the sources of cancer~causing chemi-
cals and what action needs to be taken to eIimin~te consumer exposure
to them.
This Nation took a major step toward the conquest of cancer in
December 1971, when the National Cancer Act was signed into law.
At that time a new era began, one which was designed to find and
eliminate the sources of cancer.
The importance of eliminating sources of cancer cannot be over-
stated. The final report of the national panel of cancer cOnsultants
published in 1971 stated:
Cancer is the No. 1 health concern of the American people. Of the 200 million
Americans alive today, 50 million will develop cancer at present rates of incidence,
and 34 million will die of this painful and often ugly disease if better methods
of prevention and treatment are not disoovered.
In 1974, about 345,000 lives were lost to cancer; $1.8 billion was
spent on hospital care for cancer; and patients and society lost 1.8
million work-years due to this disease. In May of this year, I stated
that I believed "the cancer plan established in 1971 to vigorously
pursue all avenues toward ending cancer in our lifetine appears to
be floundering." I still believe this is trüe~
During the 94th Congress, this subcommittee examined examples of
industrial sources and occupational exposure to carcinogens. Several
days of hearings weye held ln Washington and Newark, N.J., dn this
(1)
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2
topic.' During the 95th Congress we held hearings in Cincinnati,2
Ohio, to examine the problem of organic chemical contamination of
drinking water, particularly contamination of Ohio River drinking
water by the toxic chemical, carbon tetrachloride. We also have re-
viewed the adequacy of existing laws in protecting the public from
exposure to toxic flame-retardant chemicals in the environment.~
Today we expect to examine several aspects of the National Cancer
Institute's efforts to discover the sources of cancer.
NOl's research program in the area of environmental causes of
cancer centers around its bioassay testing program. Chemicals are
selected for carcinogenicity testing if NCI believes they are potentially
dangerous and may be inhaled, ingested, or absorbed.
Budget and manpower restrictions have limited the number of
chemicals that can be tested; and although over 700 new chemicals are
developed each year and there are 3.5 million chemicals now in exist-
ence, Qnly 437 chemicals are now part of this program. Since NCI
places only 60 chemicals a year "on test" in this program, it would
take decades for it to test the approximately 1,800 chemicals now on
the NIOSH suspected carcinogens list.
There are several links in the chain that must function properly for
this program to be effective. They include:
One, proper monitoring of the entire universe of chemicals for po-
tentially dangerous substances;
Two, effective management of the chemical carcinogenesis testing
program;
Three, the timely dissemination of the program's findings to appro-
priate regulator agencies; and
Four, utilization of these findings by the regulatory agencies.
We will carefully examine these links today.
In order to gain a more inrdepth understanding of thes~ issues, we
will focus our attention upon potentially carcinogenic ingredients in
hair dyes and the production and use of the industrial chemical 1 ,~
dichloroethane.
Recently, the subcommittee was informed by NCI that several
ingredients in hair dyes besides 2,4 diaminoanisole are carcinogenic.
If this is true, consumers utilizing hair dye products containing these
ingredients may be facing an unnecessary risk of cancer. During the
second and third days of these hearings, we hope to explore this ques-
tion indepth since more than 25 million Americans may be at risk.
We welcome Dr. Arthur Upton, Director of the National Cancer
Institute and Mr. Edward J. Baier, Deputy Director of the National
Institute for Occupational Safety and Health to discuss these impor-
tant matters with us.
I understand that Congressman Maguire would like to be recog-
nized at this point. Mr. Maguire?
Mr. MAGiYIRIc. Thank you, Mr. Chairman.
A former Acting Director of the National Cancer Institute stated
in 1977 that most cancers are theoretically preventable if we identify
I "Enviromne,it~l Causes of Cancer," hearings held by the Subcommittee on Oversight and Investiga
tions, Committee On Interstate and Foreign Commerce, May 28 and Sept. 20, 1976-serial No. 94-14i.
"CarbOn Tetraajiloride Contamination of Public Drinking Water," hearings held by the Subcommittee
on Oversight and Investigations, Committee on Interstate and Foreign Commerce, Apr. 13, i977-serlal.
No. 95-29.
"Regulation of Cancer-Causing Flame.Retardant Chemicals and Governmental Coordination of Test.
ing of Toxic Chemicals," hearings held by the Subcommittee on Oversight and Investigations, Committee
on Interstate and Foreign Commerce, May ii, 13, and i6, 1977-serial No. 95-33. -
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3
causative agent~, avoid exposure to them, and eliminate them from
the environment Other experts, including a number of outstanding
cancer research scientists, have gone sO far as to indicate that 60 to 90
percent of human cancers result from exposure to environmental
carcinogens.
Nobel Laureate Dr. James Watson concluded as early as 1975, "It
makes most sense, rather than striving for early detection; to spend
most of this National Cancer Institute money to see that known
environmental carcinogens are kept away from the American public
But such a goal will bring NOT into direct conflict with very powerful
industrial lobbies. And at least when I was on the National Cancer
Advisory Board there was a noted reluctance for the NOT to take on
any regulatory role."
In view of the recognized significance of environmental factors in
the causation of c~ancer, it is distressing to realize how limited a pro-
portion of the NOT cancer program budget is directed toward efforts
to limit our exposure to these substances. Why is this so?
Any attempt to reduce the exposure of the American public to
carcinogenic substances must rely quite heavily on testing procedures
designed to measure their carcinogenicity. This testing system should
function in such a way that it can deal effectively with both the
potentially dangerous materials currently in use and the large number
of new substances being introduced in one form or another every yeI~r.
The carcinogenesis testing program of the NOT has the responsibility
for testing substances for their potential carcinogenicity. The per-
formance of the program to date is gi'ossly inadequate~
For example, it has been stated that NOT currently has the capacity
for placing 60 new substances on test annually. This number is wholly
inadequate in view of the estimated 1,800 suspected carc nogens listed
by the National Institute for Occupational Safety and Health and the
approximately400 new cOmpounds entering the environment annually,
some of which may be carcinogenic.
In addition, available evidence indicates that the test system is
functioning well below the stated capacity. Why is this so?
A major snag in the testing system occurs at the level of reporting.
For reasons that are~ not clear to ~ne, reports of positive carcinogenic
findings move amazingly slowly through the clearinghouse process
Consequently, there is a delay in the dissemination of this vital
information to the appropriate regulatory agencies, resulting in the
prolongation of our exposur~ to the toxic effects of the chemicals.
What can be done to improve the efficiency of the system? Why is
there a problem with reporting test results?
Since the inception of the National Cancer Institute in 1937, the
Congress has voted for steadily increasing appropriations. This
reflects the concern of this country about the increasing death toll
from this dreaded disease. And, because of the numbers involved,
one might even call it a ~plague. In New Jersey, my home State, we
have the highest toll of all.
The depth of our Nation's concern about the extent of cancer was
demonstrated quite vividly in our willingness to embrace the concept
of the so-called "War on Cancer" in 1971 However, it appears that
6 years and billions of dollars lat~r, little has changed neither in
research emphasis nor in cancer's grip on America's lives.
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4
The time has come for us to take a hard look at where we are and
what direction we should take in the fight against cancer Has this
money-now over $800 million a year-been wasted? Or has a sig-
nificant portion of it been wasted? Are lives being saved? Can we do
better? These are the vital questions we must address in these hearings.
Thank you very much, Mr. Chairman.
Mr. Moss. At this time the Chair will call the first witnesses:
Dr. Arthur Upton, Director of the National Cancer Institute. He
is accompanied by Dr. Richard A. Griesemer, Associate Director
for Carcinogenesis Testing Program, and Dr. Joseph Fraumeni,
Chief, Environmental Epidemiology Branch, Division of Cancer
Cause and Prevention.
Gentlemen, will you come forward. At this time the Chair will
administer the oath to the witnesses.
Dr. Upton, will each of the persons accompanying you give
testimony?
Dr. UPTON. Yes, sir.
Mr. Moss. Do you solemnly swear that the testimony you are
about to give this subcommittee shall be the truth, the whole truth,
and nothing but the truth, so help you God?
Dr. UPTON. I do.
Dr. GRIESEMER. I do.
Dr. FRAUMENI. I do. /
Mr. Moss. Doctor, we are pleased to welcome you.
TESTIMONY OP ARTHUR C. UPTON, M.D., DIRECTOR, NATIONAL
CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH, DE
PARTMENT OP HEALTH, EDUCATION, AND WELFARE, ACCOM-
PANIED. BY RICHARD A. GRIESEMER, D.V.M., PH. D., ASSOCIATE
DIREC~rOR FOR CARCINOGENESIS TESTING PROGRAM, DIVISION
OP CANCER CAUSE AND PREVENTION; AND JOSEPH PRAUMENI,
JR., M.D., CHIEP, ENVIRONMENTAL EPIDEMIOLOGY BRANCH,
DIVISION OP CANCER CAUSE AND PREVENTION
Dr. UPTON. Thank you, Mr. Chairman.
My name is Arthur Upton. I am the Director of the National Can-
cer Institute.
Mr. Chairman and members of the subcommittee, I am honored
to appear before you today to present the activities of. the National
Cancer Institute as they relate to the cause and prevention of cancer.
Appearing with me to answer questions are two members of my staff,
Dr. Richard Griesemer, Associate Director for Carcinogenesis Test-
ing, and Dr. Joseph Frai~meni, Chief of the Exivironmental Epi-
demiology Branch.
With the support, dedication, and commitment of the Congress,
the President, and the people, we have been able since 1971 to mount
a comprehensive nationwide program of research, demonstration, and
education on cancer. The goal of the national cancer program is to
develop the means to recbice the toll of cancer in man which despite
significant advances in research is a major health problem whose im-
pact has been slowly but constantly increasing over the past 50 years.
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5
Cause and prevention research has one of our highest priorities
because prevention offers the best hope for ultimate control of cancer
Our greatest involvement in this area is in environmental carcino-
genesis, due to the increasing evidence, that a majority of cancers are
environmentally related.
Scientists do not agree comp1etely on which factors. in the environ-
ment may increase human risk to cancer. There is general agreement
that cigarette smoking has contributed to about 40~ percent of cancers
in men in the United States, and to a lower, although increasing,
percentage of cancers in women. This large segment of the cancer
burden consists mainly of lung cancer, but also includes cancers of
the throat, esophagus, bladder, and pancreas.
Efforts in cause and prevention to understand the origins of human
cancer are reflected by a spectrum of research approaches First we
are studying ~known carcinogens, such as radiation-including ultra-
violet light-tobacco, and chemicals such `as drugs and hormones.
Second, we are supporting animal studies to screen chemicals for
carcinogenic potential At the same time, we also are emphasizing
research to improve these testing procedures At the present time,
approximately 90 chemicals are being tested in animals. Experiments
on an additional 64 chemicals are being analyzed and reports are
being prepared Another 100 chemicals will be started on. test this
year The testing is managed and directly supervised by the National
cancer Institute with support from a prime con.tractor~ Tracor Jitco
Third, we have expanded efforts to identify patterns of the occur-
rence of cancer in our population as it relates to the environment
These activities include followup of NCI's cancer mapping studies
which include efforts to identify population groups at high risk of
cancer, through community and, occupational studies, as well as by an
examination of the effects of drugs, hormones, and radiation Other
studies examine the role of nutrition in susceptibility to cancer. Fourth,
we support research on the basic mechanisms of how normal cells
become ca~cero'us.
The solutions to the many problems involved in the prevention of
the 100 or more forms of cancer will not come rapidly or easily. Many
scientists believe that cancer is. the result of a complex interaction of
cellular events, with hereditary information, chemical agents, radia-
tion, and viruses all playing a role in one or another instance
The problem of the role of chemicals in cancer is by itself immense
Estimates of the number of chemicals in the world exceed 7 million
and the chemical abstracts registry now lists 4,500,000 different
entries Relatively few of these chemicals have been tested for car~
cinogenicitry in animals Some 16,000 reports of animal experiments of
various sorts have been published Most of them are not definitive,
but some evidence for earcmogenicity has been established in animals
for about 400 chemicals. ` `
Even fewer chemicals have been established as carcinogens for
humans-roughly 30 to 35, depending on the criteria used. These
chemicals that are carcinogenic for man also are carcinogenic for
animals with two exceptions-arsenic and benzene, which we believe
have not yet been adeqnately teated in animals.,
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6
Each animal experiment requires about 4 years and costs about
$300,000. Together with limited laboratory facilities and a shortage
of personnel trained to conduct animal tests for carcinogenicity, the
Nation's capacity for carcinogenesis testing is severely limited. The
presently available resources for carcinogenesis testing in the world
are estimated to permit testing of between 200 and 500 chemicals per
year.
It should be emphasized that even if all chemicals could be tested
for carcinogenicity, only a small portion of the problem would be solved
To predict the risk to man from known animal carcinogens, one also
must know something about the dose levels that are carcinogenic,
the relative poten~cy of the carcinogen, the routes of exposure to which
man is~susceptible, and the relative ability of human `tissues to detox-
ify, metabolize, and excrete carcinogens. Moreover, man rarely is
exposed to large doses of single carcinogens. Instead, man usually is
exposed `intermittently to smaller doses of many carcinogens. Two
or more carcinogens acting in combination may be mutually inhibitory,
additive, or multiplicative in their effects. This reflects in part the
fact that there are different kinds of carcinogens, some of which act
largely to promote the cancer-inducing effects of others.
Chemical testing by the National Institutes of Health-primarily
the National Cancer Institute-began as a research effort and was
expanded to its current level largely as a demonstration and feasibility
study to develop means to fill the perceived' Federal needs. Among
HEW agencies, the Food and Drug Administration, the National
InstitutO for Occupational Safety and Health, the National Institute
of Environmental Health Sciences, and the National Cancer Institute
all conduct some chemical-testing activities. The National Cancer
Institute studies constitute the majority of these. It is noteworthy in
this connection that cancer is only one of the health impacts of chem-
ical exposure. The state of the art for testing other long-term health
effects is as yet similarly primitive.
We believe that the role of Government will need to change over
the next `decade, from one of providing major support for chronic
toxicity testing to one of primary concern with the development and
validation of nOw test methods and quality control of testing con-
ducted by industry. For the interim, we are concerned that allocating
resources to expand our testing program may occur at the expense
of research needed to improve testing methods. It is of major impor-
tance that the role of the NCI-and of HEW-in chemical testing
be critically examined within the context of the needs and respon-
sibilities of the various regulatory agencies.
The NCI animal bioassay effort for chemical carcinogens can
merely detect a chemical's potential for causing cancer in humans.
Its results' cannot tell us whether a particular chemical will cause
human cancer, hut' they may alert us to a presumptive risk and thus
serve as a basis for further studies of the chemical in question.
As a screening method, the bioassay consists of administration of
a single chemical at two dose ~1eve1s to rodents of two species and both
sexes. Rodent species are used for the screening process beôause of
their relatively short lifespans, their well-understood biological
behavior, and the high rate of correlation between rodent carcinogen-
PAGENO="0013"
7
icity and the small number of known human carcinogens. In the
interest of tosting as large a; niiniber of chemicals as is economically
feasible, a given chemical is usually given to only 50 animals of each
sex and species at each dOse level. Because of the small number of
animals tested and theirbrief lifetimes as compared to that Of humans,
one of the dose levels is set as high as possible to maximize the chance
that a carcinogen will not go through tha; screen undetected.
For this same reason, the route of administration for the chemical
is selected to permit exposure of as many body organs as possible.
Each animal test requires about 4 years, including design, adminis-
tration of the chemical, and analysis of the results.
Because of the cost of these experiments, both in time and dollars,
chemical selection is a critical part of the testing process, At the
present time, selection depends on information concerning extent of
human exposure as well as what is known concerning the biological
effects of a given chemical and any other similar chemical. Production
data, information on dispersion into the environment, chemical
structure, and mutagenicity data, for example, are examined by a
chemical selection working group composed of scientists from NOT
and 10 other Federal agencies. This group nominates chemicals for
testing. Their nominations then go to a chemical selection subgroup
of the Clearinghouse on Environmental Carcinogens, a chartered
advisory body of non-Government members that meets in open
session to make recommendations to NOT.
Additional information on chemicals selected for testing comes to
NOT as a result of these discussions, and the final decision to test is
made by NOT staff.
Similar review procedures with other clearinghouse subgroups con-
cerned with experimental design and data evaluation provide review
of the testing protocol and results After review, the institute publishes
a report of the findings, announced in the Federal Register, and in-
forn~is the public via the media.
Copies of the report are sent. to other Federal agencies. Additional
information on some chemicals alsO is sent to physicians concerned
with occupational medicine, industrial and labor organizations, and
environmental and consumer groups. S
In addition to the clearinghouse activitiCs, the National Cancer
Institute is represented on a number of interagency committees con-
cerned with Federal activities in environmental toxicology. It is
noteworthy that the four principal regulatory agencies-Food and
Drug Administration, Environmental Protection Agency, Consumer
Product Safety Commission, and Occupational Safety and Health
Administration-have recently formed an interagency regulatory
liaison group for the purpose of coordinating and pooling their re-
sources and activities in the area of environmental toxicology. They
have also made overtures to NOT, NIEHS, and NIOSH to join them
in a common approach to problems of mutual interest~
NIEHS has a growing interest in the development of test methods
for mutagenicity and teratogenicity, as well as for other toxicity
indicators. NOl and NIEHS are cooperating in the development of
a program aimed at testing the animals in the cancer bioassay program
for other toxicities. When fully operational, this will greatly increase
PAGENO="0014"
8
the benefit derived from the NOT bioassay program. Thus, to a sig-
nificant degree, the NOT and NIEHS are embarked on an extension
of testing, from carcinogenicity to a whole range of toxic effects.
My colleagues and I shall be pleased to answer any questions.
Mr. Chairman, this concludes my statement.
Mr. Moss. Thank you, Doctor.
At this time, the chair recognizes the gentleman from New Jersey,
Mr. Maguire.
Mr. MAGUIRE. Thank you, Mr. Chairman.
At the outset T want to say that T am gratified with the approach
that Dr. Upton has taken at NOT since he was appointed to this very
important position. But we do have a serious problem of past perfor-
mance and of emphasis.
Just to highlight a bit more of what T think the problem is, I would
like to point out that in July 1977, NOT promised this subcommittee
that 119 final reports on cancer-causing substances would be completed
by January 1, 1978. In fact, earlier in the year a promise of 230
reports have been made
However, as of January 1, 1978, only 20 final reports have actually
been made available.
Doctor, why is the number of completed tests and completed
reports so far below what we were promised?
Dr. UPTON. Mr. Maguire, may T refer that question please to
Dr. Griesemer, who is in charge of the testing program?
Mr. MAGIJIRE. As you wish.
Dr. GRIESEMER. Mr. Maguire, we have reached about 80 percent
of our goal in analyzing and reporting the results of some experiments
with some 200 chemicals.
T should go back to explain to the committee that a great many
experiments were started at about the same time as recorded on the
chart on the wall. Tn 1974 and 1975, the majority of those experi-
ments were completed in animals at about the same time. That does
not complete the experiment, however; because the animals then are
sacrificed, and the pathologists have to analyze the tissues--
Mr. MAGUIR1D. Presumably, Doctor, all of that was known when
these estimates were made. Everybody knew what the process was.
Yet, if you look at that graph on the wall, you find a total of 20-
the red line out at the right-hand side of January 1978, as opposed
to the 119 that was promised the subcommittee and the 230-the
green line at the top-that was earlier promised.
[The graph referred to follows:]
PAGENO="0015"
9
Graph of Final Reports Compared to Projected
Reports by the National Cancer Institute
Number of Final Reports
240
220
200
180
160
140
120
100
80
60
40
20
0
NUMBER OF
FINAL REPORTS ~ ~20 *
~NoA~OoRTi, V~A 119
FINAL REPORTS -
PROMISED I HEW L
230
Final Reports Promised to
Labor4lEW Appràpriations
Subcommittee by 111fl8
March July January
1977 1977 1978
*Of a total of 437 chemicals in Bioassay Program
Jan. 16, 1978
PAGENO="0016"
10
Dr. GRIESEMER. Let me adjdress the numbers, if I may.
Mr. MAGUIRE. Everybody knew what. the process was; presumably
the projections were made in full knowledge of what the process was.
Yet, we get--that isn't anything like an 80-percent performance;
that's less than 10 percent.
Dr. GRIESEMER. As of today, we have completed experiments on
92 chemicals. These have been submitted for publication and referred
to the Clearinghouse on Environmental Carcinogens. We have 68
additional chemicals in draft form where the material has been col-
lated ai~d~, on those that are positive, transmitted to the regulatory
agencies. This is a total of 160 out of 201 chemicals in the backlog of
chemicals on which we are working.
Of the remaining-
Mr. MAGUIRE. On the final report-4he final report is not available
on most of those. And a final report is the only thing on the basis of
which action can be taken. Therefore, as long as test results are being
analyzed and draft reports are being circulated, people are still at
hazard. Is that not correct?
Dr. GRIESEMER. I believe you are referring to printed reports on
which we do not put our emphasis. It is most important that the
information about the potential carcinogenicity of chemicals be
reported to the public and to the regulatory agencies as fast as possible.
In order to do that, we have concentrated on compiling the informa-
tion. As I said, we have done that now on 160 chemicals. That inf or-
mation has been transmitted to regulatory agencies. Of the 40 re-
maining chemicals, there are problems in quality assurance which
require additional review; and those will be out in the next, several
months.
Mr. MAGUIRE. My understanding, though, is that regulatory
agencies-at least this is what they tell us-feel unable to act on the
basis of a draft report. As long as that is true, the public is at jeopardy.
Dr. GRIESEMER. What we call our final report is the one on which
92 have now been completed. It takes several more months for them
to be printed and published. But that is not an important factor in
this process because the information has been transmitted to every-
one long before the printing process. So we have concentrated not
on-
Mr. MAGUIRE. Does the public know about this-
Dr. GRIESEMER. Yes; these studies are all dispatched openly-
Mr. MAGUIRE. Prior to the final report being prepared?
DR. GRIESEMER. Yes; they are discussed openly in public forum.
Mr. MAGtYIRE. Of course, even when we get final reports, as we did
with hair dyes, we get them about 100 years after the first knowledge
that scientists had that there was a problem of carcinogenicity with
hair dyes. And at least since 1955, as I understand it, we have had
test data that confirm those suspicions of 100 years ago. Yet, now
finally, 2 years after the work was completed, we are beginning to
get some action.
What are we going to do about that problem of the timelag during
which people are exposed to cancer?
Dr. GRIESEMER. No one is more aware of the need to protect the
public than we, Mr. Maguire.
PAGENO="0017"
11
At present there is no timelag. Several years ago there was.
Mr. MAGUIRE. So, these gaps in that chart are going to disappear.
Is that what you are saying.
Dr. GRIESEMER. Those gaps are not real. The real numbers are
that 160 out of 201 have been repGrted already. The others are nearly
finished.
So, aside from the few that require review pathology, all of theni
will have been reported in the next several months.
Mr. MAGUIRE. I think that is a very optimistic reading of the facts.
Thank you, Mr. Chairman.
Mr. Moss. The time of the gentleman has expired.
The Chair recognizes the gentleman from Pennsylvania, Mr. Marks.
Mr. MARKS. Thank you, Mr. Chairman.
Dr. Upton, I am wondering if you, sir, and/or the other gentlemen,
believe that there should be a single Federal policy for identifying and
regulating carcinogens? Or should we continue on the path that
we have been where agencies such as FDA and EPA and the rest
formulate their own respective policies?
Dr. UPTON. Mr. Marks, I believe there ought to be a single Federal
policy~ I have been very much encouraged m the short time I have
been at the National Cancer Institute to see the development of a
coordinated and concerted effort in this direction.
Mr. MARKS. What has been done? I noted in your statement there
seems to be a voluntary coming together, but nothing very serious.
Dr. UPTON. The four major regulatory agencies-Consumer Prod-
uct Safety Commission, Environmental Protection Agency, FDA,
and OSHA-have agreed to meet regularly. The heads of the agencies
meet regularly in what is known as the Interagency Regulatory Liaison
Group. They are now undertaking a joint review of research needs
and research resources relating to the whole `atea of .eiivironmental
toxicology.
Mr. MARKS. Doctor, I must assume that this is being done on a
voluntary basis.
Dr. UPTON. To my knowledge, that is correct.
The four agencies-known colloquially as the Council of Four-
have invited the National Cancer Institute, the National Institute of.
Environmental Health Sciences, and the National Institute on Occu-
pational Safety and Health to meet with them to review jointly our
efforts and our perception of need in this same domain, environmental
toxicology.
Mr. MARKS. What has ~been the response from these agencies,
lncludinE NOT?
Dr. UPTON. We were overjoyed to have such a meeting just before
Christmas and have undertaken to assemble all of our data that
relate to activities in environmental toxicology and to arr~y our data
in the same format as has been selected by the Council of Four.
I would hope that within another week or two, we can report our
information to them and that shortly thereafter it will be possible for
another meeting at which research agencies and the regulatory agen-
cies can sit down together and see what the needs of the Nation are
and how the agencies can best work together to form a common policy
to address those needs.
24-600 0 - 78 - 2
PAGENO="0018"
12
I can assure you that I feel deeply convinced that this problem area
is an enormous one and that NOT must intensify its efforts in this area.
Without the liaison and the coordination that may be possible through
the meeting that I referred to, the Council of Four, long-range plan-
ning on our part would be very difficult.
So, I see this as a very important step toward the constructive
and realistic and adequate planning that we must make and the
programing that we must accomplish if we are to serve the Nation
well in this area of need.
Mr. MARKS. What about the other agencies that have been invited
to join? Has their response been the same?
Dr. UPTON. At the meeting I attended there were indeed repre-
sentatives from NIEHS and NIOSH. I detect no disinclination to be
- involved in this common effort.
Mr. MARKS. You are answering it in the negative by saying that
you see no disinclination. Was it affirmative? Did they agree that
there are difficulties in doing this, but we are going to do it?
Dr. UPTON. It was affirmative; yes, sir.
Mr. MARKS. What have been some of the difficulties in bringing
this about before this t~ime? And what are the difficulties as you see
them now?
Dr. UPTON. I confess to you that 1 don't have an adequate knowl-
edge of the history. I came to the National Cancer Institute in
August, and my experience dates from that time.
I think what we have witnessed over the last decade or more in
this problem area is a growing awareness o. need. I think that until
the relatFv~eIy recent past, although it had been recognized that there
were hazards in the environment-carcinogenic hazards-the evidence
that these might be important in low-dose levels, levels of the sort to
which the population is exposed, had not been widely recognized or
accepted. There is still, as you know, controversy as to the nature
of the dose response relationship. But I think, with evidence from
quantitative epidemiological studies of irradiated populations and of
some populations exposed to chemicals of various kinds, there has
been less and less willingness to assume the existence of so-called
safe tolerance or threshold levels, and more concern about the possible
combined effects of small quantities of materials in our environment.
This has spurred growing concern and, naturally, growing effort
to deal with this problem.
I think that what we are seeing is probably the dawn of a new era,
if you will, in the assessment of cost versus benefit, the degree to
which it is necessary or desirable for society to regulate the substances
which it adds to its food supply, the water it drinks, the environment
in which it lives.
I think to most of us regulation is unwholesome, undesirable. We
don't want someone telling us what we must or must not do. On the
other hand, to the extend that we are all prisoners of the environ-
ment, we want to know the facts; and we want to arrive at societal
policies that aire acceptable in terms of the risk they entail to all of us.
As we have emphasized, I think the existing methodology to arrive
at these assessments is still crude. Again, until recently, I don't think
many scientists would have advocated the expenditure of colossal
amounts of money, colossal numbers of man-years, to routine testing
PAGENO="0019"
in mice or rats. The tests themselves are limited in what information
they can provide to us.
With growing concern about the environment, obviously some
scaling-up of the:effort is called for.
Mr MARKS Doctor, obviously one of the problems involved ~n
iegulating carcinogens seems to be the probleni of identifying them
The animal feeding studies are not only very costly but are time-
consuming.
What efforts have you undertaken to develop screening tests that
are reliable, fast, and inexpensive?
Dr. UPTON. At the present time, about half of the total dollar invest-
ment in our bioassay program, which, at the present time, amounts
to roughly $23 million per annum overall, about half of that amount
is going into the refinement of test methodologies leading to improved
short~tèrm. tests as well as improved understanding of the interpreta-
tion of long-term tests..
Perhaps Dr. Griesemer would like 1~o expand on this, if you wish
more information.
Mr~ MARKS. if he can rather quickly. I think our time is almost up.
Mr. Moss. The Chair will permit Dr. Griesemer to complete the
answer.
Dr. ORIESEMER. Thank you. It is obvious that we cannot test all
of the chemicals that need to be tested. We have a concerted effort
to find alternatives, including the battery of short-term assays that
you have alluded to~
Mr. Moss. Does that answer the gentleman's question?
Mr. MARKS. Yes.
Mr. Moss. The Chair recognizes the gentleman from Pennsylvania,
Mr. Waigren.
Mr. WALGREN. Thank you, Mr. Chairman.
In answer to the las~t question, was it said that $23- -
Dr UPTON $23 million per year is the current budget for our bio-
assay program, roughly one-half of which is devoted to refinement in
test methodology.
Mr. WALGREN. So, we are spending $11.5 million to improve testing.
Dr. UPTON. At the present time, that is correct.
Mr. WALOREN. And to try to develop methods that would be more
convincing or more direct.
Dr. UPTON. That. is the sum allocated within the bioassay program.
I think it is only proper to point out that much~ o~ the ancillary
research in the Institute is dedicated to an understanding of the cancer
process itself, out of which I think it can be expected that new knowl-
edge will lead to improvements in test procedures.
Within, the bioassay program itself the effort at test refinement is
funded at roughly $12 million per year.
Mr. WALGREN. The bioassay program is one program of several
programs that you are conducting?
Dr. UPTON. That is correct.
Mr. WALGREN. What amounts are resez~ved for &ttempts to improve
testing validity in the other programs?
Dr. UPTON. The other programs do not devote themselves directly
to testing. So, sums are not earmarked in the other budgets for test
reflnement as such But in many of the other programs that concern
the mechanism of carcinogenesis-studies on. the action of chemicals,
PAGENO="0020"
14
how chemicals are metabolized, how they react with sites in target
cells, how the cells then behave and evolve into malignant growth-
these. kinds of studies can ultimately be expected to provide informa-
tion that will lead to improved tests in the bioassay program.
Mr. WALOREN. So, there is no budgetary ~way to see whether an
increased effort is being made to develop more convincing testing
methods.
Dr. UPTON. I think there is such a method. I think it would require
a detailed analysis of all of the activities in the carcinogenesis program
area. This would be possible. We have not attempted to do this to
date. It could be done. It is not beyond doing.
Mr. WALGREN. I am sort of interested in that because, on an insti-
tutional basis,_when the public does not believe the test, then the
political will isIost~t~ implement the perhaps-needed remedy and, to
the degree that the public is not prepared in this country even to
accept other countries' tests on rats, to convince them to change our
1ifesty1e~. I would be very interested to know what your Institute is
doing to try to either improve the convincing power of those tests-
that is a very critical function you have. I would hope that there
would be a way to get at it budgetarily to see that an effort is being
made in that direction.
I wanted to go back to what I took to be the thrust of Mr. Maguire's
questions. It has to do with the difficulty that regulatory agencies
have in being reluctant to rely on nonfinal reports as to the danger
of these substances. It takes so long apparently to get these reports
into a final form.
Mr. Maguire's thrust on the subject was that the reports are not
yet in final form.
Do I understand that there is a final report on this substance that
is known as 1,2 dichloroethane?
Dr. GKIESEMER. Yes, there is a final report; I brought a copy with
me.
Mr.' WALGREN. And-
Dr. GRIESEMER. Final in the sense that it has been interpreted and
validated by NOT.
Mr. WALGREN. Has that report been published?
Dr. GRIESEMER. No. It will be submitted for publication today. It
will appear at the clearinghouse meeting on March 6 for open review.
Mr. WALGREN. You say it will be submitted for-.
Dr. GRIEs~iER. For publication as a technical report by the
Natioiial Cancer Institute.
Mr. WALGREN. And then where is that disseminated?
Dr. GRIESEMER. We have a mailing list of several thousand who
receive the report. It is also announced in the Federal Register, as
available from the National Cancer Institute.
Mr. WALGREN. I see.
And do you expect them to receive that imminently?
Dr. GRIESEMER. It takes perhaps 1 to 2 months for the printing
process and the announcement in the Federal Register.
Mr. WALOREN. Now, do I understand that the draft report on this
compound was completed in March of 1974?
Dr. GRIESEMER. No, that is not correct.
Mr. WALOREN. When was the draft report on this compound
completed?
PAGENO="0021"
15
`Dr. GRIESEMER. The draft report was completed last week.
The NCI's validation and interpretation was completed last week.
Mr. WALóRi~x. All right-
Mr. Moss. Will the gentleman yield?
Mr. WALGEEN. Yes.
Mr. Moss. I believe the gentleman was addressing himself to the
completion date for the animal studies rather than the preliminary
report.
And if Dr. Griesemer would address himself in responding to the
date of the completion of the animal studies.
Dr. GKIESEMER. The animal study for 1,2 dichloroethane in the
mouse was completed in April of 1974 and for, the rat in May of 1974.
Mr. WALGREN. Looking at that time from April-May of 1974 to the
completion of the preliminary report last week, what happened in that
time?
Dr. GRIESEMER. Ordinarily it would take perhaps 6 or 8 months to
analyze the data and write a report. One should have expected a report
within a year. I do not know why my predecessors did not do that.
The analysis in this case began after November of 1977, when a team
of people was put together to address this.problem.
Mr. WALGREN. And there is no indication in the files whatsoever
why that apparently went silent for that period of time?
Dr. GRIESEMER. Well, it, along with the other 200 chemical experi-
ments, were not analyzed and reported during about a 2-year period.
There are indications in the files of why that may have been. But,
since I was not here, I do not really know the answer to your question.
Mr. WA'LGREN. What are the indications in the file?
Dr. GRIEsE~ii~R. There apparently was a lack of an adequate
number of staff people to address this issue. Also, no one had ever
attempted to analyze a large number of experiments before. So,
methods and groups of people had to be assembled. Methods had to
be developed' for this purpose. The NCI did recognize that respon-
sibility and created the carcinogenesis testing program operationally
in July of 1977.
It has only been in the last 15 or 18 months that attention has been
given to this problem of numbers of chemical experiments that were
uncompleted. , .
Mr. WALGREN. Well, I am not talking about numbers of uncom-
pleted; I am talking about these particular results. , Apparently,
there was indication that there was potential harm. It was put in a
file that then lay dormant.
Dr. GRIESEMER. That's correct.
Mr. WALGREN. Can you address the same concern as to the
chemicals in hair dyes? Have they lain dormant?:
Dr. GRIESEMER. Yes, they were part of the large group of experi-
ments that were uncompleted. I ~have the dates. on each of the in-
dividual hair dyes so far as when the animals were killed, if you wish.
But in general they were around 1974 and 1975.
Mr. WALGREN. I would think that perha,~s we ought to hold the
record open there for whatever could be submitted on the date-
Mr. Moss. Without objection, we will hold the record. We will
have the gentleman get together with staff to more precisely define.
his request. And then we will ask that the agency submit the specific
data requested.
[The following table was received for the record:]
PAGENO="0022"
Date Date Date Date
Last Pathology Pathology Draft
Chemical Sacrifice Completed Confirmed Report
N-phenyl-p-phenylenediamine 12/74 10/20/76 10/10/77 11/77
2-nitro-p-phenylenediamine 8/74 5/75 In review
p-phenylenediamine HCL 2/76 4/77 In review
4-nitro-o-phenylenediamine 10/75 9/76 In review
1-phenyl-3-methyl-5-pyrazole 4/76 12/76 In review -- -
2,5-toluenediamine sulfate 2/75 7/76 4/77 7/77
4-amino-2-nitrophenol 8/76 12/76 1/78 Est. 2/78
2,4-diaminoanisole sulfate 4/75 7/76 8/17 10/77
Direct Black 38 8/77 1/78 1/78 Est. 2/78
Direct Blue 6 8/77 1/78 1/78 Est. 2/78
Resorcinol** 12/72 9/73
2,4_toluenediamine* 6/72 7/73 12/77
m_phenylenediamine* 3/72 7/73 12/77
* Not standard bioassay but exploratory studies
** Not standard bioassay, skin painting study.
PAGENO="0023"
17
Mr. Moss. The Chair recognizes the gentleman from Tennessee,
Mr. Gore.
Mr. GORE. Thank you, Mr. Chairman.
Dr. Griesemer, you said that the printing process would take 1
to 2 months. Does that include the approval and review that you
also mentioned?
Dr. GRIESEMER. No; that is just the printing process itself~
Mr. GORE. flow much does the approval and review take?
Dr. GRIE5EMER. On the average, it takes 5 months for the quality
assurance program and the NCI staff review.
Mr. GORE. At what stage is this report you say that you have
brought with you-you said that it is ready to be submitted?
Dr. GRIESEMER. It is completed by NCI and is ready to go to the
printers.
Mr. GORE. Oh, I thought it had to go to the review board.
Dr. GRIESEMER. It will, but it will also go to the National Clearing~
house on Environmental Carcinogens, for scientific review. They will
assess the adequacy of the study and NCI's interpretations. But, in
general, that does not affect the printing process.
Mr. GORE. I see. So, the public and the scientific community will
have this report in their hands late next month?
Dr. GRIESEMER. Whenever it's printed; yes.
It will be made publik~, obviously, on March 6. The regulatory
agencies have already received copies.
Mr. Moss. Would the gentleman yield?
I think this record is now becoming somewhat obfuscated by state-
ments made here that tern! to make very unclear the nature of a
final report.
Now, a final report is not issued, is it, until such time as the review
process is completed?
Dr. GRIESEMER. If thé~Iearinghouse were to find substantial
differences which-
Mr. Moss. You can answer it ~yes or no, can't you?
It is not* a final report until that clearing process is completed. Is
that correct?
Dr. GRIESEMER. That is incorrect.
Mr. Moss. All right; you go ahead. then and correot us.
Dr. GRIESEMER. It is a final report when we have completed our
review.
Mr. Moss. Well, that's exactly what I said: Until the review is
completed, it is not a final report.
Dr. GRIESEMER. The cl~.aringhouse is an advisory ~om~nittce-~--
Mr. Moss. Do you ever revise a report after clearinghouse
procedure?
Dr. GRTESEMER. Rarely.
Mr. Moss. Do you ever?
Dr. GRIESEMER. No. We incorporate their suggestions--'
Mr. Moss. Could 7ou?
Dr. GRIESEMER. As a looseleaf in the report-
Mr. Moss~ Could you? .
Dr. GRIESEMER. We could reprint a copy if necessary.
Mr. Moss. And you say there has never been a revision following
that-the review procedure.
PAGENO="0024"
18
Dr. GRIESEMER. To my knowledge, there has not been a revision.
Mr. Moss. And how comprehensive is your knowledge? Because
staff tells me to the contrary.
Dr. GRTESEMER. I have attended all the meetings.
Mr. Moss. All the meetings for how long?
Dr. GRIESEMER. All the meetings of the clearinghouse for review
of our final reports.
Mr. Moss. For how long?
t'r. GRIE5EMER. During the last year.
Mr. Moss. Did it only come into being during the last year?
Dr. GRIESEMER. Yes. The clearinghouse began in December of 1976.
Mr. Moss. As soon as you are finished, Mr. Gore, we will have the
spelling out of the procedure step by step so that we know actually
what constitutes a final report upon which a regulatory agency may
rely.
Mr~ GORE. I think the significance of this cannot be overstated
really. Our job is not to make you uncomfortable at the witness table
but to find out why the job has not been done that should have been
done. It is of such overriding importance because of the goal that we
all want to reach, and that is combating cancer as effectively as pos-
sible.
It seems from the testimony that there is a lot of buckpassing going
on somewhere. You are attempting to say that the final report does
not have any significance. Yet, when we had the Tris hearings, the
Consumer Product Safety Commission came up here and said, "We
have to wait until the final report comes in. We can't do anything on
a draft." The chairman just got this letter from the Environmental
Protection Agency on ethylene dichloride. He encloses NCI's findings.
The Environment'~il Protection Agency says, "Please note that it
is a draft." OSHA responds to another inquiry from the subcommittee,
"A complete written report on these experiments was still in draft
stages."
That makes it very easy, you see, for these other agencies to pass
the buck. They say, "Well, it's still a draft."
If you were in one of those agencies, would you advise them to
go to court on the basis of a draft before the final report was available?
Dr. GRIE5EMER. The regulatory agency requires validated data.
The answer to your question is a lengthy one. Mr. Chairman, I
would be happy to address it when you wish.
Mr. Moss. If the gentleman from Tennessee desires it.
Mr. GORE. Maybe it's not fair to ask you for a yes-or-no answer
to that. I think the answer is no. If I were in a regulatory agency and
I were confronted with a decision tç go to court or not-go to court
and there was a draft report and NCI said, "Well, we'll have the
final report soon; it will just be a few more months, 5 or 6 more
months. The studies have been completed, but maybe a few years
from now we'll get a final report."
You know, it puts them in a position where there is the bureaucratic
disease of passing the buck and waiting until all the ducks are in a
row. I mean, that dynamic just naturally takes over, it seems to me;
that seems obvious. There is the fact that only 20 final reports have
been done when you said that 200 would be done by this date. I think
that fact still stands.
PAGENO="0025"
19
You can. talk. all you want to about the significance of having com~
pleted drafts for so many of them. But the fact i~ you did not meet
your goals. The fact is that the importance of meeting those goals is
something that cannot be overestimated.
We are just trying to see what can be done to speed that process up.
I do not want a lengthy answer to the earlier question, but please
comment on that if you would.
Dr. GRIESEMER. We are attempting to act responsibly in trans-
mitting, this very important information to the public as rapidly as
is obtained. It is necessary that the information be scientifically
accurate as well as transmitted rapidly.
The process involved starts back at the very beginning; that agencies
know which chemicals we're testing. They tell us which ones they are
interested in. We endeavor, at their request to keep them supplied
with information on the progress of the experiments. Hence, the
draft reports, telephone calls, many kinds of communications.
At the time we have validated the results and analyzed them, we
notify the regulatory agencies that that is our final interpretation.
It is possible for them then to take regulatory actions.
We do not believe that they should wait for a printed copy which
takes several more months-~--
Mr. `GoRE. They do.
.Dr. GRIESEMER. The information is not changed from the draft to
the printed copy.
Mr. GORE. They do; they believe they~ should wait until the final
report apparently; at least. that's what t~iey tell us.
The public is facing the danger of cancer caused by substances put
into the environment so long as there is no action taken. Now, you
pass the buck to them; they pass the buck back to you. We are over-
seeing that process, trying to improve it. And I do not think it's the
most helpful thing to say., "Well, they should act on the basis of a
draft report." The fact of the matter is they should have a final report
as quickly as is humanly possible.
Dr. GRIESEMER. They are getting the completed NOl report as fast
as is humanly possible, then it becomes their responsibility to act, not
ours.
Mr. GORE. You said, Dr. Upton, that, with growing concern about
the environmental causes of cancer, some scaling-up may be called for.
It seems to me that there is more than growing concern. It seems to
me-well, I have been told that the consensus among scientists today
is that somewhere between 60 and 85 percent of all the cancer that is
discovered in people is caused by substances that are put into the
environment as a result of man's activity. Yet, only 20 percent of your
budget is oriented toward those kinds of' causes of cancer.
Shouldn't more money out of your budget be directed toward seek-
lngout and preventing environmental causes of cancer?
Dr. UPTON. Mr. Gore, I could not agree `with you more. I think
that this is, as I strove to emphasize, an area on which we are seeking
to place greater emphasis. We are, I think, constrained in science to
achieve an equitable balance between the opportunities that exist in
the research area and the need that may exist for progress in that area.
Clearly, from my testimony, from the tenor of remarks this morning,
PAGENO="0026"
20
I think we all agree that there needs to be more emphasis on the as-
sessment of risk associated with the environment.
Since I have come to NCI, I have taken some steps to mount several
reviews of this problem area so that we can determine what the op-
portunities are and how best to exploit them.
In the area of testing, I think it is safe to say that the degree to
which the NCI budget should go into the application of routine tests
as opposed to the refinement of test methodology is a moot question.
Traditionally, the National Cancer Institute has viewed itself as a
research organization, `not one that should devote its energies and
resources to routine applications.
We do have, by virtue of chronological developments, the largest
single bioassay program in existence. Dr. Griesemer has told me that
he thinks that we could increase our numbers of compounds being
tested to 100 within the near future if we could put some more money
into the program; but that 100 a year might come close to saturating
the available resources within the country. I have told him that I
would like to move and saturate those resources, move to 100 this
year if we can so do.
Mr. GORE. Let me put that answer in the context that I think it
should be viewed in. The Chemical Abstracts Registry now lists
about 4.5 million chemicals that are in use to4ay. Only 1,600 have
been tested; 400 suggest some carcinogenicity in animals.
Now, if 100 per year is going to saturate the process, then we need
to dramatically change the process.
Dr. UPTON. I think that is one of the most serious issues we face:
How many should we be testing as a Nation. It is this question that
we are trying to address with the council Of four, with NIOSH, with
NIERS. We are trying to develop a plan to equip the Nation to do the
testing on the scale that needs to be done.
Mr. Moss. The Chair recognizes the gentleman from California,
Mr. Waxman.
Mr. WAXMAN. Thank you, Mr. Chairman.
Dr. Upton, I understand your institute has discovered that some
of the chemicals used in hair dyes are carcinogenic. Is that correct?
Dr. UPTON. Tests in the rodent systems have indicated carcino-
genicity at high-dose levels; that is correct.
Mr. WAXMAN. Again, we have information that another commonly
used product may cause cancer. When I go back home and talk to
people in my district I find that they feel ,fru~trated ançl confused
about the war on cancer. I hear people say that they worry about
cancer like they do about muggers: There's nothing they can do
about either. Now, you are a scientist. You've studied cancer. Your
institute is a leader in the war on cancer.
Should people avoid using chemical products that contain carcino-
gens? Will it make any difference?
Dr. UPTON. Mr. Waxman, I think it is a misconception that every-
thing causes cancer. I think with growing numbers of agents that
have been shown to produce cancers in animals there is a tendency
to throw up one's hands and say, "Everything is carcinogenic; it's
hopeless." But I think that is not the case.
PAGENO="0027"
21
I think the record of experimentation with rodent systems discloses
that~ the majority of substances are not carcinogenic at high dose
levels in the standard test procedure.
It turns out that the compounds that we have been reporting on
were selected in advance by cancer investigators because they were
suspect to begin with.
Mr. WAXMAN; Dr. Upton, I am not saying that people are con-
cerned that everything causes cancer. It is just that when they hear
another announcement from the National Cancer Institute or some
other governmental agency that something causes cancer-~-particu-
larly if it is something they have been using for years-they adopt the
attitude, "Well, if I'm going to get cancer, I'm going to get cancer;
I might just as well continue dyeing my hair, using saccharin, or
smoking cigarettes."
If pepple stop using a hazardous product that they have used for
years, will it have any positive effect on their health? Or is it something
that they ought to be very fatalistic about and continue to use?
Dr. UPTON. If we take the cigarette anak~gy, I think evidence sug-
gests that cessation of smoking reduces risk. So that, if there is a lesson
there, I think the lesson is that we can help ourselves by avoiding
exposure or continuation of exposure to agents that cause cancer.
Mr. WAXMAN. In other words, you are saying that people who have
smoked cigarettes and stopped have a reduced risk of lung cancer
than those who continue sornoking?
Dr. UPTON. That is correct.
Mr. WAXMAN. The assumption would be that those who stop using
hair dyes containing chemical carcinogens may well reduce the risk of
getting cancer. Is that correct?
Dr. UPTON. My expectation would be that the eventual risk of
developing the disease will be related to the total accumulated dose
of the carcinogen; if one ceases exposure, one stops accumulating dose,
and to that degree stops accumulating increased risk.
Unfortunately, as we have tried to emphasize, our knowledge of
these problems is still rudimentary. So, it is not possible for us to
quantify' risk estimates.
Mr. WAXMAN. But we do know that chemicals that are carcinogenic
may well and probably do-either by themselves or in combination
with other carcinogens-cause cancer somewhere down the line, 10,
15, 20 years from now. Is that correct?
Dr. UPTON. This possibility cannot be excluded. There is a pre-
sumption of risk.
Mr. WAXMAN. So, isn't it prudent for people to stop using products
when they find out that they contain carcinogens which may increase
their risk of cancer?
Dr. UPTON. Yes, sir. I would say that it is prudent. I' think that
,the decision frequently devolves upon the individual. If there is a
perceived benefit associated with a certain practice, there may be a
presumptive risk; and the individual h~s to attempt for himself or
herself to weigh the risk and benefit. When it is a product that goes
into foodstuffs that everyone eats off the shelf of the grocery store,.
it is more difficult to allow the individual to exercise that kind of-
PAGENO="0028"
22
Mr. WAXMAN. Do you think there is any kind of benefit to be
derived from hair dyes that contain carcinogens? There are other
products, I assume, on the market that can be used.
Dr. UPTON. That is the crux of the matter: Are there safe alterna-
tives? If there are, then most people, I suppose, would opt for the
safer alternative. But, if there are not-we use radiation in medical
practice. We know that radiation can cause cancer. We do not know
categorically that the small doses of radiation involved in a chest
X-ray increase the risk of cancer, but we can't exclude that possibility.
So, we think it is prudent to minimize such radiation.
Mr. WAXMAN. But there's a situation where there is a benefit.
Dr. UPTON. There is clearly in that situation a benefit. We try
to titrate benefit against risk, keeping the risk always a small as
possible.
I think the same analogy will be carried over into chemicals of
various kinds, drugs, food processing agents, and so on.
Mr. WAXMAN, But the point that I hear over and over again-
and I really feel it is important to have this clarified for people-is
that, if they do avoid products with carcinogens in them, they have
a chance to avoid getting cancer. Continuing to use those products
greatly increases the risk of cancer. Even if consumers have used this
products extensively in the past, isn't it prudent for them to discon-
tinue their use?
Dr. UPTON. That is correct.
Mr. WAXMAN. This is a frustration I think people have because
they keep hearing about new discoveries that some commonly used
chemicals are dangerous. They hear about it, and they start assuming
that either everything is going to cause cancer or that the risk is ex-
aggerated. If we ask people to be prudent in their own use of products,
don't we in government have a responsibility to encourage a market-
place free from carcinogens?
Dr. UPTON. I would think so.
Mr. WAXMA.N. A very important part of the war on cancer, as I
see it, is prevention. It is as important-and maybe even more impor-
tant-as trying to find a cure. Certainly trying to prevent cancer has
got to~ be a high priority.
Dr. UPTON. I would think that is correct. We need to have the
facts. We need then to arrive at prudent evaluation sand socially
acceptable policies.
Mr. WAXMAN. Do you have any ideas how we can improve our
credibility when we tell people that there is a dangerous sustance in
the marketplace and that, in using that substance or that chemical or
that product, they increase their chances of getting cancer?
It seems to me the Government has lost a tremendous amount of
credibility. People sort of throw up their hands and say, "Oh, another
warning from some government bureaucrat," They don't take Gov-
ernment warnings seriously. This is particularly disturbing to me
because one out of four people in this country will get cancer; that's
a terrifying figure.
Do you have any thoughts on that?
Dr. UPTON. It is an immense problem. I think that ultimately it
devolves on education, ur~derstanding as much as one can know
about the facts today, about how one can go from the facts as we see
PAGENO="0029"
28
them to the development of prudent lifestyles and `prudent policies.
What is prudent for one person may not necessarily be acceptable to
the next. So, there' will have to ~be some open discussion, some ex-
change of dissenting points of view.
Unfortunately, today the science of the matter is not cut and dIy.
There are honest scientific differences of opinion about evidence and
how one can interpret it.
Mr. WAXMAN, Thank you very much. You have been very helpful.
Mr. Moss. The gentleman's time has expired. The Chair recognizes
the gentleman from Ohio, Mr. Luken.
Mr. LUKEN. Thank you, Mr. Chairman.
Dr. Upton, 1 just arrived and do not have any extensive questions.
I am wondering about something that occurs to the general public.
When talking about hair dyes, and processed foods, water pollutants,
and air pollutants that are part of our industralized society, do you
come to the conclusion that cancer is, per se, more prevalent in this
kind of environment than in a more natural environment without
such exposure?
Dr UPTON The data for rates of cancer in American women-if we
discount the changes that we can attribute to cigarette smoking-do
not suggest an increasing risk, despite the fact that we have industri-
alized, But it is complicated. The rate of stomach cancer has gone
down dramatically. -
I think that the answer to your question, at the present time, can
only be couched very tentatively. We do know from studies in animals
from some epidemiological evidence, occupational groups, that some
of the agents that you refer to, products of an industrial age, can
increase the risk of cancer. So, one would suppose that, everything
else being the same, if the population were systematically exposed to
those agents willy-nilly, the effects would be an increase in the risk of
cancer. -
As I say, with industrialization-
Mr LUKEN But don't we have statistics, don't we have surveys?
Dr. `UPTON. The incidence of stomach cancer has come down
dramatically, I would like to ask Dr. Fraumeni if he would be willing
to speak to these questions because he is'an epidemiologist who' has
followed the data very, closely.
Dr. FRAUMENI. I would say that, for a great many cancers-and
by this I mean some of the major cancers that affect people in the.
United States and in Western countries-the rates are much higher
than they are in underdeveloped countries. I think that we can
attribute this to various aspects of modern civilization such as cigar-
ette smoking, dietary factors, occupational exposures, certain drugs,
and the like.
Mr. LUKEN. That is conclusive in your opinion.
Dr. FRAUMENI. I would think so.
Mr. LUKEN. Then `we had better be about the business of controlling
it. ` -
Dr. FRAUMENT. Identifying and contreiling.
Mr. LUKEN. Dr. Upton, about the NOT bioassay program testing
for potential carcinogenicity of hair dye ingredients: I would like to
refer you to and introduce into the record a subcommittee letter to
PAGENO="0030"
24
NCI dated May 21, 1977 and an NCI letter to the subcommittee
dated June 21, 1977. You are being furnished a copy of that now.
Mr. Moss. The Chair asks unanimous consent that the letter
referred to by the gentleman from Ohio, Mr. Luken, together with
the response from NCI, be included in the record at this point.
Is there objection? Hearing none, such will be the order of the
coramittee.
[The correspondence referred to follows:]
CONGRESS OF THE UNITED STATES,
HOUSE OF REPRESENT4TIVES,
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS OF' THE
COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE,
Washington, D.C., May ~1, 1977.
Dr. Guy R. NEWELL,
Acting Director, National Cancer Institute,
National Institutes of Health, Bethesda, Md.
DISAR DR. NEWELL: The Subcommittee on Oversight and Investigations has
been conducting inquiries into governmental actions to protect the public from
exposure to potentially dailgerous chemicals. We are particularly interested in
tests how in progress on chemicals in consumer products.
We would appreciate your response to the following inquiries concerning the
poteittial hazards of hair dyes and hair dye constituents:
1. What tests are now underway involving hair dyes or hair dye constituents?
2. When will these tests be completed?
3. If any tests were completed, what were the results?
4. Has NCI made any calculations as to the size of the population at risk?
5. What additional hair dyes or hair dye constituents will NCI be testing in the
future?
6. Does NCI have all the information it needs to properly test for the safety of
commercially produced hair dyes?
If ~ny reports on the potential carcinogenicity of hair dyes or hair dye constit-
uents have been completed or are in draft form, the Subcommittee requests that
these reports be forwarded to it.
If you have any questions concerning these requests, please contact Lester
Brown at (202) 225-5365.
We would appreciate your response to these inquiries by June 10, 1977. Thank
you tor your cooperation.
Sincerely,
JOHN E. Moss,
Chairman.
DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE,
PUBLIC HEALTH SERVICE,
NATIONAL INSTITUTES OF HEALTH,
Bethesda, Md., .Iune ~1, 1977.
Hon. JOHN E. Moss,
Chairman, Subcommittee on Oversight and Investigations, Committee on Interstate
and Foreign Commerce, House of Representatives, Washington, D.C.
DEAR MR. CHAIRMAN: This letter is in response to your inquiry of May 21
addressed to Dr. Guy R. Newell regarding hair dyes and hair dye constituents.
Question No. 1: The following chemicals identified as hair dyes, hair dye coit-
stituents, or related materials, are presently being tested for carcinogenicity
in the .Carcinogenesis Bioassay Program, Division of Cancer Cause and Preiien-
tion, National Cancer Institute:
4-Amino-2-Nitrophenol Phenyl-3-Methoxypyrazolone
0-Anisidine-Hydrochloride M-Phenylendiamine Dihydrochloride
4-Chloro-0-Phenylendiamine 0-Phenylendiamine Dihydrochloride
2,4-Diaminoanisole P-Phenylendiamine Dihydrochloride
P-Diaminobenzene P-Phenyleiidiamine, N-Phenyl,
Diaminonitrobenzene Hydrochloride
4-Methyl-M-Phenyldiamine Resorcin
4-Nitro-0-Phenylene Diamine P-Tolylendiamine Sulfate
4-Methoxyaniline Hydrochloride
PAGENO="0031"
25
Question No. 2: The animal treatment phase of the studies has been completed
and technical reports should be available in nbout eight months.
Question No. 3: The outcome of the experiments is not yet known because the
data and information generated in these experiments has not been verified A
summary of available data, the Experimental Design Status Report (EDSR)
and the Individual Animal Pathology Report (Table II) are being forwarded
under separate cover.
Question No. 4: The, size of the population exposed to hair dyes, hair dye
components and related materials has to the best of our knowledge not been
determined.
Question No. 5: In the future other hair dyes will be considered for carcino-
genesis testing along with other environmental chemicals. The limited resources
for testing necessitates that selection of chemicals and setting priorities for their
testing be accomplished, through the due processes of the Chemical Selection
Working Group.
Question No. 6: The objective of bioassay testing as presently performed in
our program is primarily to determine the carcinogenic potential of chemicals
iii animals. Further toxicology testing for general human safety evaluation is
presently the requirement of the regulatory agencies and the manufacturers
Additional studies, such as the penetration of the skin by the chemicals, will
probably be required.
I hope this information will prove useful.
Sincerely yours,
SIDNEY SIEGEL, Ph.D.,
Coordinator, Injorrnaiion Activities, Carcinogen Bioassay and
Program Resources Branch, Carcinogenesis Program, DCCP.
Mr. LUKEN. Are you familiar with the document?
Dr. UPTON. I do not think I have seen it before, Mr. Luken.
Mr. LUKEN. Is it something you could refer to quickly?
Dr. UPTON. Yes, sir.
Mr LUKEN On that date, the subcommittee wrote inquiring about
the testing of hair dye ingredieuts. In your return letter, you stated
that NOl was testing some 16 hair dye ingredients and related ma-
terials. Why were these particular materials selected?
Dr. UPTON. Mr. Luken, may I refer that question to Dr. Griesemer?
Mr. LUKEN. Yes.
Dr. GRIESEMER. These were selected from among the universe of
chemicals on a itumber of bases, including human exposure or evidence
related to human exposure, such as the production rates. Second, it
was on the basis of suspected biological effects such as toxicity or
mutagenicity: the same- criteria that are applied tO all the chemicals
in the test.
Mr. LUKEN. Are they part of a family or a class then?
Dr. GRIESEM~R. There is a use category, -but there also are some
subcategories of chemicals within the use category.
Mr. LUKEN. Is there a commou structure in these groups of chem-
icals which is suspicious?
Dr. GRIESEMER.. We tend to select representative chemical -types
and those with the greatest production among a long list of chemicals,
some 162 hair dye ingredients and related chemicals. Obviously we
cannot test them all; so we selected chemical examples.
Mr. LUKEN. To date you have annouticed that there are two hajr
dye ingredients-2,4-diaminoanisole suif ate and 2,4-toluenediamine-
that are careinogemc in animals under NOl tests However, in vitro
mutagenicity tests - on hair dye and hair dye ingredients suggest
several other ingredients may be potent mutagens and potential
carcinogens; right? -
PAGENO="0032"
26
Dr. GRIESEMER. Correct.
Mr. LUKEN. Do you believe there is some correlation between this
mutagenicity-especially considering the Ames test results-and car-
cinogenicity?
Dr. GRIESEMER. Yes. In this category of chemicals the relationship
between mutagenicity and carcinogenicity is very close. So that if a
chemical is mutagenic it would make us very suspicious.
Mr. LUKEN. In your opinion then mutagens are, in and of them-
selves, dangerous?
Dr. GRIE5EMER. Yes.
Mr. LUKEN. Is there a significant difference of opinion on that in
the literature?
Dr. GRIESEMER. I do not believe so. Mutagens are hazardous.
Mr. LUKEN. There is no difference of opinion as. to whether or not
they are hazardous; but is there as to the degree of hazard?
Dr. GRIESEMEE. There is some indecision about prediètability
of carcinogenicity from knowledge of mutagenicity.
Mr. LUKEN. Could you discuss that a little bit?
Dr. GRIE5EMER. In some of the major published studies, the
association between mutagenicity and carcinogenicity is on the order
of 85 or 90 percent; that is a good correlation. However, not all
classes of chemicals have been tested for mutagenicity. Certainly
not many for carcinogenicity. And there are some classes of chemicals
where the association is very poor-in the metals, for example. So,
we cannot use mutagenicity data alone to establish the carcino.-
genicity of chemicals.
They still have to be either tested in animals or one has to determine
their carcinogenicity for man by epidemiologic studies.
Mr. LUKEN. What is the Ames test?
Dr. GRIESEMER. That is a ba~terial test for mutagenicity.
Mr. LUKEN. What is your opinion as to the validity of the Ames test?
Dr. GRIESEMER. It is a good test for mutagenicity and, in some
chemical classes, is a strong indicator of possible carcinogenicity.
Mr, LUKEN. Some chemical classes?
Dr. GRIESEMER. Yes. Those in which the hair dyes fall, there
appears to be a good correlation.
Mr. LUKEN. I have no further questions.
Mr. Moss. The gentleman's time has expired. The Chair recognizes
the gentleman from New Jersey, Mr. Binaldo.
Mr. RINALDO. Thank you very much, Mr. Chairman. Doctor, it
has been estimated, I understand, that 90 percent of cancer is caused
by environmental factors. Would you agree or disagree with that
statement, and could you tell me why?
Dr. UPTON. I am acquainted with that estimate. I could not dis-
pute it. It is based largely on comparison of rates of cancer at dif-
ferent organ sites in various parts of the world.
The difference between those parts of the world with the highest
incidence of cancer at a given site and those parts of the world with
the lowest incidence may vary by a factor of as much as 50. If one
averages over all sites of the body the overall differences between
high regions and low regions, if the differences are related to the
environment and not genetic factors, then perhaps up to 90 percent
of cancers are environmentally related.
PAGENO="0033"
27
Mr. RIxALDO. In other words, you say that there is a certain amount
of truth to the statement that about 90 percent of the cancer in this
country could be caused by environmental causes, and the other 10
percent by nonenvironmental causes or factors?
Dr. UPTON. That is correct.
Mr. RINALDO. If we get down to the percentage of cancer that is
caused by environmental factors in the United States, could you
give me some estimate of how that would break down, for example,
smoking, the so-called western diet-the way we eat, not the specific
chemicals in the food-and exposure to chemicals in consumer prod~
ucts?
Dr. UPTON. Mr. Rinaldo, may I refer that question to Dr. Frau-
meni?
Mr. RINALDO. Yes.
Dr. FRAUMENI. Mr. Rinaldo, it has been estimated that perhaps
40 percent of cancers in American men are related to cigarette smok-
ing. In American women, it is on the order of. 15 percent. For occupa-
tional exposures, the estimates ar~ a little uncertain; but they probably
are on the order of 10 percent or under in men.
Medicinal exposures, such as exogenous estrogens used for treat~
ment of menopausal symptoms, contribute perhaps on the order of
5 p~ercent and probably less.
Dietary exposures appear to be extremely important. The esti-
mates here are vague because there is a great deal of research going
on now to try to identify the specific nutritional constituents and
mechanisms that are responsible. But there is much indirect circum-
stantial evidence to suggest that nutritional factors account for a
sizable percentage of cancers in both sexes.
Mr. RINALDO. We still did not get down to the exposure to chemicals
in consumer products. You only gave two sets of statistics there. You
started out with statistics pertaining to smoking: 40 percent in males
and 15 percent in females But what would you say would be the
total, if you add exposure to chemicals in consumer products? Could
you give some percentage for that?
Dr. FRAUMENI. I do not think we can.. We are lacking the epidemio-
logic information at this point to estimate the contribution of this
class of chemicals. I think some may speculate on a range, but I do
not know with any precision what that range is. I think we just need
to step up our research in epidemiology-and in experimental studies-
to try to detect the specific carcinogenic hazards involved.
Mr. RINALDO. You state you don't know what the range is. But if
we take smoking, diet, alcohol, maybe automobile emissions and
exhaust from trucks and engines, sunlight and other radiation, air
contamination, maybe water contamination, occupational exposure
to chemicals, and the other factors, such as drugs, which you said
amounted to under. 5 percent, and~* then subtract that from 100,
shouldn't we come up with some idea very simply of what it is?
Dr. FRAUMENL I am not sure what you mean by consumer products.
Mr. RINALDO. I think I have pretty much run the gamut.
Dr. FRAUMENI. If you are talking about chemical carcinogens, I
would say that these account for the bulk of human cancer; there is
no question in my mind about that.
24-600 0 - 78 - 3
PAGENO="0034"
28
Mr. RINALDO. Let me rephrase your answer. Are you stating that
chemical carcinogens account for the bulk of cancer as a result of
chemical carcinogens in consumer products?
Dr. FRAUMENI. Chemical carcinogens may be represented by a
dietary factor, a tobacco constituent, an occupational agent, or other
exposures. I think all would fall into the class of chemical carcinogens.
Mr. RINALD0. But I still want to take it a step further. Let's elim-
inate smoking and diet. Then we come up with chemical carcinogens
in other consumer products. Now, when you get down to that residue,
what range would you attribute to that particular group?
Dr. FRATJMENL I would be guessing.
Mr. RINALDO. I would be interested in hearing your educated guess.
If you have 40 percent, for example, in the male due to smoking
and 10 percent from occupational exposure to chemicals, 5 percent
for other causes; we are up to 55. What percentage would you say
is caused by the diet? You mention that as being extremely important.
Dr. FRAUMENI. I think it is a large percentage.
Mr. RINALDO. We are up to 55. The largest it could be is 45.
Dr. FRAUMENI. I must point out that the percentages are going to
go well over 100 percent. For many tumors we are dealing with inter-
actions between environmental agents such as occupational exposure
in combination with tobacco. So, to try to bring it up to* 100 percent,
I think, would be unreasonable at this stage of knowledge.
Mr. RINALDO. Because it is caused from more than
Dr. FRAUMENI. It is caused from combinations of agents.
Mr. RINALDO. I understand that. But don't you think we can get
this down to the point where we can get some fairly reasonable range
for this. I am trying to isolate the exposure to chemicals in consumer
products as differentiated from alcoholic beverages, the diet, and
cigarette smoking.
Dr. FRAUMENL I am not sure we can at this time. I think our knowl-
edge is still incomplete from an epidemiologic standpoint.
Mr. RINALDO. Do you believe that animal feeding studies which ex-
pose rats, mice, and other animals to large amounts of a substance
over a short period of time have consensus support in the scientific
community for predicting carcinogenicity in human beings?
Dr. UPTON. I think that the majority of workers in carcinogenesis
accept the association between carcinogenic effects in animals and
carcinogenic effects in humans. So, I think the majority of workers
would accept the evidence as a basis for the assumption of presump-
tive risk, given carcinogenic effects in an animal test, high doses, short-
or long-term exposure. This, then, constitutes a presumptive basis
for presumptive risk in man.
Mr. RINALDO. Would this be your response to the argument that
animal bioassays give the animals doses so high that they may induce
cancer because it overwhelms detoxification mechanisms which pro-
tect humans from the smaller doses that we meet in real life?
Dr. UPTON. That is one of the uncertainties: Whether, if the same
agent were encountered in humans over a longperiod of `time, because
the dose is smaller and because the human differs in metabolic capa-
bilities, the outcome would be different. We simply do not know now.
Mr. RINALDO., The uncertainties are apparently overwhelming.
Dr. UPTON. The uncertainties are overwhelming at this stage.
PAGENO="0035"
29
Mr. RINALDO. What is your total budget?
Dr. UPTON. This year we are budgeted around $872 million.
Mr. RINALDO. In light of all these uncertainties and the failure to
give even broad ranges and estimates and the difficulty you have in
answering some of these questions, could you tell me what percentage
of that $872 million is going to new tests?
Dr. UPTON. A very small percentage of the total budget. You
mentioned that at the present time $12 million is being devoted to
testing as such. We have decided to increase the rate of testing in the
coming year so as to essentially exploit totally the existing capability.
Clearly, this is a very small step toward a very large problem. I would
not contend that this is an adequate step. I think it is as much as we
can do at this moment because the resources are limited.
Obviously, the Nation needs a critical look at the problem area and
a plan which deals in an adequate and socially acceptable, socially
responsible manner. We are working with the other research agencies-
NIERS, NIOSH-and with the regulatory agencies to arrive at an
assessment of need and a coordinated plan.
Mr. RINALDO. For the record, Dr. Upton, I would like you to submit
what plans NOT has for increasing the amount of your budget that
will be going to new tests.
Dr. UPTON. I would be happy to do that.
Mr. Moss. Without objection, the record will be held open at this
point to receive that material.
[The following information was received for the record.]
CosTs To ExPLoIT EXISTING CAPABILITY
The standardized animal carcinogenicity testing capacity presently available in
U S laboratories would permit up to 120 chemicals to be placed on test each year
Current NCI contract levels of testing involve placing approximately 60 chemicals
on testper year with a particular chemical remaining on test for approximately 3
years. To increase NCI levels of testing to 120 chemicaLs per year will require
annual increases in funding of approximately $6 mfflion over a 3-year period, at
which point funding will st~bihze The1 present $12 million testing cost would rise
to about $18 million in FY 1979, to $2~ million in FY 1980, and to $30 million in
FY 1981. At that point the present long-term testing capacity would be saturated
with 360 chemicals on test (120 annual).
Mr. Moss. The chair is concerned over the fact that I do not know
what a final report is; or, if I understand what it is alleged to be, then
I am puzzled as to why we have a review procedure that takes place
on the scientific accuracy of it after it has been fihalized and printed.
I have in my hand here a report "Bioassay of 1,2 dichioroethane
for possible carcinogemcity, second draft for DEG review, October 13,
1977." Underneath that is written in your handwriting, I believe,
Dr. Griesemer, "unverified."
Is this the draft report that is circulated to the regulatory agencies?
Dr. GRIESEMER. No.
Mr. Moss. This is not the draft report.
What would that be? Would it be a final draft?
Dr. GRIESEMER. Yes.
Mr. Moss. And would bear "final draft" on its cover?
Dr. GnIE5EMER. It says "final draft" or "camera ready" and is
accompanied by a cover letter that identifies it as having been verified.
PAGENO="0036"
30
I might point out that the draft in your hand may very well have
been sent to whoever requested it, either under freedom of information
or through intergovernmental channels.
Mr. Moss. Well, it may have been. Let us then narrow down who
routinely wou]d receive it outside of the agency itself.
Dr. GRIE5EMER. Yes. At the time our draft is completed and is
now a -final draft-
Mr. Moss. No; I want to know who had received the second draft.
Dr. GRIESEMER. I have no idea who might have received a second
draft. Whoever requested it.
Mr. Moss. We have no set routine then for distribution of the
second draft.
All right. Following this draft, a final draft is prepared.
Dr. GRIESEMER. Yes.
Mr. Moss. And reviewed within the agency for accuracy.
Dr. - GRIE5EMER. Yes.
Mr. Moss. And that goes to scientific accuracy as well.
Dr. GRIESEMER. Yes.
Mr. Moss. Then it is a final report and is printed; is that correct?
Dr. GRIESEMER. Yes.
Mr. Moss. It then goes to the review group, the advisory group.
Dr. GRIESEMER. Before printing, a copy of the same material that
goes to the printer's goes to regulatory agencies and to the clearing-
house-
Mr. Moss. Let's just stay with what I am talking about.
Dr. GRIESEMER. The final printed copy is distributed through the
announcement in the Federal Register.
Mr. Moss. Now, does that occur before or after review by the
advisory commit1~ee?
Dr. GRIESEMER. After.
Mr. Moss. All right, let's get back to the period before the review
by the advisory committee. What is the distribution at that point?
You have a printed report-
Dr. GRIESEMER. To the regulatory agencies and to the clearing-
house members.
Mr. Moss. And is it sent to them as a final report?
Dr. GREISEMER. Yes.
Mr. Moss. Without any caveat that they should be alert to any
possible changes that might occur as a result of the review procedure?
Dr. GRIESEMEE. No; no caveats.
Mr. Moss. All right, what is the value of the review procedure?
Dr. GRIESEMEE. It first serves to review the entire process in
public so that, if mistakes are ma~de, they will be recognized and can
still be corrected.
Mr. Moss. Wouldn't a prudent operation call for that kind of
review before and not after publication and distribution?
Dr. GRIESEMER. The only reason we do not do it that way is the
very urgent need to inform the regulatory agencies of the findings of
the study.
Mr. Moss. The urgent need to inform them, even though it might
be incorrect.
Dr. GRIESEMER. The data will not change; only the interpretation
might change.
PAGENO="0037"
31
Mr. Moss. The data will not `change. Then: why the review after
the publication?
Let me say, Doctor, that I am well in my 26th year here; and I
cannot think of anyone else that prepares a document in its final form
and distributes it and then reviews it, It makes no sense to this
member.
Dr. GRIESEMER. Again, Mr. Chairman, the reason for submitting,
for sending the regulatory agencies the material that we have is for
reguiatory purp9sos to protect the public.
Mr. Moss, Then that requires that it be extremely accurate, as
accurate as humanly possible; doesn't it?
Dr. GRIESEMER. That is correct.
Mr. Moss. Therefore, why should you be less prudent in making
certain that it is accurate for them than you are for the general public?
Dr. GRIEsEMEI~. I'm sorry. I don't understand the question.
Mr. Moss. Well, I don't understand the review. And I am trying
to get it in some rational context. Why does the review occur after
publication?
Dr. GRIESEMER. The primary purpose of the review is for a public
hearing.
Mr. Moss. If it has any value, why doesn't it occur before publica-
tion?
Dr. GRIESEMER. Because we feel it most important that the data
be transmitted in order to protect the public. If one waits a month
or two for not only that review but many other reviews that take
place after our data is released, then people may be unnecessarily
exposed to hazardous' chemicals.
Mr. Moss. Why do you have the review at the stage where it
occurs?
Dr. GRIESEMER. Primarily for a ~public hearing and partly to
assure the staff that their review has been adequate. And that has
been the case-
Mr. Moss. Then, in context with an ` earlier response you gave
me when we had our first discussion of this, that you know of no
instance of a change as a result of the review, who don't we eliminate
the review? Either that or have it occur before publication.
Dr. GRIESEMER. That is under consideration at present.
Mr. Moss. Well then, I strongly urge that it either be made mean-
ingful or that it be eliminated. And I think we will be able to. have a
consensus on that when the committee writes its report.
It does not seem worth while to me at all.
On the matter of the projected final reports, how many final reports
in the group under discussion last March have now been completed?
Dr. GRIESEMER. Ninety-two.
Mr. Moss, Ninety-two final reports. That means they have been
published?
Dr. GRIESEMER. Twenty have, been published. and 20 have been
submitted to the open literature. So, about 40 have reached the
publication stage. .
Mr. Moss. Put in literature for what purpose? .
Dr. GRIESEMER. For the scientific community.
Mr. Moss. For the scientific review, the review within-
PAGENO="0038"
32
Dr. GRIESEMEB. No; not the review. They have been submitted to
biomedical journals for publication rather than published in a technical
report series.
Mr. Moss. Well, at what point in publication do they become a
final report? Is it not~published in the Federal Register?
Dr. GRIESEMER. The answer to that-publication in the Federal
Register-is 20.
Mr. Moss. Well, then you have 20 fiuial reports.
You were not the one who testified-I think it was Dr. Newall-
before the Appropriations Committee on March 7, 1977. But at the
moment of discussion of final reports anticipated by the end of th~
year, when a response of 230 was given the committee, Dr~ Newell
knew all about the interim procedures that are involved in the handling
of a report; didn't he?
Dr. GRIESEMER. Yes.
Mr. Moss. I believe you were then with the agency in July of 1977.
Dr. GRIESEMER. Yes.
Mr. Moss. When the information given before this committee.
indicated that there would be 119, a reduction of 111 in the estimate.
Am I correct on that?
Dr. GRIESEMER. I don't know, but it sounds reasonable.
Mr. Moss. Well, it shouldn't only be reasonable; it should be ac-
curate,
Dr. GRIESEMER. I have no reason to believe it is not accurate; I
accept your word.
Mr. Moss. You gave us a list of the reports, and all we did was .to
tabulate it, It came out 119.
So, that was a more careful, perhaps, evaluation of the potential
for issuing of reports. But 20 is 99 short. of 119. And so we have `99
fewer reports than we were promised as of January 1.
I believe it is true that, in the context of the hearings of the Appro-
priations Committee and the hearings of this subcommittee, that our
interest was on the adequacy of the staff and resources of the Agency
to handle the reports. And when `we are told that we will get 119 and
we get 20 it does not help in trying to plan legislative recommendations.
It certainly is not helpful to the Appropriations Committee in deter-
mining as it was there that less than 10 percent of the number promised
were actually delivered.
Perhaps, if the whole story was laid on the table at the time of the
hearing, with all of the hedging about that we now hear, it might
have been possible that we wou.d have. ~ia~d more, resources made
available to handle reports.
Dr. GRIESEMER. Mr. Chairman, I am sorry if it appears there
is hedging. I am not attempting to hedge at all.
You are quite right about the 20 chemicals. I might point out,
however, that we have transmitted to regulatory agencies informa-
tion oil a great many chemicals. We have identified in the last 15
months 82 animal carcinogens. We would not have had some of the
testimony this morning and questions related to hair dyes, for example,
if we were not doing our jobs.
Mr. Moss. I have checked~ with a number of agencies as to the
relative value of the draft reports, the reports other than final
PAGENO="0039"
33
reports, in the agencies in the regulatory field, agencies under the
jurisdiction, of the subcommittee. They have taken the position without
exception that they cannot act on other than final report data. Do you
know of any instance where they have acted on other than final report
data?
Dr. GRIESEMER. No.
Mr. Moss. Then we must, for purposes of regulatory use, deter~
mine only or rely solely upon final reports. Doesn't that appear to be
reasonable?
Dr. GRIESEMER. On NOT's final reports, yes.
Mr. Moss. That's right.
And therefore; whatever the stage might be-interim, between the
draft, whatever the number of the draft, and the final report-it is of
no value to agencies for regulatory purposes.
Dr. GRIESEMER. It may serve to increase their awareness of a prob-
lem that may give them time to respond.
Mr. Moss. But they are regulators. They are not just to be aware;
they are supposed to regulate, Doctor.
Dr. GRIESEMER. In order to regulate, they have to gather rnforma-
tion related to the chemicals in question.
Mr. Moss. And therefore the value of the work of your agency to
the regulators is measured in the number of final reports made available
to them
Dr. GRIESEMER. Yes; and in their quality.
Mr Moss The Chair yields to the gentleman from Tennessee
Mr. GoRE. Thank you, Mr. Chairman.
The prepared remarks of Dr. Upton, I think, clarify a little bit the
importance of this review procedure in determining whether or not a
report is final. He said here this morning. "After review the Institute
publishes a report of the findings announced in the Federal Register
and informs the public via the media."
You have testified that as much as 90 percent of cancer may be
environmentally caused; and, the effort to attack that problem is
through these testing procedures. You told us earlier that you were
going to have 119 test results finalized, printed, reported to the public.
You have only done 20.1 think that there is hedging to the extent that
the kind of response that would be most helpful to us and to the people
that we represent is for you to say, "Yes, we failed to meet our goal.
here are the reasons .why. Here's what we propose to do to improve
the process in the future."
But, instead, you insist on focusing all this attention on, "Well,
yes, only 20 have been printed, but 80 more have been submitted in
various stages." But the public does nOt find out about any of those.
The public has not been told about the hazards in any of those sub-
stances and will not be until the review process is completed
To that extent, it is playing ~with words to say that it is a final
report when the public is not even told about it. And to say that the
scientific community is given the statistical results and pretend that
that somehow is a substitute for letting the public know that X, Y, Z
products increase the hazard that they have of getting cancer.
Thank you, Mr. Chairman.
PAGENO="0040"
34
Mr. Moss. The Chair recognizes Mr. Segal, counsellor the committee.
Mr. SEGAL. Mr. Chairman, I would like to ask permission to insert
in the record a letter that was submitted to you dated January 5, 1978
which has a two-page attachment to it entitled "National Cancer
Institute Bioassays."
Mr. Moss. The Chair is going to ask unanimous consent that such
documents as have been supplied to Members in their hearing folder
be permitted to be inserted in the record as determined necessary for
the completionof the reccrd. Is there objection?
Hearing none, such will be the order.
[The letter and attachment referred to follow:]
PAGENO="0041"
35
DEPARTMENT OF HEALTHr EDUCATION. AND WELFARE
PUCLIC HEALTH SERVICE
NATIONAL INSTITUTES OF HEALTH
CETHESDA, MARYLAND 20014
`Januar~r 5, 3.978 NATIONAL CANCER INSTITUTE
* .".
~p._ *
* em
Dear Mr. Chaii~an: .
in response to the telephone request of Mr. Elliott Seg~l.. of your staff
on December 22, 1977, I have enclosed copies of the preliminary data.
presently available on the National Cancer Institute1s `(Nd' s) bioassays
of hair dyes and telated chemicals. Added to the list of hair dye
ingredients being tested for carcinogenicity by MCI are two azo dyes,
direct black 38 and direct blue 6, which we understand are found in
some temporary rinses, and semi..pexmanent hair dye products.
Data on. seven of. the chemicals are in the form of drafts of technical
reports Clist enclosed) ~~hich are still being evaluated by MCI. Data
on six other chemicals are in the form of individual animal pathology
tables, raw data. which have not yet been verified by MCI. Data on
three chemicals are in manuscript form (resubmitted to the Journal
of Toxicology and Environmental Healt~), and data on one chemical are
in the reprint of a publiàhed paper.
my inspection of the preliminary data, the following chemicals eppear
to be carcinogenic for animals: 4..amino-~2~.nitrophenol, 2,4~'diami.noanisole
sulfate, direct black 38, direct blue 6; 2~nitro~l,4~phenylenediaxnine,
2,4-toluenediaxnine, o-anisidine, 4-chloro-l,2-pbenylenediamine, and
1,2-~phenylened.taaine. Three of the chemicals (4~~amino~.2.nitrophenol,
o~-anisidine, and 4.ch1oro~'l,2-pbenylenàdiaznine) are associated with.
bladder cancers. The possibility that chemicals not designated as
carcinogens may be carcinogenic in animals cannot be excluded until the
analyses are completed. .
The Honorable John H. Moss
* . Chairman, Subcommittee on
OversLght and Investigation
Committee on Interstate and
* * Foreign Commerce
House of Representatives
Washington, D.C. 20515
PAGENO="0042"
36
* Page 2 - The Honorable John H. l4oss
~ll of the draft technical reports and the data in the individual animal
~o~ogy tab]ás Cwhich will be incorporated into, the technical reports)
are presently being.reviewed by NCZ to insure scientific accur4cy. lqb.en
verified and con~letëd, the technical reports will be reviewed by the
Carcinpgenesis Testing Program's advisqry committee (the clearinghouse
on Environiental Carcinogens), published, ~nd' announced in the Pederal
Register. * .* . .
As additional information becomes available, ye. ebail be.ha~py to ~keep
you informed. * *
* . Sincerely,
-4'..
* Richard A. Griesemer, .p.V.Z4., Ph.D.
* Associate Director for.
Carcinogenesis Testing Program
* Division of Cancer Cause and Prevention.
15. Enclosures
PAGENO="0043"
- (Synonymn
* HAIR
4_ami2~ni~ro5theno1*
(o-nitro-p-aminophenol)
2,4-diaminoanisole sulfate
* (4-methoxy-m-phenylenediamine)
direct black 38
direct blue 6
2-nitro-l,4-phenylenediamine
(2-nitrà-'p-phenylenediamine)
2,4-toluenediamine
(m-toluenediamine)
4-nitro-l,2-phenylenediasine
* (4-nitro-o-phenylenediamine)
l-phenyl-3-methyl-5-pyrazolone
(3-methyl-l-phenyl-5-pyrazolone)
N-pbenyi-l,4-phenylenediamine
(N-phenyl-p-phenylenediamine)
l.,3-phenylenediamine
(m-phenylenediamine)
l,4_phenylenediamine*
(p-phenylenediamine)
resorcinol**
2, 5-toluenediaifline
(p~to1uenediamine)
NCI BIORESAYS
Preliminary Results
DYE INGREDIENTS
carcinogenic
carcinogenic
carcinogenic
carcinogenic
carcinogenic
carcinogenic
CAS Number'
00119-34-6
00615-05-4
00072-57-1
02602-46-2
05307-14-2
0005-80-7
00099-56-9
00089-25-8
02198-59-6
00541-69-5
00624-18-0
00108-46-3
06369-59-1
Available Data
Individual Animal Pathology Table
* Draft Technical Report
Draft Technical Report
Draft Technical Report
Individual Animal Pathology Table
Submitted to 3. Toxicol. Environ.
Health
Individual Animal Pathology Table
Individual Animal Pathology Table
Draft Technical Report
Submitted to J.Toxicol. Environ.
Health
Individual Animal Pathology Table
Published in Toxiáol. A~pl.
Pharmacql. 1974
Draft Technical Report
PAGENO="0044"
*9km tests for carcinogenicity negative.
**Skin tests for carcinogenicity negative; no other tests in progress.
Available Data
Individual Animal Pathology Table
Draft Technical Report
Submitted to.7. Toxicol. Environ.
Health
Draft Technical Report
Nd BIOASSAYS - Page 2
Chemical
CR5 Number . (Synonymn) * Preliminary Results
RELATED. CHEMICALS
00134-29-2 o-anisidine carcinogenic
(2-methoxyaniline)
00095-83-0 * 4-chloro-l,2-phenylenediamine carcinogenic
(4-chloro-o-phenylenediaaine)
00615-28-1 1-2-phenylenediamine carcinogenic
(o-phenylenediamine)
20265-97-8 p-anisidine
(4-methoxyaniline)
PAGENO="0045"
39
Mr. SEGAL. I would just like to pursue the point raised by the
chairman on when actions are taken and the public is aware of interim
reports versus final reports. I would like Dr. Upton to address this
question: On Sunday, December 25, 1977, on the program issues
and answers, you were quoted as advising consumers not to use pro-
ducts that contain 2,4 diaminoanisole and indicated, "I wouldn't
want to use hair dyes on my hair knowing what I know about the
possible risks."
Looking at the letter of January 5, 1978, there are three additional
compounds listed that are indicated as potentially causing bladder
cancer. The first on the list is 4-amino-2-nitrophenol. And under the
submission to us, it says "preliminary results, carcinogenic."
On the second page, there is an o-anisidine, which is listed as
carcinogenic, and a 4-chloro-ortho-phenylenediamine which is also
listed as carcinogenic.
Would you, Dr.. Upton, make this same statement about these three
compounds as you made about 2,4 DAA?
Dr. UPTON. Mr. Segal, I have not reviewed those data on the other
two. So, I would not be .pre~ared at the moment to comment on them.
Mr. SEGAL. Would you, Dr. Griesemer?
Dr. GRIESEMER. I can add to the record that we have completed-
first of all, that we are testing 13 hair dye product ingredients for
carcinogenicity in animals. One of those, resorcinol, has been tested
only by skin painting and was found not to be carcinogenic under
those conditions and need not concern us more.
On the other 12, we have completed in-house studies on five of them.
Four are carcinogenic in animals, according to ou~ interpretation.
Two others-
Mr. SEGAL. Can you identify the four. The list that was submitted
to us contains more than four.
Dr. GRIFISEMER. Yes. 4-amino-2-nitrophenol, 2,4-diaminoanisole
sulfate, direct black 38, direct blue 6, 2~nitro-1,4-phenylenediamine,
and 2,4-toluenediamine are six chemicals that. we have tested that we
belie've are carcinogenic for animals.
On four of those the studies are completed. The other two are not yet
completed, but the evidence is almOst certainly that they are
carcinogenic.
Mr. SEGAL. Does that mean that the ones on page two-the two
methoxy compounds, the 4-chloro, are not yet complete?
Dr. GRIE5EMER. Yes. On page two, there are four chemicals that we
understand are not ingredient~ in hair dyes. So, I did not address that
issue. One of them is completed, the 1,2-phenylenecliamine is an animal
carcinogen according to our interpretation. And two others have
sufficient information again to make it almost certain that they are
animal carcinogens: those are the ortho~anisidine and 4-chloro.-1 ,2-
phenylenediamine.
Again, the latter three are thought not .to be in hair dyes but are
mtermediates in hair dye production.
Mr. SEGAL. Sticking with the six that you, indicated were cancer-
causing agents listed on the first page of the report, has all of this
information on these chemicals been transmitted to the regulatory
agencies, for example, FDA?
PAGENO="0046"
40
Dr. GRIESEMER. The package that was submitted as a status porret
to this subcommittee has also been transmitted to Commissioner
Kennedy of the FDA.
M?. SEGAL. Was that an unusual procedure because we had asked
for it? Or do you do that routinely?
Dr. GRIESEMER. No; that was an unusual procedure.
Mr. SEGAL. It was unusual.
Dr. GRIESEMER. Yes.
Mr. SEGAL. Of the ones that are listed as draft technical report,
are you suggesting to FDA that they take regulatory action based on
the draft report?
Dr. GRIESEMER. No.
Mr~ SEGAL. What would you suggest to them?
Dr. GRIESEMER. That they wait for the final verified report.
Mr. SEGAL. And these final verified reports are the same reports
that-Wall three of them, if you look at the chart [see p. 9]-had been
promised by the end of this year. Is that not cOrrect?
Dr. GRIESEMER. Two of them are experiments that were just begun
this year and were completed in 90 days. That is the direct black 38
and the direct blue 6-
Mr. SEGAL. Excluding the colors.
Dr. GRIESEMER. The others are part of that group of chemicals.
Mr. SEGAL. So, the other four, excluding the two pertaining to
colors, only one has been in a final report submitted to FDA; and the
other three are in some form of draft. Is that right?
Dr. GRIESEMER. One of them has been-yes, that is correct:
Mr. SEGAL. The final report, the 2,4 DAA has not yet been printed
in the Federal Register:
Dr. GRIESEMER. That is correct.
Mr. SEGAL. So, of all of the chemicals, the six known cancer-causing
agents, none of them have come out in the final report form; is that
right?
Dr. GRIESEMER. That is correct.
Mr. SEGAL. Thank you, Mr. Chairman.
Mr. Moss. Mr. Maguire?
Mr. MAGUIRE. Thank you, Mr. Chairman.
In responding to Mr. Waxman's questions earlier, Dr. Upton-and
I gather you said the same thing on television in December-you
indicated that it would be prudent for those who dye their hair not
to use these particular hair dyes. Now, that leads to the question of
whether or not, given the scientific information which we now have,
those ingredients should be removed from the hair dye products.
Would you agree that they should be?
Dr. UPTON. Mr. Maguire, I think that question is a difficult one.
The data do not enable a confident assessment of risk to human popu-
lations. I would certainly favor labeling of the package in a way ~that
informs the consumer of the presumption of risk.
I am not a regulator. My experience is. in the field of research. I
would not feel confident going so far today as to say that those ma-
terials should be banned from hair dye preparations. I think that one
of the issues inevitably is whether there are acceptable alternatives.
If there are none, should the consumer have the option to determine
for himself or herself. We permit the sale of cigarettes. To my mind
PAGENO="0047"
41
the evidence linking cigarette consumption to cancer in humans is
overwhelming. But the consumer has the right to determine whether
or not to smoke.
I would not choose to use the hair dyes that contain these com-
pounds. To deny others that opportunity, given the lack of evidence
we have in the human, seems tome perhaps to go too far at this point
in time.
Mr. MAGUIRE. Under the law, Dr. Upton-I am referring to the
Food, Drug, and Cosmetic Act-there is a section OO1A, which is
very curious. It reads, "A cosmetic shall be deemed to be adulterated
if it bears or contajns any poisonous or deleterious substance which
may render it injurious to users under the conditions of use prescribed
in the labeling thereof or under such conditions of use as are customary
.or usual."
Then it goes on: `Provided that this provision shall not apply to
coal tar hair dye."
That is the only exception in this paragraph I have done a little
research on it. Apparently Congress is at fault in this case for having
acceded to a request from lobbyists representing the hair dye industry
at that time for the inclusion of this exception.
Would you feel that there was merit in having this exception in the
law? Or would you recommend to the Congress that that exception
be eliminated-whatever may be the answer to my earlier question.
Dr UPTON Again, Mr Maguire, I confess that ~[ am not closely
enough involved with the regulatory process to feel confident of my
judgment. I think these are societal issues. They are issues that obvi-
ously fall to your purview.
I do not equate a hair dye preparation with food on the grocery
store shelves.
Mr. MAOUIRE. All right; but that is not really the issue. The issue
is whether, in your judgment, there is any basis for making a special
category of all of the cosmetics that we might be dealing with for
coal tar hair dyes in the law. In other words, every other cosmetic is
subject to this test of safety. Coal tar~hair dyes have been specifically
excluded by the Congress, not from particular findings with respect
to whether they cause cancer or not, but from the very process itself
of making a determination. Is there any possible justification for that
in your judgment?
Dr. lIPTON. I know of no scientific justification.
Mr. MAGUIRE. I thank you.
Mr Chairman, it is my intention to introduce legislation to elimi-
nate this extremely unwise and unmerited special provision in the law
for coal tar hair dyes. I think they should be subject to the same
process and the same testing procedures and the same test of judg-
ment that apply to each and every other cosmetic under the law.
That does not prejudge the issue with respect to the scientific
findings. That simply says that they should be dealt with as every
other cosmetic is dealt with. I do be1ieve~ given the scientific data
that ~we have, that it is enormously important that we plug that
loophole if we are going to protect American citizens.
Thank you, Mr. Chairman.
Mr. Moss. The Chair recognizes the gentleman from Pennsylvania,
Mr. Marks.
PAGENO="0048"
42
Mr. MARKS. Thank you, Mr. Chairman.
We were talking a moment ago about perhaps there ought to be a
consumer's choice to determine what one should do or not do. That
leads us to testing. That leads us to credibility.
What can we believe? I remember the go-around on saccharin
where it appeared as if-at one point at least the public was told
that one would have to ingest 850 cans of a certain type of liquid a
day for many years before one could approach the type of tests that
were made to come up with the results.
In the case of hair dyes, why would you use animal feeding studies
where hair dyes were ingested in them? Should not chemicals be
tested in a manner consistent with their use? Then, when it finally
comes out, people can at least have some faith and understanding
based on the tests that were used.
Dr. UPTON. I think, wherever it is feasible to do so, studies ought
to use routes of administration more nearly comparable to the routes
of administration that are associated with use in practice. The bio-
assay experiments were intended as screening procedures. They were
set up in a way that permitted a large number of compounds to be
tested under standard conditions and to insure that many tissues of
the body did, in fact, come into contact with the agent in question.
I do not think that one can argue that this. particular bioassay
experiment was designed specifically to look at the hazards associated
with use of compounds as hair dyes. The fact of the matter is, however,
that, Qnce in the body, the agents travel to various organs and, as
we see, produce tumors in the thyroid, in the skin, in the glands of
the skin; so that, even though the dye substances were taken in the
body by mouth, carcinogenic effects on the skin resulted.
Mr. MARKS. Did you perform a topical treatment test with hair
dyes, Doctor? If so, what were your results?
Dr. UPTON. I am not aware that these have been done in the bio-
assay program. Perhaps Dr. Griesemer has other information.
Dr. GR~ESEMER. Yes; there were three skin painting studies which
did not reveal carcinogenicity under those conditions.
Mr. MARKS. Did or did not?
Dr. GRIESEMER. Three chemicals.
Mr. MARKS. That did not?
Dr. GRIESEMER. Did not.
Mr. MARKS. Thank you.
Mr. MAGUIRE. Will the gentleman yield?
Mr. MARKS. Yes.
Mr. MAGU1RE. Is it your understanding scientifically that those
studies did not show cancer causation because the material was not
absorbed through the, skin? Or, alternatively, if it was absorbed
through the skin, that, once it got inside the body, it did not travel
and become a carcinogen?
Dr. ~RIES~MER. I believe the reason some of the experiments that
have been published-and perhaps one of ours-did not reveal cancer
is that the doses that can enter the body through the skin are limited.
Using small numbers of animals, if one wants to demonstrate that a
chemical has the capacity to produce cancer, one has to use large
amounts and reach all the parts of the body.
PAGENO="0049"
43
Mr. MAGtTIRE. Would you then say that it `is not possible to say
on the basis of skin painting studies alone that the product or the
substance is safe?
Dr. GRTES~MEE. Skin painting is a good first experiment, but by
itself is not enough.
Mr. MAGUIRE. What would be your comment then on the public
statements bythe Cosmetic, Toiletry, and Fragrance Association that
their studies-which were of this sort-prove that the coal tar hair
dyes are in fact safe?
Dr. GRTESEMER~ We have demo~istrated that some of the chemicals
are animal carcinogens. We believe a. wider analysis is needed to de-
termine whether or not they pose a risk to man.
Dr. UPTON. Might I comment on that point, too, Mr. Chairman?
Mr. Moss. Indeed.
Dr. UPTON. I think' one of the serious limitations in the animal
studies that we are looking at and discussing is the relatively small
numbers used. If one uses 50 animals in the dose group. then one
would miss a 1 percent carcinogenic effect; there aren't enough animals
to demonstrate it. `But clei~rly a 1-percent effect in a population of
200 million people would be 2 million victims.
Mr. MAGUIRE. Excuse me, Doctor; are you talking about the skin
painting studies or the feeding studies?
Dr. UPTON. In either case, if the numbers of animals are small,
one has to have a large effect to detect it. If, in the painting experiment,
the doses that were delivered are small, the number of animals are
small, one might have to greatly increase the numbers of animals to
`see a small effect, an effect which, in the human population, would
still be too large to be accep~table.
Mr. MAoimun. The CTFA has also criticized your studies. In
addition to having critics criticize their studies, they have criticized
your studies on the ground that the doses were massive and that they
were feeding studies, which is not the condition under which the dyes
are used by human beings.
I `think you have given partial responses to that kind of criticism
in your earlier answer. But would you like to summarize as to why
you do or do not feel that those criticisms are valid?
`Dr. GRIESEMER. I think it is important to recognize that a series
of experiments are required to evaluate the risks from chemicals.
The test for carcinogenicity alone, because of its objective, requires
that very large doses be used and as many animals as is economically
feasible, by whatever route will' permit the chemical to enter the body.
If then one finds no cancers,~ one ha~s some confidence in not studying
that chemical any further but doing additional experiments on those
that `do pose a problem.
Mr. MAGUIRE. I `thank the gentlemen from' Pennsylvania for
yielding. `
Mr. Moss. Does the gentleman from Pennsylvania have any further
questions?
Mr. MARKS. Nothing more, Mr. Chairman; thank you.
Mr. Moss. Does the gentleman from. Tennessee desire recognition?
Mr. GORE. Yes, Mr. chairman.
Mr. Moss. The gentleman is. recognized.
24-600 0 . 78 - 4
PAGENO="0050"
44
Mr. GoRE. Dr. Upton, on page 6 of your testimony you describe
briefly the process that you go through to select, chemicals to be
tested. In light of the fact that your resources are so limited, in light
of the fact that there are 4.5 million chemicals in our environment and
you have the ability, you say, to test only as many as 100 each year,
how could a university professor, for example, who determines through
his or her own work that a particular substance is carcinogenic plug
into your process? Can they make recommendations to the review
board, the chemical selection subgroup?
Dr. UPTON.. Yes, indeed. The meetings of that group can receive
information from any and all sources. We fund a substantial volume
of grant-supported activity in this area. So, in addition to the work
in the bioassay program, which is done largely on contract, a great
many experiments are done through the grant mechanism.
I think the Institute is anxious to receive any and all indications
of potential carcinogenicity so that it can explore where needed.
Mr. GORE. Are you aware of any kind of pressure from particular
industry groups not to test particular substances?
Dr. UPTON. I have been unaware of such pressure. Dr. Griesemer?
Dr~ GRIESEMER. I have not received any either.
Mr.. GORE. That's good.
I have some difficulty in getting a clear view of what this Nation's
response ought to be to environmental causes of cancer. One way to
look at it is to say that if we have got 4.5 million chemicals and 90
percent of cancer may be caused by artificial substances put into the
environment, then we are not really going to cure or prevent cancer
unless we dramatically escalate this Nation's effort to seek out those
among. the 4.5 million chemicals that clearly are carcinogenic, inform
the public about it, and escalate our efforts to protect the public from
those substances.
If we got 4.5 million and we are doing 100 a year, am I wrong in
concluding that this is just a pitiful response by this country to the
threat that we are facing?
Dr. UPTON. Mr. Gore, I think it is an inadequate response. I think
we must increase the effort. I despair of being able within our life-
times to do enough animal testing to deal with the thousands of com-
pounds that are there. I think we badly need more effective short-
term tests. Reference was made to the Ames test and the fact that
it is not 100 percent predictive of responses in animals.
We need to understand better what the exceptions are, why it
does not predict more effectively. There are classes of carcinogens
that are negative in the' Ames test now-the so-called promoting
agents.
I think that through a combination of approaches epidemiological
studies of the human population itself, such as Dr. Fraumeni described
to us, looking for high-risk groups, trying to determine the causative
factors underlying changes to high risk and also improving our knowl-
edge of the cancer process so that we can devise more effective test
methods and experimental systems-all of these have to be made.
Our effort will be to develop over a broad front more vigorous and
more effective approach to this problem.
Mr. GORE. Yes; but you cannot do it unless you get the money
from the Congress. And we cannot do it unless there is the support
PAGENO="0051"
45
from the people. And the people are not going to be willing to do it
until they really understand the magnitude Of this threat.
It is the second leading cause of death in the country. In terms of
the heartache and so forth, it is right up there.
Mr. Waxman was talking earlier about the general public reaction
to environmental causes of cancer. Maybe we need to develop a
language that the scientific community can use to' communicate with
the public to have a regulate update of what substances-three
columns: What substances cause cancer in our view; second column,
what products they appear in; third column, w~hat is the percentage
risk relative to other causes of cancer that we are aware of.
We could really publicize that information and let the public know
what this threat is so `that they can put pressure on their elected
representatives to face up to this challenge. I am in favor of doing it.
I think we ought to dramatically escalate our efforts to cure and pre-
vent cancer. But it is tough to get the additional money that we
really desperately need to formulate a responsive policy in this area.
The public is not made aware of what the threat is.
Mr. MARKS Would the gentleman yield?
Mr. GORE. Yes.
Mr. MARKS. May I mention that also in that we would need the
necessity of setting forth the testing procedures that were used so
that people would have the credibility of being able to believe these
things that you are now suggesting. That would be a' very important
part of that program.
Mr. GORE. Thank you, Mr. Chairman.
Mr. Moss. The gentleman from California, Mr. Waxman, is
recognized.
Mr. WAXMAN. Thank you, Mr. Chairman.
Dr. Griesemer, it is my understanding that chemicals are placed
on the bioassay list each year because there is some suspicion that
there is a relationship between the chemical and it's possibility of
being a mutagen. Is that a proper understanding?
Dr. GRIESEMER. If we know that the chemical is mutagenic, it tips
the scales a little stronger toward testing rather than not testing that
chemical. But the major criteria are human exposure and other evi-
dences of biologic effects in animals or man.
Mr. WAXMAN. Biological effects?
* Dr. GRIESEMER. Yes; toxicity or perhaps an incomplete study on
carcinogenicity as well as mutagenicity and teratology and all the
rest.
* Mr. WAXMAN. So, you may not have any evidence of a chemical
being a mutagen, you may not have any evidence of an adverse
effeôt, but would you then select a chemical substance solely because
as its widespread use'in the environment?
Dr. GRIESEMER. There are a few chemicals that have been selected
solely because, there is tremendous human exposure.
Mr. WAXMAN. I was interested to note that on the list I have before
me of chemicals tentatively selected for testing by NCI is ascorbic
acid; popularly known as vitamin' C. There have been those who have
suggested that this is a natural substance that may have a beneficial
effect in treating cancer as well as many other diseases.
What is the rationale for including vitamin C on the bioassay
list?
PAGENO="0052"
46
Dr. GRIESEMER. Again, it was selected primarily because of large
human exposure to rather large doses. You are quite correct; in some
experimental situations, vitamin C appears to have an anticarcino-
genic effect-which may make the design of the experiment a little
more difficult.
Mr. WAXMAN. Was there any other reason other than its prevalent
use in the environment, that it was selected?
Dr. GRIESEMER. I am sure there were other reasons; but, without
reviewing all the information in the record, I do not know.
Mr. WAXMAN. Perhaps we can get that information.
Dr. GRIESEMER. We are attempting to test some endogenous chemi-
cals, or chemicals that are essential for life.
Mr. WAxMAN. Could you explain to me "endogenous"?
Dr. GRIESEMER. Those that may be taken in excessive amounts
under some conditions.
Mr. WAxMAN. I notice that castor `oil is also scheduled for bioassay
testing.
Dr. GRIESEMER. Yes. There are some natural products that are
being tested. You may know that there are some very potent carcino-
gens .that occur naturally such as aflatoxin in the mold.
So, part of our program is a systematic approach to exploring areas
of possible carcinogenicity such as natural products or endogenous
substances.
Mr. WAXMAN. Thank you very much.
Thank you, Mr. Chairman.
Mr. Moss. The chair recognizes the gentleman from New Jersey,
Mr. Rinaldo.
Mr. RINALDO. Thank you very much, Mr. Chairman.
I am still very much interested in the budget that you have. I was
taking a look at it earlier. As we agree, it is $872 million. Twenty
percent. of that budget is used for testing on environmental causes of
cancer.~Only 1.4 percent is spent for the development of new tests.
What in your opinion is the most important part of that budget,
and how are you spending the money?
Dr. UPTON. I am not sure which part you are asking about.
Mr. RINALDO. I do not want to go through the. entire budget. I was
just giving you two instances of how it is broken down percentage-
wise.
Dr. UPTON. You asked which part of the budget is most important;
the whole budget or the carcinogenesis?
Mr. RINALDO. To what area do you assign top priority?
Dr. UPTON. At the present time, the environmental carcinogenesis
area, in my view, deserves top priority: What can we be doing to in-
crease the effectiveness of cancer prevention?
Mr. RINALDO. You said that it deserves top priority.
Dr. UPTON. Yes
Mr. RINALDO. Is it now getting top priority?
Dr. UPTON. It is getting top priority in our planning and our pro-
jections for the future.
* Mr. RINALDO. Does the National Cancer Institute conduct any
tests itself?
Dr. UPTON. Within our own facilities?
Mr. RINALDO. Yes.
PAGENO="0053"
47
Dr. UPToN. I am not certain that we do conduct any bioassay
tests within our own facilities. Our own animal space is extremely
limited.
Mr. RINALDO. Do you contract out all the tests?
Dr. UPTON. To my knowledge, all the bioassay testing is done on
contract outside the Institute's own animal space principally because
we have no adequate animal space on the campus.
Mr. RINALDO. How do you select the firm or individuals who are
awarded the contracts?
Dr. UPTON. The selection of contractors was undertaken before
my arrival. I would like to ask Dr. Griesemer if he can speak to that.
Dr. GRIESEMER. It is a competitive process with presite visits and a
continuing review of all the facilities that might be available in the
country. All of them are notified when contracts are being considered.
So, it is the ordinary competitive process that one goes through for
any contract.
Mr. RINALDO. Does NOT specifically select-
Dr. GRIESEMER. Yes.
Mr. RINALDO. You do?
Dr. GErE5EMER. We make the selection.
Mr. RINALDO. It was my understanding you went through a firm
who-
Dr. GRIE5EMER. We have support from a client contractor, Tracor-
Jitco, who assist us in evaluating laboratories and in visiting labora-
tories. But we make the decisions.
Mr. RINALDO. They assist you. I assume they receive a management
fee for this assistance?
Dr. GRIESEMER. Yes.
Mr. RiNALDO. What is the amount of fee that they receive?
Dr. GRIESEMER. I cannot answer the question~ It is a total con-
tract fee, and I do not know th~ amount. It is: somewhere in the
vicinity-their total costs are somewhere in the vicinity of 15 percent
of those contracts with which they deal. But their award fee is much
smaller than that. I am sorry. I do not know the amount. We can
provide that for the record.
Mr. RINALDO. Mr. Chairman, I would like to have that.
Mr. Moss. Without objection, the record will be held at this point
to rece~ve the material.
[The following information was received for the record:]
PAGENO="0054"
48
Award Fee Arrangement--TracorJitco -
Tracor Jitco Contract No. NO1CP 43350 provides for an award fee except
for the first year of the contract which included a base fixed fee
and an award fee. An amount for the award fee pool is established
from which award fee amounts are determined by evaluations of the
contractor's performance by an NCI Performance Evaluation Board.
Fee amounts established by the contract and reimburseable costs are
as fOllows:
Cost $38,011,930
Base Fixed Fee 77,729
Available Award Fee 3,208,554
Pool
Fee amounts awarded to date compared to amounts available to date:
Performance Period Amount Awarded Award Fee Available
3/1/74-6/30/74 $21,980 $27,138
7/1/74-10/31/74 23,067 27,138
11/1/74-2/28/75 23,339 27,138
3/1/75-5/31/75 22,523 27,138
~6/l/75-9/30/75 161,458 258,333
10/1/75-1/31/76 151,125 258,333
2/1/76-5/31/76 159,650 258,333
6/1/76-9/30/76 125,292 258,333
10/1/76-1/31/77 90,933 258,333
2/1/77-5/31/77 102,042 258,333
6/1/77-10/31/77 145,958 258,333
PAGENO="0055"
49
Mr. RINALDO. Would you say that this is the most efficient manner
in which NCI can1 operate? Or do you think that you could operate.
more efficiently and get more value, more testing, more data per
dollar spent?
Dr. GRIESEMER. Yes, that contract runs through May of 1979.
We are in the process of reviewing our whole management of the
operation. There are other options which we are considering. It has
been, in the last 1~ years a very cost effective operation.
Mr. RINALDO. In other words, are you stating that there is a good
possibility that, when the contract runs out in May of 1979, there will
be a neW method?
Dr. GRIESEMER. It is possible.
Mr. RINALDO. I have no further questions, Mr. Chairmam.
Mr. Moss. Are there further questions?
If not, the witnesses will be excused with the thanks of the com-
mittee. The committee will stand in recess until 2 o'clock, when we
will again convene in this hearing room.
[Whereupon, at 12:30 ~ the subcommittee stood in recess.]
AFTER RECESS
[The subcommittee reconvened at 2 p.m., Hon. John E. Moss,
presiding.]
Mr. Moss. The subcommittee will be in order.
At this time I would like to invite Edward J. Baier, Deputy Direc-
tor, National Institute for Occupational Safety and Health.
He is accompanied by Dr. Norbert Page, Chief, Priorities and Re-
search Analysis Branch, Division of Criteria Documentation and
Standards Development.
Gentlemen, would you be sworn?
Do you solemnly swear that the testimony you are about to give
this subcommittee shall be the truth, the whole truth, and nothing
but the truth?
Mr. BAlER. I do.
Dr. PAGE~ I do.
Mr Moss Would you identify yourselves for the record?
Mr. BAlER. I am Ed Baier.
Dr. PAGE. I am Dr. Page.
Mr. BAlER. Mr. Chairman, would you prefer that I read my state-
ment, or would you prefer that I highlight it?
Mr Moss Mr Baier, whichever way you feel most effectively
assists you in telling us what you want to tell us will be fine
Mr. BAlER. Then I will go through the statement.
Mr. Moss. Very well. . S
Please proceed.
PAGENO="0056"
50
TESTXMONY OF EDWARD J. BAlER, DEPUTY DIRECTOR, NATIONAL
INSTITUTE POR OCCUPATIONAL SAFETY AND HEALTH, CENTER
FOR DISEASE CONTROL, DEPARTMENT OF HEALTH, EDUCATION,
AND WELFARE, ACCOMPANIED BY NOREEItT P. PAGE, D.V.M.,
CHIEF, PRIORITIES AND RESEARCH ANALYSIS BRANCH, DIVI-
SION OF CRITERIA DOCUMENTATION AND STANDARDS DEVEL-
OPMENT
Mr. BAlER. Mr. Chairman, and members of the subcommittee, I
am Edward J. Baier, Deputy Director of the National Institute for
Occupational Safety and Health-NIOSH. Accompanying me toda
is Dr. Norbert P. Page, Chief of the NIOSH Priorities and Researc
Analysis Branch. We are pleased to appear before you today to discuss
the role of NIOSH in investigating certain chemical causes of cancer.
You asked us to discuss two specific chemicals: ethylene dichloride,
an intermediate in the production of other chemicals, including vinyl
chloride, and 2,4-diaminoanisole, which is used in certain hair and
fur dye formulations.
Under the Occupational Safety and Health Act, NIOSH is. respon-
sible for conducting occupational safety and health research, recom-
mending standards to the Occupational Safety and Health Adminis-
tration (OSHA) and providing technical assistance in evaluating
employee exposures. NIOSH and OSHA share manpower development
and training responsibilities.
In developing criteria for recommended standards, we attempt to
evaluate all available data relevant to establishing an occupational
standard and place particular importance on data indicating animal
or human carcinogenicity and other chronic health effects.,
When we receive new information on the carcinogenicity of a chem-
ical substance or physical agent, we may issue a Current Intelligence
Bulletin, providing background information on the chemical, includ-
ing its known toxicity to man and animals, known producers and
users, estimated extent of occupational exposure, and precautions
which can be taken to reduce the hazard.
These bulletins are now distributed to over 5,000 members of the
occupational safety and health community, Government agencies,
management, labor, public interest groups, a~d others. As a result of
the evaluation of new data, we decide what further action may be
necessary. This may include developing new or revised criteria docu-
rnents for transmittal to OSHA and conducting additional epidemio-
logic or laboratory research to better characterize the hazard.
ETHYLENE `DICHLORIDE
In 1972, the Institute developed a priority list of chemical and
physical agents based on the number of workers exposed and the
known toxicity of the agents. Relatively high on that list were a num-
ber of chlorinated hydrocarbon solvents, including ethylene dichioride.
Approximately 10 billion pounds of ethylene dichloride are con-
sumed each year in the United States by a variety of industries. Most
of it is used as an intermediate in the production of other chemicals,
including vinyl chloride, 1,1 ,1-trichloroethane, trichloroethylene,
perchloroethylene, vinylidene chloride, and ethyleneamines.
PAGENO="0057"
51
Occupational exposure to ethylene dichloride in those processes is
minimal. A total of 2 million workers may receive some exposure to
ethylene dichioride, with perhaps 200,000 receiving a substantial
exposure primarily during its use as a solver t in textile cleaning and
metal degreasing, in certain adhesives, and as a component in fumi-
gants. Low level exposure of ~as station attendants can also occur
from its use as a gasoline additive.
In March of 1976, NIOSH transmitted a criteria document to the
Department of Labor recommending a tenfold reduction' in the existing
Federal standard for ethylene dichloride from 50 to 5 parts per million
parts of air-ppm. This recommendation was based on reports of
adverse effects on the nervous system and liver of workers exposed to
10-15 ppm ethylene dichloride. Exposure at higher levels was also
reported to affect the cardiac and respiratory systems. We further
advised nursing mothers not to work with ethylene dichloride since
the chemical has been found in the milk of exposed mothers. In addi-
tion to an environmental limit, NIOSH made recommendations for
medical examinations, labeling and posting requirements~ personal
protective equipment and clothing, informing employees of hazards,
work practices, and moRitoring and recordkeeping procedures.
When the criteria document was transmitted to OSHA in March
1976, there were no reports that ethylene dichloride caused cancer in
animals or man. We did note that information on this subject was
inadequate and that the National Cancer Institute (NCI) was con-
ducting bioassay tests on the chemical.
In December of 1977, NCI reported preliminary results from those
tests indicating that male and female rats and mice fed ethylene
dichiOride for 78 weeks had significant excesses of site-specific malig-
nant and nonmalignant tumors.
NIOSH is currently analyzing these preliminary results and is
awaiting NCI's final report. The Institute is also preparing a Current
Intelligence Bulletin which will advise the occupational health com-~
munity as to the potential significance of those preliminary NCI data.
If the final results of the NCI study on ethylene dichloride establish
it to be carcinogenic, the Institute will transmit revised recommenda-
tions to the Occupational Safety and Health Administration. Addi-
tional recommendations will also be made for appropriate medical
monitoring, respiratory protection, engineering controls, and work
practices.
2,4-DIAMINOANISOL~
This past fall, NIOSH learned' that a preliminary analysis of
National Cancer Institute data indicated that laboratory rats and
mice fed 2,4-diaminoanisole sulhite experienced a significant excess
of site specific malignant tumors as compared with controls. On
January 13, NIOSH issued a. Current Intelligence Bulletin recom-
mending that 2,4-diaminoanisole--.also known as 4-methoxy-m-
pheylenediamine-and . its salts be handled in the workplace as if
they were human carcinogens. .
Approximately three out of four current oxidation or permanent~
hair dye formulations. contain 2,4-diaminoanisole or its sulfate salt, ac-
counting for about $200 million in annual retail sales. Although NIOSH
is unaware of any current domestic production of 2,4-diaminoanisole,
PAGENO="0058"
52
approximately 25,000 pounds a year are imported. NIOSH estimates
that about 400,000 workers have potential occupational exposure,
primarily hairdressers and cosmetologists. A relatively small number
of fur dyers are also exposed to the chemical.
NIOSH has conducted two epidemiologic studies that suggest
excess cancer among cosmetologists. One study indicates an excess
of genital cancer among hairdressers and cosmetologists. The other,
which has not yet been completed, suggests excess cancer of a number
of organ systems among this occupational group. It should be rec-
ognized that hairdressers and cosmetologists are also exposed to a
wide variety of other chemicals and that the epidemiologic studies do
not clearly demonstrate a casual connection between hair dyes and
cancer. Nevertheless, we believe that the studies give additional cause
for concern.
NIOSH has also been informed that unpublished data recently
acquired by the Food and Drug Administration [FDA] indicate that
2,4-diaminoanisole penetrates the skin and enters the system of both
man and the rhesus monkey. There are other rpports indicating that
2,4-diaminoanisole is mutagenic in bacterial systems and in the fruit-
fly-Drosophila. These reports are of interest because correlations
have been suggested between mutagenicity in bacterial systems and
carcinogenic potential in higher systems.
As an interim and prudent measure, pending further evaluation of
the carcinogenicity of 2,4-diaminoanisole, NIOSH recommends that
occupational exposure to 2,4-diaminoanisole and its salts be minimized
by engineering and workpractice controls. In particular, skin exposure
should be avoided.
Although substitution is a possible control measure, NIOSH rec-
ommends that caution be exercised in selecting substitutes for dye
formulations and other products containing 2,4-diaminoanisole. Al-
ternatives should be fully evaluated for possible human health effects.
This is particularly important in view of the many questions that
have been raised recently regarding the safety Of numerous components
of hair dye formulations.
These two examples illustrate some of the kinds and sources of data
that contribute to our evaluation of carcinogenicity. As shown in the
accompanying table, we receive information on carcinogenicity from a
variety~ of sources, including the National Cancer Institute bioassay
program, the published scientific literature, industry studies, and
NIOS}L~sponsored studies.
Such hazards may be identified by epidemiologic studies of people
who ha~e been exposed to suspect chemical agents as..welias by animal
experiments. After reviewing all available information, including
biological effects and exposure conditions, NIOSH determines the need
for recommended occupational standards and specific preventive
measures, as well as further research to better assess the potential
hazards.
Mr. Chairman, this concludes my prepared testimony. Dr. Page and
I will be happy to answer any questions you or members of your sub-
committee may have.
Mr. Moss. Without objection, the table attached to your statement
will be included in the record at this point.
[The table referred to follows:]
PAGENO="0059"
OCCUPATIONAL CARCINOGENS*
Substance source of Data
Industry conducted/
Published scientific sponsored studies NCI bioassay NIOSH
literature (unpublished) data data
~17ltnuie x
~ X
X X
1Benzene X X
..Benzid~ine I
~Berylliu~ X
~!~Beta-Napbthyla.ine X
~1i$eta-Propiolactone X
H~Bis.-Chloromethyl Ether X
U~arbon Tetrachloride X X
fflfchlorofo~ X I
:UJ~0m11~M (VI) X. X
-certain coimpounds- -
~~oal Tar Products X
-coal tar, coal tar pitch
creosote-
4oheO~~~ Ealisions X X
z:~Pioxane X X
;wII~thyleneimine X
.t~DKeP0fle X X
1~f$ethyl ~hloro.ethyl Ether X
~$-NitrosodIaeLhylaaine X
Nickel, Inorganic X X
x x x
~!~inyl chloride x x
llh:et7lenin0tIn0t~1~ X
H1~3,3-Dichlorobenzidine (and X
its salts)
*NI0SH Recoendations
PAGENO="0060"
OCCUPATIONAL CARCINOGENS* Page 2
Substance Source of Data
Industry conducted/
Published scientific sponsored ~tudies NCI bioassay NIOSH
literature (unpublished) data data
4-Aminodiphenyl X
4-DimethylanLinoazobenzene X
4-Nitrobiphenyl X
4 4'Methylene bis X
(2-chioroaniline).
~hloroprene + x
Dibromochloro propane . X
Ethylene Dibroside + X X
Isopropyl Alcohol + X
-possible cancer threat
in the manufacturing
process-
Tetrachioroethylene + X
*NIOSH Recommendations
+Stated as ~ potential for cancer
PAGENO="0061"
55
Mr. Moss~ I would ask if your use of the figures $2 million in reading
the second paragraph on page 4 of your statement was an inadvertent
error or a deliberate correction.
The statement says: "$200 million."
Mr. BAlER. Yes, that figure is correct.
Mr. Moss. The Chair recognizes the gentleman from New Jersey,
Mr. Maguire.
Mr. MAGtTIRE. Mr. Baier, what do you recommend be done by
workers in the workplace to minimize their exposure to this cancer~
causing substance?
Mr. BALER. You mean the two specific chemicals or the one specific
chemical?
Mr. MAGUIRE. Yes, 2,4-diaminoanisole.
Mr. BALER. In our Current Intelligence Bulletin we were primarily
concerned that skin contact be avoided and that any exposure to the
mist or the material itself be avoided.
Mr. MAGUIRE. You do that by what-putting on a pair of golves,
for example?
Mr. BALER. Yes.
Mr. MAGUIRE. Some kind of suit that protects you?
Mr. BAlER. It could be.
Mr. MAGUILE. You make sure that you do not breathe in any of the
vapors; is that correct?
Mr. BALER. There are a number of respiratory protective devices
that are used in industry. There are also others that are used in
operating rooms. These are slightly different. The designs are different.
We were not thinking of a diver's mask or anything like that.
Mr~. MAGUIRE. I would like to know what you were thinking of.
Mr. BALER; All right.
Mr. MAGIJIRE. What would be appropriate?
Dr. PAGE. As a practical measure we would avoid skin exposure by
the use of gloves for the cosmetologists and hairdressers and perhaps
provide s&me protection tO minimize exposure to customers or clients
and so on.
Mr. MAGUIEE. You already have them ill.
Dr. PAGE. This would be to prevent exposure-unecessary exposure
to the skin of the clients also.
Mr. MAGUIRE. This is the point I was getting to. If we have 400,000
workers that are exposed in a ~ay which you regard as potentially
hazardous to them and you recommend that they wear gloves, and not
allow any of it to touëh their skin, et cetera, the thought that occurs to
me is that of~ course we have tens of millions of women all across the
country-and some men-who put hair dyes on their scalp and their
skin as a result of applying it to their hair.
Presumably that is also .a serious matter; is it not, if the scientific
data, on the basis that you have acted, are such as to suggest that
workers should be protected. Surely the general public should also
be; would you not think so?
Mr. BAlER. Yes.
Mr. MAGUIItE. What happens when OSHA receives a Current
Intelligence Bulletin? Are they able' to act or do they, in fact, act
when they receive such an intelligence bulletin from you?
PAGENO="0062"
56
Mr. BAlER. We have a very close working relationship under the
Occupational Safety and Health Act with the Occupational Safety
and Health Administration. We try to conduct regular meetings to
discuss policy issues and regular meetings of staff at the working level
of both agencies.
When we first hear of a problem, we communicate with representa-
tives of OSHA.
As we progress and transmit the Current Intelligence Bulletin to
them, we are in a position then to at least work together to develop
some kind of a proposed standard.
This has been done in several instances that we can enumerate
such as acrylonitrile and the 14 carcinogens which they now regulate.
There was a close working relationship where we reviewed the exist-
ing data together.
I cannot speak for how they will take any Current Intelligence
Bulletin.
Mr. MAcwIRE. Perhaps you could tell us what precisely has oc-
curred since you made the data on 2,4-diaminoanisole available in
Deceiiiber and formalized it in a Current Intelligence Bulletin in
January.
Mr. BAlER. We have transmitted it as an official-
Mr. MAGUIRE. There have been no meetings to follow up on that?
Mr. BAlER., Not yet.
Mr. MAGUIRE. Do you anticipate there will be?
Mr; BAlER. Yes, I would anticipate there would be.
Mr. MAGUIRE. Have any meetings been scheduled?
Mr. BAlER. Not at the present time.
Mr. MAGUIRE. Would it be a safe assumption to think that at the
conclusion of this hearing a meeting might be scheduled?
Mr. BAlER. Routinely we meet monthly, so that will come up at
our next meeting.
Mr. MAGTJIRE. This is a routine matter?
Mr. BAlER. No, I said routinely we meet-monthly-and this
would be one of the items on the agenda at the next meeting.
Mr. MAGUIRE. You were here for the hearing this morning; were
you not?
Mr. BAlER. Yes.
Mr. MAGUIRE. You are then aware of the new information pre-
sented today from NCI about the possible presence of other carcino-
gens, in addition to the 2,4-diaminoanisole in hair dyes?
Mr. BAlER. Yes, I am.
Mr. MAcwIRE. What are your intentions with respect to those
additional substances in hair dyes? Are you planning to publish
more bulletins? Do you have data which you regard as adequate
upon which to act? What is the current status with respect to those
additional cancer hazards?
Dr. PAGE. We have not yet received this information from NCI,
but when we do, we will determine the presence of these other com-
ponents In hair dyes. Upon such a review I would guess that we will
either issue another Current Intelligence Bulletin or attempt to
addressed the problem of hair dye components in general. We have
not had an opportunity to review any of the other data at this
point.
PAGENO="0063"
57
* Mr. MAGIJIRE. One final question.
Mr. Moss. We will have to suspend at this point. We will suspend
until 5 minutes after the last record vote. We have a series of recorded
votes which will now take place on the House floor.
It would be my judgment that we will be about 25 minutes, but
nevertheless it will be 5 minutes after the last vote is taken.
The subcommittee will stand in recess.
[Brief recess.J
Mr. Moss. The subcommittee will come back to order.
Mr. MAGUIRE. Mr. Baier, I read section 601(a) from the Food,
Drug, and Cosmetic Act to Dr. Upton and asked for his comment on
it.
Mr. BALER. I remember that; yes.
Mr. MAGUIRE. Then I will not need to read it again. I would like
to know if there was any justification for excluding coal-tar hair dyes
as the one and only exclusion under the law from the process of
determining safety.
Would you see any justification in that exclusion? I admit to you
that Congress wrote it. It is in there because the Congress of the
United States decided to put it in, not because of anything your
agency did or anything anybody else proposed.
Mr. BALER. We were discussing that. Actually, we see no justifica-
tion for excluding them because you can synthetically manufacture
chemicals which look like coal-tar chemicals also.
Mr. MAGUntE. Do you plan any additional studies to determine
the possible effects of carcinogenic substances in hair dyes on workers'
health? Are there any other studies `contemplated at this point other
than those that have been conducted?
Mr. BALER. The role of NIOSH is much different from that of NCI.
We are looking at occupations and trying to characterize exposures
to either hazardous chemicals or hazardous physical agents within
those occupational groups.
Mr. MAGUIRE. You will not yourselves conduct the study or any
further studies?
Mr BALER Not along the lines that you were just discussing That
is more in the realm of NOT.
Mr. MAGUIRE. What about epidemiology?
Mr. BALER. That is different.
Dr. PAGE. I might like to talk about this also.
At this time we are attempting to find an additional study popuh~-
tion, like hairdressers and cosmetologists, to do a more definitive
epidemiolo~ical study.
In addition, we are looking for a cohort or a group of workers who
are exposed to even higher levels, like formulators of hair dye prepara-
tions, to see if they could be entered into an epidemiological study.
We also have another study in mind. It is not a~Iong the line of
carcmogenicity. There is some concern also, for stillbirths. and birth
defects So, NIOSH is attempting to study this aspect This would be
done by an interagency agreement, perhaps with the National Center
for Health Statistics..
Mr. MAGTYIRE. Do you have any projected completion dates for
any of this work?
PAGENO="0064"
58
Dr. PAGE. No. We first have to look at the population for study
before we can actually lay plans for the experiments or studies.
Mr. BAlER. What we may try to do also is to characterize exposures
to various things within, let us say, the workplace of the cosmetolo-
gists.
Mr. MAGTJIRE. The image keeps returning to my mind of someone
workitig on someone's hair and having to wear gloves in order to
prevent any skin exposure. Then there is, of course, the person on
whom the work is being done and who is protected in no way whatso-
ever.
That is an image which ought to at least be an~ilyzed very carefully
by this committee and by the relevant Government agencies.
Do you have any final comments on any of the questions or any
other observations that you would like to make which have not been
elicited thus far?
Mr. BArER. There is one thing that I would like to bring out.
We have mentioned a current intelligence bulletin several times.
I think it might be worthwhile to at least put into the record just
what that is.
Fundamentally it is just an informational piece. We say: "Here is a
problem that we want to bring to the attention of various people."
We tell why we have a concern for a particular substance or a process
or whatever it might be.
If it is a chemical, then we give some indication of who makes it
and what the risks are, what kind of occupations these people have,
how many of them there are and that type of thing. Then we give
some idea as to what you might do in the meantime.
It is just a quick mechanism to get information out of the files and
out of the "in box" so to speak, and into the mainstream of things.
Mr. MAGUIRE. Does that get released to the. press?
Mr. BArER. Yes. The press does get copies.
Mr. MAGUIRE. Thank you very much, Mr. Chairman.
Mr. Moss. The Chair recognizes Mr. Segal, counsel for the com-
mittee.
M~. SEGAL. Mr. Baier, I would like to ask just one or two more
questions about the 2,4-diaminoanisole and then the ethylenedichloride.
Mr. Maguire asked about the epidemiology. You indicated there
were further studies gOing on. Do you feel those studies cited in your
report, current intelligence bulletin are significant studies to de-
termine that the safety is in question?
You mentioned conflict in your report, that is, in your presentation.
Could you comment on the conflict and how you intend to resolve
it?
Mr. BArER. Yes.
The current intelligence bulletin has quite a long list of references.
One of the two NIOSH studies that we referred to is not a final
report. They represent preliminary indications that there might be a
problem. They should be viewed as surveillance techniques, to select
areas for more in-depth evaluation.
Dr. Page, would you want to add some more?
Dr. PAGE. I do not have anything to add at this point.
PAGENO="0065"
59
Mr. SEGAL. Would you say that the epidemiology at this point was
not the main reason which led you to put out this statement to inform
the American public that this is a potential danger?
Mr. BAlER. As I mentioned in what I said about the current intelli-
gence bulletin, it is an alert mechanism to bring out that there may be
a problom here. Certainly we will gather more information. There will
other sources of information coming to us. There are tumor registries
that we may want to look at. We may want to compare types of tumor
registry cases with specific occupations. This is an on-going surveillance
effort.
A surveillance effort is simply looking for problem areas.
Mr. SEGAL. What about the other scientific evidence? The Ames
test showed mutagenicity. Do you consider that significant?
Mr. BAlER. Yes, but I would rather Dr. Page discuss that.
Dr. PAGE. I think with the combination of the mutagenicity test
and the bioassay test results, we do have some evidence that is sub-
stantial for the potential ftir carcino~enicity. It does not necessarily
mean that it really will occur, that is, that cancer will be found in
high numbers in the th~posed human population.
But my own personal opinion is this. Even without the epidemiolo~-
ical data, there is sufficient reason to be concerned, and I feel it
warrants the current intelligence bulletin.
Mr. SEGAL. So that would be the Ames test, that is, the tests on the
fruitfiies and what else? The laboratory tests on absorption? Are you
convinced that application externally results in absorption into the
human body; is that right?
Dr. PAGE. Yes, I think the data which has recently come from the
Food and Drug Administration points out that absorption is certainly
possible with this chemical. So, on that basis, you have to be concerned
for the internal distribution of the chemical within the body and
possible carcinogenicity of internal organs.
Mr. SEGAL. We also heard and received information this morning
that there were several other chemicals, depending on bow many you
counted, as many as eight additional ones involved in aspects of
hair dyes.
Do you have similar information that might lead you to addi-
tional intelligence bulletins?
Dr. PAGE. At this time I am not aware of having this information
in NIOSH.
Mr. BAlER. We have a list of chemicals that are used.
This is why I mentioned to Mr. Maguire that we may want to
characterize just what exposures the cosmetologist is subject to.
We have sponsored a number of surveillance studies and one that
comes quickly to~ mind is a death certificate study over a 20-year
period.
In this study we found that workers in certain occupations tend to
die of a similar cause. So then we have to go back into the working
environment to find out what is in there that could trigger off that
effect.
So, this now is really the initial blush of the problem, so to speak,
and by looking into what is in that work site in depth, we will have a
much better appreciation for the chemicals that may be present.
24-600 Q . 78 - 5
PAGENO="0066"
60
This is another reason why we also said in our statement, and we
also said in the Current Intelligence Bulletin, that we did not just
want an arbitrary substitution of other ehemicals until we know what
the effects of those are.
We are dealing with chemicals that take a long time from exposure
to ê~fects. We are talking about 15, 20, 25, or 30 years, even. These are
the kinds of problems we have. This is why we just do not want an
arbitrary substitution of a chemical. We do not want to have another
problem 20 years from now.
Mr. SEGAL. Switching for a moment from an intelligence bulletin,
namely the one involved in 2-4-diaminoanisole, to ethylene dichloride,
you published something different which was a criteria document.
Could you tell us how much more standing that has?
Mr. BAlER. A criteria document is just about all we know about
a chemical, group of chemicals or a process. It may also be a physical
agent or a safety problem. It is all we know about something at a
point in time, including a very thorough search and evaluation of
the available literature. From beginning to end we take from about
10 to 15 months to develop a criteria document and some take even
longer.
Since it takes time to gather all that information on a substance
and determine how to analyze it and what analyses of biological
specimens must be made and how to inform the worker and so on-
it is time consuming. Since we want to get some information out in a
hurry, we issue a current intelligence bulletin.
I guess what really triggered off the beginning of the Current In-
telligence Bulletin was when vinyl chlorlde first appeared as causing
angiosarcoma of the liver of exposed workers. We developed an emer-
ency report which we transferred to OSHA. They went for a temporary
emergency standard for vinyl chloride and proceeded with rulemaking.
So, this, I think, was the very first situation which brought to our
attention the need to responed quickly to a new problem which in
turn lead to development of Current Intelligence Bulletins.
Mr. SEGAL. With reference to ethylene dichioride, you issued the
criteria document in March 1976, recommending a change in the stand-
ard of 50 parts per million down to 5?
Mr. BAlER. But it was based on the. effects on the liver and cardiac
effects and not on cancer. It was only recently that we learned there
was a potential for carcinogenicity. We are still waiting for a final
report from NCI. And, if, in fact, it is a carcinogenic chemical-and I
understand from this morning that it is-then we will proceed to rec-
ommend to OSHA even more stringent controls.
Mr.~$EGAL. How often does OSHA take your recommendations? I
take itin this particular. instance, which has been since March 1976-
which. is almost 2 years-that you made your previous recommenda-
tion. Has that been incorporated?
Mr. BAlER. No, it has not.
Mr. SEGAL. What is your batting average with them?
Mr. BAlER. I guess we have transmitted in the neighborhood of 80
criteria documents. I do not know really what the actual number of
standards are; maybe 5, 6, or 7; somewhere in that neighborhood.
Mr. SEGAL. Five of the 80 have been implemented?
PAGENO="0067"
61
Mr. BAlER. Promulgated into regulations.
Mr. SEGAL. So less than 10 percent would be a safe, guess?
Mr. BAlER. Oh, yes.
Mr. SEGAL. It is not appropriate to ask you why or should we ask
them that when they come?
Mr. BATER. We are in hEW. They are part of the Labor Depart-
ment.
Mr. SEGAL. That is all I have, Mr. Chairman.,
Mr. Moss. Mr. Wunder?
Mr. WUNDER. Mr. Baier, I would like to direct your attention to
page 4 of your statement wherein you mention two epidemiological
studies.
Would those studies be "A Retrospective Survey of Cancer in
Relation to Occupation" by P. De~oufle, et al., and "Occupational
Characteristics of Disabled Female Workers: A Descriptive Study"
by Kennedy and Spirtas?
Mr. BAlER. Yes.
Mr. `WUNDER. Are those the same two studies that are mentioned
in your mtelhgence bulletin dated January 13, 1978?
Mr. BAlER. Yes.
Mr. WUNDER. Mr. Chairman, at this time the clerk has two doc-
uments that I would ask be passed out to. the Members `and to the
witnesses.
Mr. Moss. Without objection, these documents will be placed into
the record at this point.
[Testimony resumes on p. 76.]
[The ma~erial referred to follows:]
PAGENO="0068"
62
Yale'University New Haven, Connecticut 06510
January 20, 1978 SCHOOL OP MEDICINE
333 Cedar Street
Mr. Conner Fay Robert W'ood Johnson
Vice President, CLAIROL Clinical Scholar Program
345 Park Avenue
New York, New York 10022 ALVAN 5. FEINSTEIN, M.D.,
Program Director
Dear Mr. Pay: (203) 436-8787
As I indicated to you by telephone, Learn writing these comments as a Professor
of Epidemiology who is interested in the reputation of my profession,' and who is
cOncerned about the way in which statistical data can be abused to the detriment of
the public. I do not wish to receive, and shall not accept, any personal stipend
for setkding you these comments, which you are free to use in any way you wish. At
some fUture date, however, I nay want to incorporate these remarks in a paper I shall
prepare for submission for publication in a scientific journal.
I am commenting on two documents:
I: "A Retrospective Survey of Cancer in Relation to Occupation" by P. . Decoufle,
K. Stanislawczyk, L. Houten, I.D.J. Bross, and E. Viadana. Contract No. HSM 99-13-5.
Issued as a NIOSH Research Report, by the U.S. Dept. of H.E.W.
II: A manuscript marked "DRAPT, Preliminary Report" and titled "Occupational
Characteristics of Disabled Female Workers: A Descriptive Studyby .1. Kennedy and
R. Spirtas, of N.I.0.S.H., Cihcinnati.
My comments are as follows:
I. "Retrospective Surv~py..." by Decoufle et al.
The authors used the "case-control" technique to conduct essentially 22
studies. In each study, the "cases" consisted of patients found at Roswell Park
Memorial. Institute to have a cancer in one of twenty-two different sites, during the
period 1956 to 1965. The "controls" consisted of patients referred to the same
Institute and found to have "non-neoplastic" diseases. For all cases and controls,
the investigators compared the prevalence of 72 different occupations as pà'ssible
etiologic agents. In standard performance of such studies, an odds ratio (which the
authors incorrectly call a "risk ratio") would be calculated for the presence or
absence of that occupation.
The standard table would be as follows:
NO. OF PATI TS WITH
CANCER NO CANCER
Pts. Having
Suspected a b
Occupation
Pta. Not Having
Suspected c d
Occupation
PAGENO="0069"
63
Mr. Conner Fay 2 - Januavy 20, 1978
The odds ratio would be calculated as (axd)*(bXc), If the odds ratio *~ceeds 1,
with a P value that is statistically significant, and with a 95% donfidence interval
that does ~ include 1, the result suggests an elevated risk for that occupation
for the selected cancer.
In the procedure used by these investigators, the suspected occupation
was not compared against its absence. Instead, the investigators used "clerical jobs"
as the comparative group.
The remaining procedures used by the authors have the following gross flaws
and fallacies:
j~ExPo5ure to Hair Dyes
Although the suspàcted etiologic agent is hair dyes, no effort was made
to distinguish whether the petsons occupationally labelled as "Hairdressers and
cosmetologists" actually used or were exposed to hair dyes. Since the category in-'
cludes electrologists, manicurists, beauty school teachers, shampooers, etc., the
quest for scientific evidence would have included an inquiry to determine whether the
patients were in fact exposed to hair dye.
2. - Risk and "Dose" 0. E~oøuF5
`A second important item of scientific evidence in such studies is the
dose-response curYe Was the risk of cancer greatet in people who bad used hair
dyes in large amounts or for longer durations of employment? The investigators made
no effort to obtain such evidence.
3. Capricious Statistic~
When 22 different cancers are examined for 72 different occupations, a
great many "positive" or "significant" relationships can be expected to occur capri-
ciously by chance alone. In fact, using a P level of .05 for "statistical significance
during the examination of 1584 (..72x22) tables, one would expect to find 79 relation-
ships (~l584x.O5) that emerge as "statistically significant" even if there is actually
~ association between any of the occupations and any of the cancers. On pages 6-9,
the authors mention some of the many Other "significant" relationships they found
dug~Lng the multiple statistical analyses.
To guard against these caprices during "data-dredging" research of this
type, cautious investigators customarily make stringent demands before accepting a
* relationship as "statistically significant". Although the stringency will vary accord-
ing to different principles, many careful investigators -~ aware of the "multiple
comparison" problem - would insist on P values, below * 001 before calling any of these
* relationships "significant". Some investigators might demand P values that are even
smaller.
The current investigators, however, were willing to assign statistical
significance to grossly over-inflated P values,, at levels (of .01 to .05) that are at
leaSt ten times, and perhaps 100 time~,larger than they ~b~uld be for decision-making.
4. Confidence Intervals
When euffiOientiy large numbers of `people are investigated, almost any
PAGENO="0070"
64
Mr. Conner Pay - 3 - January 20, 1977
statistical test of random probability will yield a "significant" resuld. for this
reason, knowledgeable epidemiologists always test the ~redision of an odds ratio by
calculating a 95% confidence interval around it. This process involves calculating
the "standard error" of the odds ratio, and using the formula .0 ± .1.96 x s * e. (0),
where 0- odds ratio, and s.c. (0) - standard error. In the formula given by 3 .L.
FleiSs on page 66 of his standard textbook, "Statistical Methods for Rates and Pro-
portiocs", if the four cells of the table are a, b, c, d, the odds ratio, 0-adxbc;
and ____________
s.c. ~
In Tables marked "C" and "D" on pages marked 160 and 176 in the material
avail.able to me from this report, the investigators provide the data that allow
confidence intervals to be calculated for "hairdressers and cosmetologists" for the
diverse cancers, including the three ("ovary, uterus, and lymphomas") that are par-
ticülarly "indicted" on page 7 of this report. A re-appraisal of these data does
not confirm the results claimed by the authors and does not support or sustain any
of the "indictments". In all tl3ree instances, the 95% confidence interval around
the odds ratio includes the value of 1. In cancer of the ovary, for example, the
confidence interval runs from .071 to 5.11, indicating that the "true" risk ratio
may even be as low as .071, which suggests that the occupation has a "protective"
effect against ovarian cancer. Furthermore, in corpus uteri, the odds ratios
offered in the tables (values of 3.00 and 2.82) are incorrect. They are much lower
(in the range of 1.5) and the results are ~ statistically significant by the
chi-.square test. In lymphomas, the tabulated data on pages 55, 61, 3.60, and 176 show
nothing significant~ and do not sustain the claim made on page 7 of the text. (I can-
not understand why the occupation is said to have "unusual cancer experience" with
lyznphomas.)
5. The Assembled Group
Only for a reader who leaves the investigators' discourse to look at the
actual. data does it become apparent that the entire occupational indictment here is
base~ on a total series of at most 97 hairdresser-cosmetologists among the entire
"25,416 individuals" admitted for Suspected tumors to Roswell Park Institute dqring
l956-1.965~ The 6 uterine cancers, 10 ovarian cancers, and 5 lymphomas fàund in those
i~f'ha1rdressers constitute the total number of cancers on which all these conclusions
are based. No useful statistical analyses can be performed when the numbers are so
tiny and when the series of patients is so non-representative of any defined group.
II. "Occupational Characteristics,.." by 1(ennedy and Spirtas
This paper, which the authors label a "descriptive study", contains a
listing of the "proportional morbidity rates" for different conditions in different
occupational groups, as noted for women receiving Social Security Worker Disability
Allowances during 1969-1972.
People doing "Administration" and "Education" had the highest rates of
"neoplasms". Their respective values of 153 and 148 were about 20% higher than the
126 noted for cosmetologists. Other partitions are used for other neoplasms and
.conditions. No data are supplied to denote how many people were examined in each
category; or the biases in occupation associated with submission of social security
In the particular comparisons performed for the three `main' cancers, at most 37
"hairdressers and cosmetologists" were included.
PAGENO="0071"
65
Mr. Conner Fay January 20, 1978
claims; or any other elemental requirement of objecti~Ye, careful scientific reporting.
For example, the authors do not indicate that their category of "cosmetologists"
includes barbers, masseurs, and beth attendants, as well as embalmers. The authors
also make no cousnent on the strikingly high rates of disability found, for cancers
and other major ailments, in the occupations of education and administration.
* * *
In sumeary, I am astonished to learn that eltbet one of these ~two reports has
been regarded as an "epidemiologic study". I cannot think of any epidemiologists,
who respect either themselves or epidemiologic science, who would want to ~be associ-
ated with either study; or who would give either study any scientific credibility.
In fact, I look forward to disseminating both these projects to students, so that they
can see excellent examples of bad research and what to avoid in doing "epidemiologic
studies". The second paper has such poor organization, content, and quality that it
would be unacceptable as an essay project from a first~'year graduate student.
The first of the two papers has better form; and shows at least a minimal regard
for presentation of data - but here too, the investigators have violated almost
every scientific stanaard that would be required for research to be regarded as
objective, reasonable, and worthy of attention.~
As a taxpayer, I am distresSed tb find NIOSH supporting work that is so poor that
whatever is fount cannot be believed. La an epidemiologic scientist, I am appalled
that the title o* "epidemiolo'gi~ study" has been applied to "research" of such extra~
ordinarily low quality.
Sincerely yours,
Alvan 1. Feinstein, M.D.
Professor of Medicine
and Epidemiology
ARP:abn
PAGENO="0072"
66
THE JOHNS HOPKINS UNIVERSITY
School of Hygiene and Public Health
Department of Epidemiology
615 North Wolfe Street
Baltimore, Maryland 21205
TO: Dr. John Menkart, Clairol, Inc., 2 Hlachley Rd., StSxnford, CT.
FROM: Irving I. Kessler, M.D., Dr. P.M., Professor of Epidemiology
DATE: January 21, 1978
You have asked me to evaluate the NIOSH Roswell Park Memorial
Ins1~ttute study, which was cited in the January 13, NIOSH
Current Intelligence Bulletin recommending that 2, 4-DAA be
handled in the work place as a human carcinogen.
Due to time limitations, my comments and observations are limited
to those portions of the NIQSH research report "A Retrospective
Survey Of Cancer In Relation To Occupation" which you provided.
These deal with general background, methodology, results, discus-
sion, summary findings, occupational groups studied, statistiøal
tables dealing with "hairdressers and cosmetologists" and the
technical appendix (pp. 1-15, 37, 55, 61,160, 176, 196, 197).
On the basis of my review of this information, I have prepared
the attached critique of the Roswell study. This covers both
general observations and those portions dealing with "hairdressers
and Cosmetologists" in particular. I understand you are sending
me the full NIOSH report, and I will, of course, advise you if
anything in the balance of the report necessitates revision of
my current evaluation.
CONCLUSIONS: The NIOSH finding that hairdressers and cosmetologists
show ~an unusual cancer experience for three sites: ovary, uterus,
and lymphomas" appears to be unwarranted for a number of reasons.
The cancer patients seen at the Roswell Park Memorial Institute
are, by the investigators' own description, highly Selected and
not necessarily representative of the universe of cancer patients.
Their definition of "hairdresser and cosmetologist" includes a
highly heterogeneous group of women lumped together into a single.
risk category. Certainly.many of them do not work with hair dyes.,
For these women in the so-called "hairdresser and cosmetologist"
category, the actual number of cancer cases was very small, and,
in th~ authors' own words, "A seemingly high relative risk based
on only a few cases should be interpreted cautiously."
DISCUSSION: Utilizing self-recorded occupational information
~btained from a group of cancer patients seen at one highly
PAGENO="0073"
67
Dr. John Menkart
January 21, 1978
Page2
selective cancer hospital, the investigators suggest that cancers
of the ovary, corpus uterus, and lymphoma are associated with the
hairdresser and cosmetology industry Their conclusions are
probably unwarranted for a number of reasons. These include the
following: S
1) The cancer patients seen at the Roswell Park Memorial
Institute are acknowledged by the investigators to be
highly selected, rather than representative of the
universe of cancer patients;
2) The investigators' definition of the hairdresser and
cosmetology industry was highly non-specific. Included
in this category were cosmetology consultants, electrolo-
gists, wig stylists, beauty culture teachers, as well as
managers and owners of beauty parlors. Thus, a highly
heterogenous group of women exposed and not exposed to
a widevariety of beauty products were lumped together
into a single risk category;
3) The occupational histories were recorded by the patients
themsei,ves, Such self-administered questionnaires are
suspect to some extent because of the wide variety of
women filling them out. These would include women
varying in intelligence, social class, and language
ability, as well as their motivation to fill in the
answers and to fill them in completely;
4) More than one-half of all the recorded occupations were
not included in the analysis or were lumped into the
control category on the basis of a prior assumption that
"clerical occupations are relatively free of health
hazards," I Yet some of the occupations excluded, such
as "misce]7laneous crafts," and "laborers,." might well
have been,hazardous ones;
5) Occupatio~s for which duration of employment was unknown
were arbitrarily excluded and no information offered~ as
to the number of such patients;
6) ~or womer in the hairdresser category, the actual numbers
of cancer cases was so small as to make impossible an
analysis which would control for the large variety of
potential confounding factors which might very well have
explained the observed results. Only age Was adjusted
for in mOst of the analyses and, even this, only in
terms of a rough dichotomy between women under 60. and
60+. No documentation was offered in regard to the
specific age comparability of the cancer cases and
control.
PAGENO="0074"
68
Dr. John Menkart
January 21, 1978
Page 3
None of the criticism leveled against this study shduld in any
way be construed as criticism of the professional abilities of
* the investigators, a number of whom are colleagues personally
known to me. Rather, it is my intention in this critique to
* direct further attention to the limitations inherent in this
study, many of which are fully described by the investigators
themselves in their discussion.
IXK/kp
Dictated, but not read.
Attachment
PAGENO="0075"
s~ntar: `fuesday aornlnZ, April $
?p~Jeleage: W~~NESDAY AM's, April 6
EXCER~ED FI~OM:
DIPHTHERIA-VACC
~ALuATToN~
E. CUYLER HAMMOND, .Se.D. (64), Vice President for Epidemiology aid Statistics,
American Cancer Society. Dr. ESamond was born in Baltimore, lid., and received
his Doctor of Science degree (Sc.D.) from Johna Hopkins UniverSity. Es j~oLned
the American Cancer Society in 1946 after serving in the U.S. Army Air Force as
Aset. Chief of the Statistics division, office of the Air Surgeon. Prior to this
he served four years with the Division of Industrial Hygiene. Dr. Hammond also
is adjunct professor in coimounity medicine, Mt. Sinai School of Medicine; a
member of the scientific advisory panel of Research to Prevent Blindness * Inc.;
associate editor of Enrironsantal Research; advisory editor of ~a~k Cancer Journal
for C1ii~4apa end a member of the Board of Directors and past president of the
New Vora~ Academy of Sc~1.,wm,.
AMERICAN
CANCER
SOCIETY
, i~iws SERVICE
770 YNIOD AV$NU$
#40* Y000* N.Y. 10011
1212? 371.2000
(V
69
1nerican Cancer Society's
NINETEENTH SCIENCE WRITEPS' SEMINAR
Sarasota Hyatt House
Sarasota, Florida
Aprtl1~. 6, 3.977
F
I
TETANUS AND
SOME NEGATIVE FINDINGS (POLIO. SMALL FOX..
a~ Rrctc
PAGENO="0076"
70
SOME NEGATIVE FINDINGS
(POZIO~ SMALL POX, TETANUS AND TRERIA~VACCINES; BEAUTICIANS)
AND EVALUATION OF RISKS
E. Cuyler Hanmtond, Sc.D.
.extreme
t..,the-othex.
S~rne people are alarmed, to a far greater degree than is~
~ They fear to eat anything
but natural food grown without man~made fertilizers and insecti~~
cides and with nothing added later. They think that air pollution
will cause them to die of cancer as will contact with rt~anifold
products of industry. They do not ask "what is harmful?" They
ask "what, if anything, is safe?"
Sone workers are fearful of losing their jobs in these
tines of ~inemployment. For example, a friend of mine, who had
reason .to suspect that a certain substance with which he woçks
is Carcinogenic, recently said to us: "For God sake don't ~
that it causes cancer. If you~do, it will be banned and 1
will lose my job. At my age, I will never be able to find any
other decent job." This is n~t an uncommon attitude.
PAGENO="0077"
71
`Hammond
page. 2
A growing number of people are becominq annoyed if not ~engry
abotit the whole affair. .
"What are they going to prohibit next? Sex?"
Many of these people express the opinion that government and
scientists should stop their meddling and leave people alone.
They are also becoming highly skeptical of pronOuncements made
by "authorities" including medical and scientific "authorities"~
U this attitude becomes widesprea&, it will seriously endanger
our efforts to control cancer.
It is not our object to frighten people. It is not our'
object to pu~ people out of work; and it is certainly not our
object to take all pleasure out of life. Our object is to reduce
the risk of cancer in so far as it is feasible to do so. Feasibility
depends upon many elements, not the least of which are public
attitudes.
~ real~siâ `attitudes is
t~.,frankty admit the `limitations `in our present knowledge and in
~ `we" know' and
wb~t"we"oriIy S~~bCt''And when we speak of rIsk, express the
degree of risk in terms which are meaningful to the, average person.
exc.iting.~and receive wide attention in both the scientific press
and public news media.' Negative findings - those which seem to
PAGENO="0078"
72
Hammond
page 3
show that a substance is hazm~ess - tend to be dull and there..
fore usually receive little attention. Poth~s~-reason1Iwil3~
s4art by describing several hegative findings. They are~ of i~n~
Verest on3~y in that they tend to counteract unwarranted fears.,
Beauticians
There has been speculation that some, and perhaps many,
of the various chemical agents used by or on women for beauti-
fication are carcinogenic. This has caused worry among many
women especially among those most heavily exposed: beauticians.
Epidemiologic evidence is now available on this matter.
Over 1,000,000 men and women in 25 states were enrolled
in a long term study by volunteer workers of the American Can-
cer Society. Upon enroliment, each of them answered a lengthy
queètionnaire. ?~dingspreeented below are based upon data
a~vailable after 13 years of trabing.
Of some 589,000 female sub4ects all of whom were over
the age of 30 and most of whom we~e over the age of 115 at the
start of the study - 5,125 said that they were beauticians.
By the matched group procedure, we matched the beauticians with
non.~be;uticians on age, race, education, place of residence
(large metropolitan area vs rural or less populated area),
amount of cigarette smoking, past history of cancer, and past
history ofheart disease.
Matches were found for 5,117 of the 5,125 beauticians.
In most. instances, many non-beauticians were found as matches
for each of the 5,117 beauticians. This. increased the `statis-
tIcal, stability of the findings.
PAGENO="0079"
73
Hammond
Page Ls~
Durinj the course of the study, 32]. of the beauticians died,
Adjusted for the size of the two groups and standardized for age,
351 of the~beauticians died, This small difference (in favor of
the beauticians) is not statistically significant. 113 of the
beauticians died of cancer, Adjusted for size of the two groups,
115 of the non~~beauticians dIed of cancer. T1s~vtrti~a11y
nodlfferenee. There-was not a single site of cancer from which
s~nificant1y more beauticians than non.-beauticians died.
The findings were essentially the same during each of
twelve successive years of tracIng.
IC..~xposure_as&oci~ate&.with-..the occupation of beautician
has resulted in an increase in death rates from cancer of any
s~terthe increase is too small to show up in a study of over
5~,OOO people over a period of 13 years~
It could be that some "beauty aid" introduced in recent
years is highly carcinogenic but has not been used sufficiently
long for the effects to become apparent, Therefore~in spite
of our findings, I belIeve that all recently introduced "beauty
aids" (and those proposed for introduction) should be tested
for possible carcinogenic effects.
Polio Vaccine(SV~O)
Research carried out by virologists between ].9514 and early
1961 revealed that some batches of polio vaccine produced up to
that time were contaminated with living sImIan virus 1~O (SV 140).
(Later, leading virologists told me that they thought that most
if not all of the batches produced up to that time were at least
PAGENO="0080"
TABLE I
PROBABILITY OF SU?.VIVING TO AGES 65 AND 75
AND LIFE EX?ECTANC~ FOR U.S. WHITE MALES STARTING AT AGE 20
a) If Death Rates are Increased from hge 20 on by:.
b) If Death Rates are Increased from Age 40 on by:
U.S.
White Males
1974
1%
2%
Prob.
Surviving
from
-
Age 20
to Age 65
(%)
70.73
70.49
70.24
. Prob.
Surviving
from
Age 20
to Age 75
(%)
44.13
43.77
43.41
Life Expectancy
at Age
20 (yrs.)
50.95
50.83
50.71
5% 7% 10%
69.52 69.03 69.32
42.35 41.66 40.64
50.39 50.15 49.83
15%
67.14
39.00
49 * 31
25%
64.85
35.91
48.34
U.S.
White Males
1974 1%
Prob. Surviving from
Age 20 to Age 65 (%) 70.73 70.52
Prob. Surviving from
Age 20 to Age 75 (%) 44.13 43.79
Life Expectancy
at Age 20 (yrs.) . 50.95 50.85
50%
59.44
29.19
46.23
50%
60.60
29.76
46.93
200%
35.16
8.31
38.36
200%
*37.98
8.98
40.61
2%
70.30
43.44
50.75
100%
49.93
19.26
42.93
100%
51.88
20.02
44.22
5% 7% 10%
69.65 69.22 68.58
42.43 41.77 40.80
50.45 50.26 -49.98
15%
67.53
39.22
49.54
25%
65.47
36.25
48.71
PAGENO="0081"
TA!3LR II
PERCENT OF DEAT!13 FROM 2~LL CAUSES
FOR SELECTED cAUSES OF DEATh
0
h1hit.~ Ma1~s, U.S. 1974
CE CROUP
20-»=9 30-39 40-49 ~0-59 60-69 70-7~ SOf
(.~t~~Of Death ~
All Causes 100.000 100.000 100.000 100.000 100.0ü~ 100.OoO 10O.0~O
.~i1 ~ 6.649 11.010 18.727 23.~38 24.393 20.456 12.949.
ii'rg 0.122 1.997 6.819 9.319 9.214 6.107 2.240
C~1on-R..ctum 0.216 1.147 1.696 2.458 2.921 2.803 1.158
StXfl~..CiI 0.037 0.315 .0.750 G~879 0.~76 0.974 0.165
Livar 0.048 0.137 0.243 0.338 0.393 0,326 0.206
Pmcruas 0.041 0.366 0.929 1.346 1.321 1.108 0.654
* 0.011 0.014 0.130 0.570 1.511. 2.660 2.744
ti~idder 0.004 0.0U2 0.226 0.458 0.738 0.916 0.762
k~idncy 0.059 0.247 . 0.598 0.700 0.614 0.427 0.215
Lcukeittia 1.024 1.261 0.709 0.701 0.156 0.7~3 0.646
tt.Cl)t.~.'tE1C IIt~rt Diseasi
0.898 11.390 31.880 39.265 40.480 40.819 42.466
PAGENO="0082"
76
Mr. WUNDER. Mr. Baier, what you have been provided is first a
letter from Dr. Alvan Feinstein of Yale to a Mr. Fay of Clairol, and
second a memorandum from Dr. Kessler of Johns Hopkins, a professor
of epidemiology, to Dr. Menkart of Clairol.
I would like to read several portions of Dr. Feinstein's letter first
wherein he discusses those two studies that you conducted.
On page 4 of Dr. Feinstein's letter he says:
In summary, I am astonished to learn that either one of these two reports has
been regarded as an "epidemiologic study." J cannot think of any epidemiologists,
who respect either themselves or epidemiologic science, who would want to be
associated with either study; or who would give either study any scientific
credibility. S
In fact, I look forward to disseminating both these projects to students, so that
they can see excellent examples of bad research and what to avoid in doing
"epidemiologic studies."
The second paper has such poor organization, content, quality, that it would be
unacceptable as an essay project from a first-year graduate student.
Dr. Fernstein goes on to say:
As a taxpayer, I am distressed to find NIOSH supporting work that is so poor
that whatever is found cannot be believed. As an epidemiologic scientists, I am
appalled that the title of "epidemiologic study" has been applied to "research"
of such extraordinarily low quality.
I know that this is the first you have seen of these letters, but do
you have any immediate reaction?
Mr. BAlER. Fundamentally, there are different kinds of epidemi-
ologic studies.
Mr. WUNDER. What is the difference between the two?
Mr. BAlER. One is if we are just trying to identify trends as opposed
to an in-depth evaluation of the environment and its effects on worker
sickness and death. The former is the type of epidemiology that I
think is being referred to here.
The purpose of this study was simply to say: "Is there a problem in
certain occupations?" Primarily we were looking at females. A lot of
work has been published on males. Most standard mortality rates are
based on white males.
We do not have very good data on certain minorities, ethnic groups
or women. The purpose of these studies is simply to say: "How are
women~being affected as a result of their jobs?"
Then' from there you go into the more in-depth detailed study of the
type that Yale University could design, or that NIOSH could design.
Dr. Page, would you like to add to that or comment on it?
Dr. PAGE. I think the point that Mr. Baier is making is good. These
were more like surveillance studies of. population without really
trying to look at the specific cause first, rather than going into an
in-depth study for an association; for example, cancer in hairdressers.
So, it is pointing toward potential problems for further study.
Mr. WUNDER. I think the point is this. If you look on page one of
Dr. Feinstein's letter, I think he addresses that point in this sense.
He says:
As I indicated to you by telephone, I am writing these comments as Professor
of Epidemiology who is interested in the reputation of my profession, and who is
concerned about the way in which statistical data can be abused to the detriment
of the public. S
PAGENO="0083"
77
What Dr. Feinstein is talking about here is that you published the
results of these two studies and indicate that they suggest excess
cancer among cosmetologists and it would lead one to believe that there
is rather good information on it.
Do you have any comment on that?
Dr. PAGE. There is only one comment I would make here. That is to
counter to Dr. Feinstein's comments. These NIOSH reports, prior to
publication, were reviewed by a number of other epidemiologists.
They have had a critical review.
They do have deficiencies. NIOSH is not trying to cover these up
and say that they are definitive studies.
Mr. WTJNDER. How many cosmetologists were there out of this
25,000 sample? Would 97 be the right figure?
Dr. PAGE. I believe 97 is correct for the Roswell Park Memorial
Institute study.
Mr. WTJNDEE. Were all those actually people who would have
handled hair dye, or did they include such things as manicurists, wig
stylists, and the like?
Dr. PAGE. It was a broad category. There were others in there that
did not actually handle the hair dye. It is hard to separate out the
types.
Mr. WUNDER, Mr. Chairman, these two documents were just pro-
vided to the NIOSH witnesses. So, I wonder if we ~ould ask them to do
an analysis of Dr. Feinsteiii's, comments and have those submitted
for the record?
Mr. Moss. The record will be held open at this point to receive the
comments of the agency On the letter of Dr. Feinstein.
Without objection, so ordered.
[Testimony resumes on p. 88.]
[The following letter was received for the record :J
PAGENO="0084"
78
(~) ~ DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
f PUBLIC HEALTH SERVICE r~ `~
CENTER FOR D$SEASE CONTROL - -.
(JATIONAL NST~Tu'rE FOR
SAFETV~
5600
ROCKVILLE,
FEB 241978
The Honorable John H. Moss
Chairman, Subcommittee on Oversight
a4d Investigations
Committee on Interstate and
Foreign Comme~'ce
House of Representatives
Washington, D.C. 20515
Dear Mr. Chairman:
This is in response to the request from your Subcommittee regarding
comments from Dr. Irving Kessler and Dr. Alvan Feinstein on two NIOSH
stu~ies indicating that cosmetologists and hairdressers may be at
increased risk of cancer. In addition to responding to the specific*
comments these reviewers made on the two studies at the request of
Claix'ol, Inc., I vould like to discuss why NIOSH conducts these kinds of
studies.
The two studies in question, "A Retrospective Survey of Cancer in
Relation to Occupation," by P. Decoufle, et. al., and the preliminary
* report, "Occupational Characteristics of Disabled Female Workers: A
Descriptive Study" by Kennedy and Spirtas, were related to projects
* `within the Illness Effects Section of the NIOSH Surveillance Branch.
This section seeks to identify ocdupational groups exhibiting unusual
patterns of mortality or morbidity that may be related to hazardous
exposures in the workplace. Because there is no national system for
reporting occupational disease, NIOSH must `rely to a large extent om~
existing data bases in identifying high risk occupational groups. The
Decoufle study was based on data collected at Roswell Park Memorial
Institute, which specializes in cancer.research. The Kennedy and
`Spirtas study was based on data from the Social Security Administration
file of awards to disabled workers. The costs of such studies are
relatively small. The contract cost for the former study was $96,Qoo
and the interagency agreement to assemble data for the latter study was
$6,000.
The techniques NIOSH used in these hypothesis-generating studies are
well.established in the fields of occupational and environmental health.
Similar studies include a 1950 Occupational Mortality Study on Males
(Guralnick, NCHS), the 1959-1962 Disability Study on Male Workers
PAGENO="0085"
79
~P~ge 2 - The Honorable John H. Moss
(Occupational Health Program, P115 and the Bureau of Disability
Insurax~ce, SSA), and the Registrar General's Report (England and Wales).
Recently, the occupational and environz~ental health scientific community
made statements that support and recommend more research of this nature:
(1) Environmental Monitoring, A Report to the U.S. EPA from the Study
Group on Environmental Monitoring, Committee on National Statistics,
Environmental Studies Board, Numerical Data Advisory board, Assembly of
Mathematical and T'bysieal Sciences, and the 1~ational Research Council;
and. (2) Report from the .NIOSH Task Force on Occupational Health
Surveillance.
It is important to keep in mind ,that the NIOSH Current Intelligence
Bulletin 19 on 2,k-Diaminoanisole clearly states that although the two
NIOSH studies suggest an association between cancer and employment as
cosmetologists, the studies did not attribute any exceSs incidence of
cancer to exposure to hair dyes.
Enclosed is our response to some of the main points raised by Dr.
Feinstein and Dr. Kessler about the NIOSH studies..
Sincerely yours,
~ ~
.»=~ [J. Donald M$lar, M.D.
( Assistant Smfrgeon General
-. -. Acting Director:
2~Epclosures -* - -
PAGENO="0086"
80
EESPONSE TO DR. KESSLER' S COMMENTS ON ROSWELL PARK. STUDY
ISSUE:
The pa1~ients seen at Roswell Park Memorial Institute (RPMI) are~not
representative of cancer ~atie~its generally.
RESPONSE:
Patient non-representativeness would introduce bias if Roswell cancer
patients were compared with cancer patients outside R?MI; however, in
the Study they were compared with R?vlPI non-cancer patients. As
stated on page 5 of the NIOSH report, "These phenomena, due to
referral patterns characteristic of a single hospital do not necessarily
introduce significant bias in the analyses presented here as long as
there are no systematic differences between referral patterns for
cancer patients having a particular kind of employment history and
non-cancer patients with the same employment history."
ISSUE:
Specificity of occupational coding schemes
RESPONSE:
The detailed coding Dr. Kessler recommends would require the incorpora-
tion of not only the patient's occupation but also his exposure
history. Such information was not available to the investigators
from the computerized file used for analysis. Since the usual
effect of heterogeneous groups is to dilute. any specific effect, it
may be that the group at highest exposure was at even greater risk
than hypothesized by this study.
ISSUE: . .
Only small numbers of patients were involved.
RESPONSE:
Of the 25,1416 patients admitted to RPMI, 13,9149 had cancer; the
co*parable groups without cancer were drawn from the remainder.
Some of the 25,1416 patients were excluded fPom the study since they
bad benign neoplasms or did not fit into the selected occupations for
study (see Item 6). At the time of this study, the RPMI data was
unique. If significant results are found based on 97 cosmetologists,
then a larger study might be expected to show even more significant
results.
ISSUE:
Choice of "control" occupations was questionable.
RESPONSE:
Clerical controls were chosen because they were expected to be
relatively free from exposure to carcinogens. Even if the clerical
patients have some exposure to carcinogens, it seens unlikely that
they would be exposed to the same agents as the occupational group
oLinterest. Besides, the effect of some unknown hazard to clerks
would be expected to weaken any difference in cancer experience
between clerks and cosmetologists.
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81
ISSUE:
NIOSH Study was influenc~ed by previous speculations
RESPONSE:
Surely no one study can meet all the qualifications specified to
contrbl all confounding factors in the study *ithout an exceptional
amount of time or cost invested. It is common to refer to other
studies w~4ch both support or contradict data. It is essential to
consider all possible evidence when interpreting data from a single
epidemiologic study.
We have written the Boswel]. Park staff to request their responses to
the following points, since they have the original data available to
them:
a. questionnaire design and administration.
b. Descriptive data on numbers of controls, and demographic
details.
c. Selection and coding of occupations.
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82
`RESPONSE TO DR. FEINSTEIN'S CO1~1ENTS ON ROSWELL PARK STUDY
ISSUE:
Exposure to Hair Dyes
RESPONSE:
Nowhere does the Roswell Park Study state that there was any suspected
etiologic agent. The purpose of this study was to generate, not
to test, hypotheses. Inclusion of heterogeneous groups could be
expected to mask an etiologic agent in one of the groups. Thus, the
appropriate reaction to these results is to try to sharpen the
hypothesis in further studies aimed at possible etiologic agents
which, we agree, would include hair dyes.
ISSUE:
Risk and "Dose" of Exposure
RESPONSE:
No data were available in this study which would allow computation
of dose-response curves. To our knowledge, none of the other
epidemiologic studies had such information either. In general there
is a lack of industrial hygiene sampling results to assess the dose
received by a cosmetologist. NIO~H has requested such information
from Clairol (see letter to Mr. Connor Pay of January 25, l9T8).
ISSUE:
Capricious Statistics
RESPONSE:
The authors address this point in the text. In hypothesis generating
surveillance studies, the established convention is to allow the
overall alpha level to rise in order to hold down the beta risk.
In epidemiologic terms the approach used sacrifices "specificity"
in order to allow for greater "sensitivity", since these are two types
of risks involved which must be accounted for. The "decision-making"
that NIOSH does is to recommend criteria fQr standards. No regulatory
measures are taken by our agency. The difficult decision involves
when and what information should be disseminated.
ISSUE:
Confidence Intervals
RESPONSE:
Dr. Feinstein has used formula 5.19 from Fleiss' book which is
appropriate for "gauging the pre~ision of the estimated odds ratio;
but not in testing its significance" (Fleiss p. 1~6). The more
appropriate formula from Fleiss for estimating the confidence interval
when the odds ratio is used as an estimate of relative risk involves
formulas 5.20 and 5.33. If, for example, one uses these formulas for
cancer of the ovary, one finds that, contrary to Dr. Feinstein's
computations, the confidence ir~terval runs from l.~42 to 6.29, which
implies a statistically significant association between employment as
a cosmetologist and ovarian, cancer. We have rechecked the calculations
PAGENO="0089"
83
in question and find them to be correctly reported according t.O the
stated methodology.
The contractor chose a procedure for estimating the relative risk which
adjusted for age, something Dr. Feinstein's calculations did not do.
The formula used by the contractor was applied consistently throughout
all calculations which meant that there was no a priori reason to
expect cosmetologists to show significant results.
ISSUE:
The Assembled Group
RESPONSE:
First of all Dr. Feinstein's letter has a typographical error.
In line 6, the number "37" should be "97'~~ Second, he misses the
point that if positive results are detected in such a small group,
then it may indicate a serious problem in the larger population of
all cosmetologists.
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84
~RESPONSE TO DR. FEII'TSTEIN'S COMMENTS ON SSA DISABILITY STUDY
Preliminary Draft - Occupational Characteristics for Disabled Female
Worker~: A Descriptive Study.
This study has not yet been completed or released as a final report by
NIOSH. Preliminary results of the study were discussed in a ten-minute
presentation before the Occupational Health and Safety Section of the
American Public Health Association (APHA). A copy of the APHA presentation
was released to Clairol, the Cosmetic, Toiletry and Fragrance Association,
and others requesting these data. The intent of the APHA presentation was
to demonstrate a technique used in surveillance to identify ocoupational
groups which may be experiencing highe~ rates of disease so that further
in-depth studies of those groups might be carried out. It was stated in
the APHA presentation that only selected disease categories or occupational
groups would be discussed, but that a final report would include more
categories and groups. The final report is scheduled to be completed in
June 1978.
The preliminary presentation examines 23 selected occupational groups
categorized according to the Dictionary of Occupational Titles, 3rd edition
and included codes 330-339 (defined in the study as cosmetology). One
criticism was that the category grouping was too broad to address
cosmetologists and hairdressers alone. Since this was a preliminary
finding, further analyses will be made in more detail which are specific to
code 33»=, hairdressers and cosmetologists. We might add that more than 90
percent of the broad group studied (330-339) were coded as 332. The coded
occupation refers to a disabled worker's usual occupation. There is also a
classification to distinguish those employed fewer than five years from all
others. All of these variables will be discussed in the final report.
Our use of the preliminary results on disabled female workers classified in
the broad category of cosmetology for the bulletin was to point out
additional reason for concern since it is believed that hairdressers and
cosmetologists comprise the largest portion of workers with potential
exposure to 2,~-diarninoaniso1e. The preliminary findings referred to the
selected disabling conditions as defined in the International Classifi-
cation of Diseases (Adapted) for an estimated 5,861 disabled female workers
within the broad category of cosmetology. This estimate was made from a
sample of approximately 700 cosmetologists and was derived on a probability
basis from all female disability awards during the period 1969-1972, The
sample is considered representative of the overall national total, while
most of the other studies are not as readily extrapolated.
The Social Security Disability data did show a number of elevated
proportional morbidity ratios (PMbR's) for specific primary malignant
neoplasms. Other occupational groups studied showed elevated PMbR's which
will also be considered for possible further study. However, no other
PAGENO="0091"
85 -
`~occupe~tional group showed more elevated PMbE's for the selected primary
malignant neoplasms than the occupational group, cosmetology.
Comments made on the ten minute APEA presentation of the study (by Dr. A.
Feinste~n) should be viewed as premature. The final report of the study
will include presentation of methodology, complete results with detailed
tables, and discussion of occupations, disabling conditions, and the nature
of the data received from the SSA.
Before the disability study is published., NIOSH will subject the study to
scientific and technical review. This review will include three persons
outside of NIOSH (two from academia). We would also welcome comments and
criticism from pther interested persons during the review process.
PAGENO="0092"
DEPARTMENT OF HEALTH EDUCATION AND WELFARE
PUBLIC HEALTH SERVICE
CEPATER FOR OISRASR CONTROL
January 25, 1978
NATIONAL INSTITUTE FOR 0CCUPAT~ONUL S ETTANDITSU
RO$RRT A. TAFT LARORATORIES
Mr.* Conner N. Pay . . -
Vice President for Corporate Affairs . .
Clairol . ..: .. .
345 Park Avenue . .. . -
New Pork, New York 10022 . .
Dear Mr. Pay: . . ...
This letter is in response to your letter dated January 17, 1978. With
regard to the Social Security Data, . we think it will be possible to
focus our analysis on the specific subcategory of cosmetologists and
hairdressers (DOT code 332). On the matter of the Roswell Park Study,
we are consulting the contractor to determine the poásibility of
reanalyzing this data. -
Your.last sentence, expressing an interest in the degree to which
cosmetologists are exposed to hair coloring, raises an important issue.
I would have thought that your industry would already have such informa.~
tion as part of your responsibility for assuring the safety of the
products you sell. Surely you must have access to industrial hygiene
and epidemiologic surveys of beauty shops as well as your own
manufacturing facilities.
I suggest that you contact the appropriate medical and/or industrial
hygiene staff in your company (or industry) to provide an answer to the
type and quantity of hazardous exposures in the formulating, manufactur~
lug and application of hair collorings as well as other related products.
If you could provtde NIOSH with copies of available reports, we cou~.d
try to. incorporate the information into our analysis. Alternatively,
we may be able to do a more rigorous epidemiologic study by utilizing
information from payroll records, pension files, work history files and.
death certificates from an appropriate manufacturing facility.
Please let me know what sources of information you are. able to find.
Because of the extensive use of hair dyes in our society, there is a
critical need for a more in.depth evaluation of the health and
86
i.~.
PAGENO="0093"
87
Page 2 Mr. Conner M. Pay, 1/25/78
environment of workers in the industry who would seem to be at highest
exposure to Suspected hazards. We look forward to your continued
cooperation in this important matter.
* * * * Sincerely yours,
Robert Spirtas, Dr. P.R.
chief, Illness Effects Section
Surveillance Branch
Division o~ Surveillance, Bazard*
* * Evaluations, and yield Studiëè"
PAGENO="0094"
88
Mr. WUNDER. Thank you, Mr. Chairman. I have no further
questions.
Mr~ Moss. Additionally the staff will be instructed to have a similar
evaluation made of the studies of Clairol and of the Institute, that is,
the studies which have been submitted to this cOmmittee in order that
we mt~y have an independent evaluation of those studies as well as of
the NIOSH studies [see p. 344].
Mr. Moss. Are there any other further questions?
If not, the committee wants to thank you two gentlemen for your
apj~earance.
The committee will now stand adjourned until next Thursday
morning at 10 o'clock when we will meet in room 2322.
[Whereupon at 3:30 p.m., the committee adlourned to reconvene
on Thursday, January 26, 1978, in room 2322 Rayburn House Office
Building.]
PAGENO="0095"
CANCER-CAUSIN~ CHEMICALS
Safety of Cosmetics and Hair Dyes
THURSDAY,' J~ANUARY 26, :1978
HousE oi~ REPRESENTAnVES,
SuBCO1~MITTEE ON OVERSIGHT. AND INVESTIGATIONS,
COMMIrFEE ON INTERSTATE AND FOREIGN COMMEÜCE,
Wa~sMngto%, D.C.
The subcommittee met pursuant to notice, at 10 a m , in room 2322,
Rayburn house Office Building, Hon. John E. Moss (chairman)
presiding.
Mr. Moss. The committee `will be in order.
Today we begin the second day of hearings on the war on cancer.
We will focus our attention on the safety of hair dyes and other cos-
metic products.
Specifically, the Cosmetic, Toiletry, and Fragrance Association-.
CTFA-has issued statements that scientific evidence now exists to
confirm the safety of cosmetic products. We hope to explore their
contentions in depth.
On Monday, this subcommittee was informed by the National
Cancer Institute that at least six hair dye ingredients have been shown
to be carcinogenic in animals. Two of these ingredients are benzidine
derivatives, a known human carcinogen. Staff further informs me that
at least five of these ingredients can now be found in hair dye prod.-
ucts on shelves throughout the Nation.
We expect to hear information at these hearings that carcinogens
may not only be in hair dyes,~ but in other cosmetic products. Nitro-
samines, a class of potent carcinogens, have been found in significant
`concentrations in numerous consumer products We intend to find
out how extensive `this danger is to humans.
We also intend to determine the steps that industry has taken to
remove potentially dangerous ingredients from its products. Since
the Food and Drug Administration.'has limited powers to force removal
of ingredients .from cosmetic products, the public may have no re-
course but to stop using such products, altogether or continue to use
them iand face an unnecessary risk.
(89)
PAGENO="0096"
90
Questions we hope to have answered today include: -
Has the hair dye industry taken steps to remove carcinogenic
ingredients from its products.
Should the hair dye exemption in the Food, Drug, and Cosmetic
Act be removed?
Do nitrosamines in cosmetics pose a potential hazard?
Has the cosmetic industry conducted proper tests to assure the
safety of cosmetic products?
Obviously, the lives of millions of Americans will be affected by
these answers.
I would like to welcome the representatives from the Cosmetic,
Toiletry, and Fragrance Association, the Environmental Defense
Fund, and Dr. David Fine to address these and other questions posed
by the subcommittee.
At this time I am pleased to recognize Dr. James H. Merritt, presi-~
dent of the Cosmetic, Toiletry, and Fragrance Association. He is ac-
companied by Norman F. Estrin, vice president for science; John F.
Corbett, chairman of the Hair Dye Technical Committee; and Peter
Barton Hutt, counsel.
Gentlemen, will you all be testifying?
Mr. MERRITT. Yes; we will.
Mr. Moss. Will you stand and be sworn in? /
Do you solemnly swear that the testimony you are about to give
this subcommittee is the truth, the whole truth, and nothing but the
truth, so help you God?
[Chorus of "I do's" by witnesses.]
Mr. Moss. Identify yourself to the reporter for the hearing record,
please.
Dr. CORBETT. Dr. Corbett.
Dr. ESTRIN. Dr. Estrin.
Mr. MERRITT. Mr. Merritt.
Mr. HUTT. Mr. Hutt.
Mr. Moss. Mr. Merritt, you may proceed.
TESTIMONY OP NAMES H. MERRITT, PRESIDENT, TEE COSMETIC,',
TOILETRY, AND FRAGRANCE ASSOCIATION, INC., ACCOMPANIED
BY NORMAN F, ESTRIN, FE. D., VICE PRESIDENT, SCIENCE; bEN
P. C~RBETT, PH. D., CHAIRMAN, HAIR DYE TECHNICAL COMMIT-
TEE; AND PETER BARTON HUTT, COUNSEL
Mr. MERRITT. Mr. Chairman and members of the subcommittee,
my name is James H. Merritt. I am president of the Cosmetic, Toil-
etry, and Fragrance Association-CTFA-the national trade associ-
ation of the cosmetic industry.
I am accompanied today by three others in order that we might
provide you accurate and authoritative responses to questions you
raise.
Those with me are: Dr. JohnCorbe1~t, chairman, CTFA Hair Dye
Technical Committee and vice president, technology, Clairol, Inc.;
Dr. Norman F. Estrin, vice president, CTFA; and Peter Barton Hutt,
CTFA counsel and partner, Covington and Burling.
CTFA represents approximately 225 manufacturers and distrib-
utors of cosmetic products, and about 200 manufacturers and dis-
PAGENO="0097"
91
tributors of cosmetic product ingredients and supplies. CTFA mem-
bers. manufacture approximately 90 percent of the volume of cos-
metic products distributed in the United States, The cosmetic industry
accounts for about $9 billion of retail sales in the United States yearly
and provides the livelihood for literally millions of people in this
country.
CTFA is appearing today, at your request. To summarize, we
believe that:
Cosmetic products are safe, and are among the safest products of
any kind consumers can buy.
FDA has adequate legal authority to take appropriate regulatory
action to protect the public against unsafe cosmetics.
The cosmetic industry has initiated many programs to meet its
obligation to the public to assure the safety of the products it markets.
We are aware of no reliable evidence that cosmetics contribute to
human cancer. We believe that Dr. Upton's statements, made in his
testimony on Monday, fully support our position.
Cosmetics have been used for centuries. We find evidence of them
in every recorded civilization. For thousands of years, men and women
have created cosmetic products, from whatever raw materials were
available, to help satisfy their fundamental human need for self-
assurance and self-esteem. Modern industry has simply improved
upon these . traditional product forms by making them far purer,
safer, and more attractive than ever before.
* Cosmetics are manufactured and distributed by companies which
range from very small to very large. Cosmetic products are marketed
through every form of retail channel, including retail stores, mail
order, and door-to-door salespersons.
Cosmetics cover a broad range of products, from perfume and lip-
stick to deodorants, toothpaste, and shaving cream. Because many
cosmetic products are oriented toward the fashion industry, they are,
like fashion, subject to very rapid change. These product changes
utilize well-recognized ingredients that have been used in hundreds
of cosmetic products for years, and thus represent no significant change
in the safety of the product.
Cosmetic products have an enviable safety record. In September
1973, the panel on chemicals and~ health of the President's Science
Advisory Committee issued a report published by the National Science
Foundation which concluded with respect to cosmetics:
From what may be judged human experience, the incidence of injury is small.
In the total pattern of environmental risks, those from cosmetics are both in-
frequent and slight.
While there are no formal pretesting or preclearance requirements for cos-
metics, the total effect of individual and informal review-usually private rather
than governmental-together with the innocuousness of most materials used, has
made the injury rate fairly low by comparison with other widely prevalent sources
of hazard.
It seems likely, though solid information is lacking, that the actual injury rate
from cosmetics has declined, while the complaint rate has increased as a result
of greater óonsumer awareness of the Food and Drug Administration as a regula-
tory agency, and of the existence of legal and insurance remedies.
Company records show that reactions to cosmetics are rarely serious
and are almost invariably transient and reversible. We are unaware
that any case of cancer has ever been shown to have been caused by
any cosmetic.
24-600 0 - 78 - 7
PAGENO="0098"
92
Cosmetics were~ first included under Federal regulatory controls in
the Federal Food, Drug, and Cosmetic Act of 1938. The legislative
history of that act does not reveal, however, any general allegation
that cosmetics as a whole had produced substantial consumer harm.
It was recognized that some cosmetic products-like food, drugs,
and all other consumer items-do on occasion produce al1er~ic re-
actions. The legislative history clearly reveals Congress did not intend
that cosmetic products or other consumer products be removed from
the market because of these isolated reactions. Congress concluded
that the benefits of cosmetics outweighed the risks caused by their use.
The cosmetic provisions of the 1938 Act contain a broad array of
legal sanctiOns under which FDA can protect consumers against
potential harm from cosmetics. CTFA believes that these provisions
are adequate, and that no additional legislation is necessary to protect
the public.
Regulatory action taken under the present law during the past few
years readily demonstrates the breadth of present FDA authority
over cosmetics. CTFA has not on any occasion instituted legal action
to challenge the authority of FDA to undertake this typO of regulatory
action. We have, on occasion, contested the factual basis for proposed
action, but not the legal authority. Where there is an adequate factual
basis for informing consumers about possible product hazards, for
example, we have not opposed the action taken.
A very brief review of some of the FDA regulations promulgated in
the past few years will demonstrate that the agency does not lack the
legal authority necessary to impose regulatory requirements where
they are warranted.
Under the Color Additive Amendments of 1960, FDA has enormous
authority to require safety testing for all color ingredients. CTFA is
now sponsoring carcinogenicity retesting for 10 color additives, as
requfred by FDA.
The FDA regulation requiring ingredient labeling for cosmetics is
effective. The regulation requires that all retail cosmetic packaging
list the ingredients in descending order of predominance with the
exception of flavor and fragrance. It is more informative than food
ingredient labeling because it requires specific designation of color
ingredients, and is far more informative than drug ingredient labeling
which requires declaration only of active ingredients.
Any cosmetic which has not been adequately substantiated for safety
prior to marketing is required by an FDA regulation to bear the
warning statement that "the safety of this product has not been
determined."
In addition to these particular regulations, FDA has taken action
under its general authority, to prevent the marketing of adulterated
and misbranded products both through the requirement of recalls and
by direct legal action in the courts. In short, there is no evidence that
any product which has been shown to produce substantial harm to
humans remains on the market today through lack of FDA regulatory
authority. , . ,
CTFA strongly supports the concept of safety substantiation, firmly
beliOving that it is the obligation of every manufacturer and dis-
tributor not to market any cosmetic whhth has not been substantiated
for safety. CTFA. has not challenged the legal authority of FDA to
PAGENO="0099"
93
promulgate its regulation requiring safety substantiation, and has
over the years established many programs designed to help industry
meet its obligation to the public even before it became a legal require-
ment. A brief summary of some of the more important CTFA pro-
grams is as follows.
CTFA inaugurated its scientific program 30 years ago with the
establishment of analytical standards for ingredients commonly used
in cosmetics. In the past 10 years it has formed scientific commit-
tees of qualified experts to analyze and resolve scientific questions
dealing with microbiology, pharmacology and toxicology, quality
assurance, color safety, hair coloring, ingredient nomenclature, and a
wide variety of other subjects. CTFA regularly develops and dissemi-
nates standards for raw material specifications, testing methods, and
ingredient descriptions, as well as technical guidelines to help insure
the quality and safety of finished products.
OTFA initiated and submitted three major petitions to FDA, on
the basis of which FDA has promulgated regulations governing volun-
tary registration of cosmetic product manufacturing plants, filing of
cosmetic product formulas, and filing of cosmetic product experience
reports. The following statistics reflect voluntary industry participa-
tion in these three programs as of September 30, 1977. About 900
cosmetic plants have been registered with FDA, representing about
85 percent of the volume of cosmetics sold in the United States.
Some 23,500 cosmetic formulas have been submitted to FDA, repre-
senting about 80 percent of the volume of cosmetics sold in the United
States. About 125 companies were participating in the product
experience reporting program, representing about 50 percent of the
volume of cosmetics sold in the United States. We believe that this
voluntary program represents a major source of important informa-
tion to FDA and to the public that would otherwise not be available,
on which valid r~gulatory programs can be based.
CTFA has submitted to FDA a petition requesting that FDA
promulgate regulations governing goo4 manufacturin~ practices in
making cosmetic products. We hope that FDA will publish a proposed
regulation in the near future.
CTFA has recently undertaken a major program to review the
safety of cosmetic ingredients. All available published and unpub-
lished data on individual ingredients will be compiled and submitted
for review by an independent expert panel of eminent scientists. The
expert panel members have been required to meet the same strict
conflict.of-interest standards as are applied to members of Federal
Government advisory committees. The review process is modeled
directly after current FDA safety review programs, and includes a
consumer liaison selected by consumer organizations, an industry
liaison, and an FDA contact person. I am submitting for the record,
the procedures that govern this review. We believe that it represents
the most comprehensive and open safety review ever undertaken by
private industry..
Mr. Moss. Without objection, it will be inserted in the record at
* this point following your statement [see p. 97].
Mr. MERRITT. In response to the recent discovery reports that nitro-
samiiies may be formed as contaminants in cosmetic ingredients
or cosmetic products, OTFA immediately organized a program to
PAGENO="0100"
94
refine and improve the detection methodology and to analyze common
cosmetic ingredients to determine the source of any nitrosamine con-
tamination. CTFA recognizes that nitrosamines serve no function
in cosmetics and is committed to eliminating them or reducing them to
the lowest level feasible. Nitrosamines do, of course, occur naturally
in the human body and throughout our environment, and are found in
air, water, and many other categories of consumer products.
CTFA has carefully reviewed the recent allegation that certain hair
dye ingredients are carcinogenic in test animals. On the basis of all of
the available animal tests, and considering the many flaws in the
National Cancer Institute test, we do not believe that allegation is
scientifically supportable.
We are' concerned `that NIOSH has chosen to rely on two epidemio-
logical studies that have been severely criticized and has chosen to
ignore the two definitive epidemiology studies in the field-the Amer-
ican Cancer Society's study which covered 5,000 actual hairdressers
and matched groups of 5,000 nonhairdressers, and the NCI-funded
Yale University study which covered 12,000 hairdressers and, 12,000
school teachers. Both studies showed no link between hair dyes and
cancer.
For that reason, we believe that the totality of the available scienti-
fic information does not support a warning to consumers. Certainly
if any information is provided to consumers it should be presented in a
complete and balanced way so that a fully informed choice can be
made, and not by a cryptic warning that is designed more to scare
consumers than to help them make a reasoned decision.
The concern about hair dyes and the exemption for hair dyes in
Section 601 (a) of the Act has been blown out of all proportion. Cer-
tainly, before any action is taken by Congress to reconsider the statu-
tory provisions for hair dyes the matter should be thoroughly re-
viewed by an independent scientific body like the National Academy
of Sciences.
We listened very carefully to the testimony given Monday by the
distinguished Director of the National Cancer Institute, Dr. Upton.
We are in virtually complete agreement with the statements he made.
Let me summarize his major points:
One, the NCI bioassay program was not intended to, and does not,
provide a definitive evaluation of the carcinogenic potential of hair
dye ingredients in humans. It was intended as a screening test, and
therefore used very high dose feeding levels. If a substance is not shown
to be carcinogenic in the animal bioassay there need be no further
concern about it; if it is shown to be carcinogenic in the animal bio-
assay, it should be subjected to further testing and analysis in order
to determine whether there is any human risk.
Two, there is substantial scientific controversy, among qualiflçd
experts, with respect to many important issues relating to animal
testing for carcinogenicity: for example, wliiether high-dose levels
overwhelm a test animal's detoxification defenses and therefore are
not appropriate; whether animal data are reliable in predicting human
risk; and whether there is a threshhold below which a proven car-
cinogen will nonetheless have no effect. As to these scientific issues,
the uncertainties are overwhelming.
PAGENO="0101"
95
Three, the incidence of cancer in women in the United States is
decreasing. If cancer of the lung-which NOT attributes primarily
to smoking-is disregarded, this decrease is substantial.
Four, the NOT bioassay studies are an insufficient scientific basis
to justify banning any hair dye found to be carcinogenic in test ani-
mals. The proper response to the possibility of risk from any con-
sumer product is a "societal issue," not a scientific issue. What is
prudent action for one consumer is not acceptable to all consumers.
Consumers should have a right to determine, for themselves, the
risks that they are willing' to accept. Banning any hair dye ingredient
is going too far at this time.
We join in Chairman Moss' concern about NOT's inability to re-
lease the final reports on substances in the NOT bioassay testing pro-
gram on an expeditious and consistent basis. All of the reports on
hair dye substances should have been completed aTid released at the
same time. This would then have permitted a more rational basis for
action by both industry and FDA, the regulatory agency that must
deal with this issue. One cannot consider reformulation of hair dyes,
or the availability of alterntive ingredients, by approaching the matter
on a piecemeal basis.
CTFA fully supports the concept of the Interagency Regulatory
Liaison Group. We will soon be recommending that the concept of
classifying substances according to potential carcinogenic risk pro-
posed by the Occupational Safety and Health Administration last
October be expanded and applied to all of the regulatory agencies
participating in the IRLG. A consistent and coordinated govern-
mental policy in this area is essential to Government, consumer,
labor, and industry interests alike.
CTFA recognizes that, as science progresses, more and more ques-
tions will be raised about all consumer products, including cosmetics.
We feel that unwarranted regulator action will be taken on the basis
of hypothetical concerns, without careful assessment of the actual
risks involved and without adequate recognition of the benefits that
the American public obtains from cosmetic products. To the vast
majority of consumers, the contributions of cosmetics to self-assurance
and self-esteem are as important as the nutritional and medical bene-
fits of foods and drugs.
We are in complete agreement with the suggestion made by Mr.
GOre on Monday that the American people should be given a chart
showing the various possible sources of cancer and the relative risks
involved from each source. We would, indeed, expand this suggestion
to show the various other sources of hazard-such as driving in auto-
mobiles and flying in airplanes-and the relative risk that each of
those entails.
This would, for the first time, put the issue of risk in perspective.
Consumers would have a basis for making fully informed choices.
The cosmetic industry is confident that, faced with this risk informa-
tion, consumers would be reassured about the relative safety of its
products.
We must all recognize that we do not live in a risk-free society. The
risks that we all assumed in flying to Washington or driving to this
hearmg are, in our opinion, far more certain than any hypothetical
PAGENO="0102"
96
risk raised by cosmetic products. Indeed, the risks posed by cosmetics
can be calculated to be far smaller than the risks associated with many
other consumer products.
We are convinced that any fair evaluation of all the available
evidence shows that cosmetics do not present a substantial risk of
harm to consumers. We believe taht both Congress and the general
public recognize the value of cosmetic products and that unwarranted
attempts at overregulation would be rejected by the Congress and the
American people.
Thank you, Mr. Chairman. We will attempt and endeavor to answer
any questions you or any members of the subcommittee have or
members of your staff have.
[Testimony resumes on p. 121]
[The review procedure referred to follows:]
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* Cosmetic Ingredient Review
1133 Fifteenth Street, NW., Suite 1275, WashIngton, D.C. 20005 * 202~-331-0651
COSMETIC INGREDIENT REVIEW
* PROCEDURES
REVISED
(Includes amendments approved by CIR Steering Committee
and C~FA Board of Directors as of December 20, 1976)
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COSMETIC INGREDIENT REVIEW PROCEDURES
TABLE OF CONTENTS
Part A - General 1
Sec. 1 - ~Definitions 1
Sec. 2 - Purpose of the Cosmetic Ingredient Review 2
Sec. 3 - Interpretation and Amendment of Procedures 2
Part B - The Cosmetic Ingredient Review Steering Committee and Staff . . . 2
Sec. 10 - Organization of the Cosmetic Ingredient Review 2
Sec. 11 - Separation and Independence of the Cosmetic Ingredient
Review Staff from the CTFA Staff 3
Sec. 12 - Director 3
Sec. 13 - Administrator . 3
Sec. 14 - Scientific Coordinator 4
Part C - The Cosmetic Ingredient Review Expert Panel and Liaison
Representatives 4
Sec. 20 - Members of the Expert Panel and Liaison Representatives . . 4
Sec. 21 - Nominations and Selection of Members of the Expert Panel. . 4
Sec. 22 - Selection of Liaison Representatives to the Expert Panel. . 5
Sec. 23 - Rights and Responsibilities of Liaison Representatives
to the Expert Panel 5
Sec. 24 - Compensation of Expert Panel Members and Liaison
Representatives 6
Sec. 25 - Chairman of the Expert Panel 7
Sec. 26 - Ex Parte Contacts with the Expert Panel 7
Sec. 27 - Compilation of Background Materials for Members of the
Expert Panel and Liaison Representatives 7
Part D - The Cosmetic Ingredient Review Procedures 7
Sec. 30 - Compilation of Safety Data and Information and Review
by the Expert Panel 7
Sec. 31 - Meetings of the Expert Panel 12
Sec. 32 - Additional Rules for the Expert Panel 13
Sec. 33 - Consultation by the Expert Panel with Other Persons . . . . 13
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Sec. 34 - Portions of Expert Panel Meetings 13
Sec. 35 - Notice of Public Hearing and fleeting of the Expert Panel. . 14
Sec. 36 - Determination to Close Portions of Expert Panel Meetings. . 14
Sec. 37 - Administrative Remedies 15
Sec. 38 - Written Submissions to the Expert Panel 15
Sec. 39 - Conduct of a Public Hearing Before the Expert Panel . . . . 15
Sec. 40 - Minutes and Reports of Expert Panel Meetings 17
Sec. 41 - Transcripts of Expert Panel Meetings 17
Sec. 42 - Expert Panel Determinations 18
Sec. 43 - Tentative Report of the Expert Panel 18
Sec. 44 Final Report of the Expert Panel 18
Sec. 45 - Amendment of a Final Report 18
Part E - Public Notice and Availability of Records 19
Se~c. 50 - Public Notice 19
Sec. 51 - Availability of Records for Public Disclosure . 19
Sec. 52 - Public Documents Room 20
Sec. 53 - Public Inq~uiries and Requests for the Cosmetic
Ingredient Review Records 21
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COSMETIC INGREDIENT REVIEW
PROCEDURES
Part A -- General
Section 1. Definitions.
(a) "Act". means the. Federal Food, Drug, and Cosmetic Act.
(b) "Cosmetic' means (1) articles intended to be rubbed, poured, sprinkled,
or sprayed on, introduced into, or otherwise applied to the human body or any part
thereof for cleansing, beautifying, promoting attractiveness, or altering the
appearance, and (2) articles intended for use as a component of any such articles;
except that it shall not include soap.
(C) "Cosmetic ingredient" means any chemical substance used as a component
ib the manufacture of a cosmetic product, but shall not include a proprietary
mixture.
(d) "Cosmetic product" means a finished cosmetic the manufacture of which
has been completed.
(e) "Commercial distribution" of a cosmetic product means annual gross
sales J4~ excess of $1,000 for the product.
(f) "Chemical description" means a concise definition of the chemical
composition using standard chemical nomenclature so that the chemical structure
or structures of the components of the ingredient would be clear to a practicing
chemist, When the composition cannot be described chemically, the substance shall
be described in terms of its source and processing. -
(g) "Flavor" means any natural or synthetic substance or substances used
solely to impart a taste to a cosmetic product.
(h) `Fragrance' means any natural or synthetic substance or substances used
solely to impart an odor to a cosmetic product.
(i) "Cosmetic Ingredient Review" means the Cosmetic Ingredient Review pro-
gram conducted pursuant'to these procedures.
(j) "CTFA' means The Cosmetic, Toiletry and Fragrance Association, Inc.
(k) "Director' means the Director of the Cosmetic Ingredient Review, who
shall have the authority and responsibilities established in Section 12 of these
procedures.
(1) "Administrator' means the Administrator of the Cosmetic Ingredient
Review, who shall have the authority and responsibilities established in Se~tion
13 of these procedures.
(m) `Scientific Coordinator' means the Scientific Coordinator of the
Cosmetic Ingredient Review, who shall also be the Executive Secretary of the
Expert Panel, who shall have the authority and responsibilities established in
Section 14 of these procedures.
(n) `Expert Panel" means the Cosmetic Ingredient Review Expert Panel, which
shall be established and shall have the authority and responsibilities established
in Part C of these procedures and shall conduct the Cosmetic Ingredient Review
program in accordance with the procedures established in Part D of these proce-
dures.
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(0) "Executive Secretary" means the Executive Secretary of the Expert Panel,
who shall be the Scientific Coordinator and shall have the authority and responsi-
bilities established in Section 14 of these procedures.
(p) "Safe" or "safety" means ho evidence in the available information that
demonstrates or suggests reasonable grounds to suspect a hazard to the public
under the conditions of use that are now current or that might reasonably be
expected in the future, ~ a low incidence of minor adverse reactions (as shown
in animal or human testing or product experience). Such information includes, but
is not limited, to, the chemical structure of the ingredient, published and
unpublished tests on the ingredient and products containing the ingredient, signi-
ficant human experience on products containing the ingredient during marketing,
and information on similar o.r related substances. A lack of information about an
ingredient shall not be sufficient to justify a determination of safety.
(q) "Conditions of use" for an ingredient or product include (1) the amount
of an ingredient used in a product, (2) the intended and reasonably foreseeable
areas of use (fj~, use that is subject to ingestion or inhalation or contact with
mucous membranes or is in the area of the eye), and (3) directions for use and
against misuse in labeling.
Section 2. Purpose of the Cosmetic ingredient Review.
The purpose of the Cosmetic Ingredient Review is to determine those cosmetic'
ingredients for which there is a reasonable certainty in the judgment of competent
scientists that the ingredient is safe under its conditions of use.
~ption 3. interpretation and Amendment of Procedures.
(a) if any dispute arises as to the proper interpretation or application of
these procedures, a majority vote of the Steering Committee shall be final and
binding with respect to such matter.
(b) These procedures may be amended by a two-thirds vote of the Steering
Committee, .Vith the approval of the CTPA Board of Directors. The Administrator
shall give public notice of any amendment of these procedures.
Part B -- The Cosmetic Ingredient Review Steering
Committee and Staff
Section 10. Organization, of, the Cosmetic Ingredient Review.
(a) General policy and dIrection for the Cosmetic ingredient ~eview shall
be given by a Steering Committee., A quorum of the steering Committee shall
consist of three members. Any matter before the Steering Committee shall be
decided by a majority vote of the mmmbers present at the time except where other-
wise specifically provided in these procedures. T)~e steering Committee shall
consist of the following members:
(1) The President of CTPA, who shall serve as the Chairman of the
Steering Committee.
(2) A dermatologist, who shall represent the American Academy of
Dermatology.
(~) A toxicologist, who shall represent the Society of Toxicology.
(4) The Chairman of the CTFA Scientific Adivso'ry Committee.
(5) The CTFA Vice President for Science.
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(b) The Cosmetic Ingredient Review staff shall consist of a Director, who
shall report to the Cosmetic Ingredient Review Steering Committee, and the
Administrator and the Scientific Coordinator, who shall report to the Director.
The Director, Administrator, and Scientific Coordinator may in turn utilize such
other personnel as is necessary and appropriate to carry out their authority and
responsibilities established in Sections 12-14 of these procedures.
Section 11. Separation and Independence of the Cosmetic Ingredient Review Staff
from the CTFA Staff.
(a) The Cosmetic Ingredient Review staff shall be employees of or consul-
tants to CTFA but shall be separate and independent from the CTFA staff. No
person on the Cosmetic Ingredient Review staff may also serve on the CTFA staff.
The Cosmetic Ingredient Review staff may obtain supplies and services through the
central facilities of CTFA. Contact between the Cosmetic Ingredient Review staff
and the CTFA staff shall be kept to the minimum n~ecessary to conduct the affairs
of the Cosmetic Ingredient Review efficiently and effectively. CTFA staff shall
be treated by the Cosmetic Ingredient Review staff the same as any other member
of the public ~ all CTFA staff shall sign the visitors log when visiting the
Cosmetic Ingredient Review offices).
(b) The Cosmetic Ingredient Review staff shall follow all personnel
policies and procedures established in the CTFA Procedures Manual, except that the
Director shall be responsible for all required approvals within the authority
granted to him under Section 12 of these procedures.
Section 12. Director.
(a) The Director shall be appointed by the CTFA President, with the ap-
proval of the Chairman of the CTFA Board of Directors and the Chairman of the
CTFA Scientific Advisory Committee.
(b) The Director shall hire and direct the activities of the Cosmetic
Ingredient Review staff in order to implement these procedures effectively and
efficiently. The Director shall report to and be subject to the direction and
control of the Steering Committee with respect to policy and budget within the
following limitations:
(1) The CTFA Board of Directors shall determine the budget and per-
sonnel limits for the Cosmetic Ingredient Review.
(2) The Steering Committee shall periodically review all Cosmetic
Ingredient Review expenditures ~ document reproduction, Communications,
accounting, and office space expenditures) to determine that they are within the
budget.
(3) All Cosmetic Ingredient Review contracts and capital expenditures
shall be reviewed and approved by the Steering Committee prior to execution.
(4) All Cosmetic Ingredient Review office supplies shall be obtained
through CTFA central purchasing unless otherwise approved by the Steering Com-
mittee. /
(c) The Administrator or Scientific Coordinator may simultaneously serve
as the Acting Director in the absence of the Director, or as the Director.
Section 13. Administrator:
The Administrator, under the direction of the Director, shall have authority
and responsibility for daily administration of the Cosmetic Ingredient Review
staff and Expert Panel. This shall include receipt of all documents submitted by
any interested person with respect to the Cosmetic Ingredient Review, distribution
of all data and infotmation to the Expert Panel, arranging for all aspects of the
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meetings of the Expert Panel, including public notice thereof~ serving as secre-
tary to the Steering Committee, and all similar administrative functions.
Section 14. scientific Coordinator.
The Scientific Coordinator, under the direction of the Director, shall have
authority and responsibility to perform all of the scientific functions of the
Cosmetic Ingredient Review staff~(including, but not limited to, the information
science function and obtaining all necessary Scientific Literature Reviews) and of
the Expert Panel (including,but not limited to,preparing minutes of all Meetings,
drafting scientific position papers, and otherwise serving as Executive Secretary
to the Expert Panel).
Part C - The Cosmetic Ingredient Review Expert Panel
and Liaison Representatives
Section 20. Members of the Expert Panel and Liaison Representatives.
(a) Members of the Expert Panel shall possess the following qualifications:
(1) Members shall possess expertise relevant to the review of the
safety of cosmetic ingredients. They shall have diverse professional education,
training, and experience so that the Expert Panel will reflect a balanced composi-
tion of sufficient scientific expertise to handle the issues that come before it.
(2) Members shall be required to meet the same conflict of interest
standards as are applicable under Federal law to special government employees.
(3) Liaison representatives shall be selected by the interested
organizations as provided in Section 22 of these procedures. Technical expertise
with the subject matter with which the Expert Panel is involved shall not be a
requirement.
(b) Members appointed to the Expert Panel and liaison representatives shall
continue to serve for the duration of the Expert Panel or until they resign or
are removed from membership for cause by the Steering Committee.
Cc) An Expert Panel member may be removed from membership by the Steering
Committee for good cause. Good cause shall include but not be limited to exces-
sive absenteeism from Expert Panel meetings, a demonstrated bias which interferes
with the ability to render objective advice, or failure to abide by these proce-
dures.
Cd) There shall ordinarily be seven members of the Expert Panel, each mem-
ber having an equal vote. The Expert Panel shall begin to function, and may
continue to function, as long as there are not less than five members.
Section 21. NominatiOns and Selection of Members of the Expert ne].
Ca) The Administrator shall give public notice requesting nominations for
members of the Expert Panel. The notice shall invite the submission of nomina-
tions for members from any interested individual as well as from consumer,
industry, and professional organizations, within 90 days of such notice.
(b) Any interested person may nominate one or more qualified person(s) as a
member of the Expert Panel. Nominations shall include a complete curriculum vitae
of the nominee, and shall state that the nominee is aware of the nomination, is
willing to serve as a member of the Expert Panel, and appears to have no conflict
of interest which would preclude membership on the Expert. Panel.
Cc) Members of t'he Expert Panel shall serve as individuals and not as
representatives of any group or organization which nominated them or with which
they may be affiliated.
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(d) The Steering Committee shall appoint the members of the Expert Panel
from among those who have been nominated. Appointment shall be decided by a
four-fifths vote of all current members of the Steering Committee. Appointment
shall be on the basis of scientific competence, expertise in an area relevant to
the Cosmetic Ingredient Review, balance of scientific disciplines within the
Expert Panel, willingness to devote sufficient time and energy to the review, and
the lack of any disqualifying conflict of interest.
(a) All data and information relating to the nomination and selection of
the members of the Expert Panel shall be maintained by the Administrator in a
confidential file.
(f) Vacancies in the membership of the Expert Panel shall be filled by the
Steering Committee either from prior nominations or in the same way that members
are initially nominated and selected.
Section 22. Selection of Liaison Representatives to the Expert Panel.
(a) The Administrator shall request that each of the following interests
designate a liaison representative to the Expert Panel:
(1) The Food and Drug Administration, in accordance with the provi-
sions of proposed 21 C.F.R. 2.21(d).
(2) Organizations representing consumer interests.
(3) CTFA.
(b) Liaison representatives to the Expert Panel shall be limited to three
persons, one representing each of the listed interests. Those interests may,
however, designate different liaison representatives for purposes of the review of
different categories of cosmetic ingredients or similar considerations. At no
time may there be more than one liaison representative to the Expert Panel from
any one of the interests listed in Section 22(a) of these procedures with respect
to any specific cosmetic ingredient.
(C) Because liaison representatives for government, consumer, and industry
interests have no vote, their selection shall be solely by the interests they
represent and shall be without regard to the conflict of interest principles
for special government employees that are applicable to the members of the Expert
Panel.
(~) Vacancies in the liaison representatives to the Expert Panel shall be
filled in the same way that liaison representatives are initially selected.
Section 23. Rights and Responsibilities of Liaison Representatives to the
Expert Panel.
(a) A liaison representative to the Expert Panel selected to represent and
serve as a liaison with interested individuals, associations, and organizations,
shall haVe the same rights as members of the Expert Panel except that:
(1) A liaison representative shall not vote on any matter before the
Expert Panel.
(2) A liaison representative shall not have access to confidential
data and information that are not availakle for public disclosure pursuant to
Section 51(b), of these procedures. Accordingly, a liaison representative
shall not be present at any portion of an Expert Panel meeting which is closed for
the presentation of confidential data pursuant to Section 34(c) or the discussion
of confidential data pursuant to Sections 34(d) and 36(b) (2) of these procedures
which are prohibited from public disclosure pursuant to Section 51(b) of these
procedures.
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(b) A liaison representative of the Expert Panel is subject to, and shall
abide by, all aspects of these procedures and any rules and regulations adopted by
the Expert Panel pursuant to Section 32 of these procedures.
Cc) It is the responsibility of the liaison representatives to the Expert
Panel to represent the government, consumer, and industry interests in all delib-
erations.
(1) The consumer and industry liaison representative does not repre-
sent any particular organization or group, but rather represents a]). interested
persons within the class which he is selecteâ to represent. Accordingly, any in-
terested person within the class represented by that liaison representative shall
have access to all written statements or oral briefings related to the Expert
Panel prepared by the liaison representative for distribution to any person out-
side the Expert Panel.
(2) Liaison representatives shall review all official Expert Panel
minutes to assure their completeness and accuracy.
(3) The liaison representative shall act as a liaison with and con-
duit between the Expert panel and the interested persons whom he represents, and
shall transmit requests for information from the Expert Panel and relevant data,
information, and views to the Expert Panel. He shall take the initiative in con-
tacting interested persons whom he represents, to seek out relevant data, infor-
mation, and views, and to relate the progress of the Expert Panel.
(4) The industry liaison representative shall represent all members
of the industry, and not any particular association, company, product, or ingredi-
ent. Ii a matter comes before the Expert Panel that directly or indirectly
affects the company which employs the industry liaison representative, he need
not absent himself during the discussion or c~ecline to participate in the dis-
cussion. The industry liaison representative shall not discuss his company's
position as such, but may discuss any matter in general terms. All presentations
and discussions of scientific data and their interpretation on behalf of a com-
pany shall occur in open session, except as provided in Section 34(c) of these
procedures.
(5) A liaison representative to the Expert Panel shall not make any
presentation to the Expert Panel during a hearing conducted by the Expert Panel.
(6) Although a liaison representative is serving in a representative
capacity, he shall exercise restraint in performing his functions and shall not
engage in unseemly advocacy or attempt to exert undue influence over members of
the Expert Panel.
Cc) A liaison representative to the Expert Panel may be removed by the
Steering Committee for failure to comply with the provisions of this section or
the other sections of these procedures. Zn the event of removal of a liaison
representative, the interests which he has represented shall be requested to
select a new liaison representative.
Section ~4. CompensatiOn of Expert ?anel ~embe~.
(a) All members of the Expert Panel and liaison representatives shall
receive a consultant fee of $400 per day and be reimbursed for their travel
expenses and all Other out-of-pocket expenses, unless such compensation and reim-
bursement is waived.
(b) An Expert Panel member or liaison representative notwithstanding his
primary residence, while in attendance at meetings of the Expert Panel, will be
paid whether the meetings are held in his city of residence or elsewhere.
Cc) An Expert Panel member or liaison representative who participates in a
specific assignment for the Expert Panel, at the request of the Cosmetic
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Ingredient Review, will be paid at an hourly rate of $50 when he perfotms his
work at home, place of business, or elsewhere, and at a daily rate when he is
required to travel outside of his commuting area to perform his assignment. An
Expert Panel member or liaison representative will not be paid for time spent on
normal preparatiofi for a meeting of the Expert Panel.
Cd) Salary while in travel status is authorized when an Expert Panel member
or liaison representative has his ordinary pursuits interrupted for the substan-
tial portion of an additional day beyond the day or days on which he performs
services, and as a consequence he sustains a loss in his regular compensation.
This applies on weekends and holidays~ if the Expert Panel member or liaison repre-
sentative suffers a loss in income he would otherwise earn on that day. For travel
purposes, a substantial portion of a day is defined as 50 percent of the working
day, and the traveller will be paid at a daily rate.
Section 25. Chairman of the Expert Panel.
(a) The Steering Committee shall selecit a Temporary Chairman of the Expert
Panel from among the members, who shall serve as the Temporary Chairman for the
initial organizational meetings. Thereafter, the Expert Panel shall determine
its own Chairman from among the members, who may serve on a permanent or on a
rotating basis.
(b) The Expert Panel Chairman shall have the authority to conduct hearings
and meetings, including the authority to adjourn any hearing or meeting whenever
he determines adjournment to be advisable, to discontinue disccnssion of a parti-
cular matter, to conclude the open portion of a meeting in accordance with Section
36 of these procedures, or to take any other action in furtherance of a fair and
expeditious hearing or meeting.
Section 26. Ex Parte Contacts With the Expert Panel.
(a) There shall be no cx parts Oontacts between the members of the Expert
Pat~iel and anyone other than a liaison representative to the Expert Panel or a
member of the Cosmetic Ingredient Review staff with respect to any matter relating
to the Cosmetic Ingredient Review, except that:
(1) The Steering Committee may meet with the Expert Panel or any
members thereof or any liaison representatives to discuss the work of the Expert
Panel.
(2) A member of the Expert Panel may, in his discretion, initiate
discussions with any other scientist for the purpose of obtaining data, infor-
mation, or views with respect to any scientific issue.
(b) If any person initiates an cx parte contact with a member of the Expert
Panel other than as permitted by paragraph (a) of this section, such member shall
refer such person to the Cosmetic Ingredient Review staff for advice on the pro-
cedures for submission of data, information, and views to the Expert Panel.
Section 27. Compilation of Background Materials for Hembers of the Expert Panel
jand Liaison Representatives.
The Administrator shall prepare and provide to Expert Panel members and
liaison representatives a complete compilation of background materials bearing
upon their duties and responsibilities.
Part D -- The Cosmetic Ingredient Review Procedures
Section 30. Compilation of Safety Data and Information and Review by the Expert
- Panel.
(a) The Steering Committee shall develop a tentative priority list(s) for
the systematic review of all cosmetic ingredients presently used in commercially
distributed cosmetic products. This tentative priority list(s) shall be based
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107
upon the frequency of use (i.e., the number of different products in which an
ingredient is used), availakUityof chemical specifications or descriptions,
any known questions about safety, and the availability of sufficient data and
information for the Expert Panel to make an informed scientific judgment on safety.
(1) For those cosmetic ingredients for which no particular priority
can be established, their priority shall be determined by a statistically reliable
randomization.
(2) For those cosmetic ingredients which are also subject to other
existing safety reviews, their inclusion and priority shall be determined pursuant
to paragraph (i) of this section.
(b) The tentative priority list(s) shall be made publicly available and 90
days will be provided for public comment on it.
(c) The Expert Panel shall review the tentative priority list(s) and all
comments received on it, make any revisions it concludes appropriate, and adopt
a final priority list(s). The final priority list(s) shall determine the `order
in which cosmetic ingredients are reviewed under the Cosmetic Ingredient Review.
The Expert Panel may at any time revise the final priority list(s) either to add
new ingredients or to revise the priority of existing ingredients.
(d) On the basis of the tentative and final priority list(s) the Scientific
Coordinator shall develop or obtain Scientific Literature Reviews for each cos-
meti~ ingredient (or, where appropriate, closely related groups of cosmetic
ingredients), which shall consist of a bibliography of the domestic and foreign
toxicological literature and any other major domestic and foreign scientific
literature, a description of each literature reference, and a summary of the
information found for each ingredient.
(1) The Scientific Coordinator may either contract for the preparation
of each Scientific Literature Review or prepare it himself.
(2) As soon as it is available, each Scientific Literature Review will
be made public and 90 days will be provided for public comment on it.
(3) If the Scientific Coordinator concludes that there is insufficient
scientific literature to justify the preparation of a Scientific Literature Review,
the Administrator shall give public notice that no Scientific Literature Review
will be prepared for the ingredient involved.
(e) Upon the public notice of the availability of a Scientific Literature
Review, or that no Scientific Literature Eeview will be prepared, all interested
persons will be provided 90 days to submit to the Administrator data, information,
and views relevant to the safety of the cosmetic ingredient involved. A person
may submit any particular piece of information without identifying the source
of that information. To be considered, ten copies of the data and views,shall be
submitted, preferably bound, indexed, and on standard size paper (approximately
8 1/2 by 11 inches). All submissions shall be in the following format:
COSMETIC INGREDIENT REVIEW INFORMATION
I. The CTPA adopted name(s) and tradename(s) of the cosmetic
ingredient(s) involved, the name of the manufacturer, and if it
does not meet the specifications in any of the information sources
designated in the CTFA Cosmetic Ingredient Dictionary a statement
to that effect and the specifications that are applicable.
II. Comments, if any, on the completeness and accuracy of the
Scientific Literature Review for the ingredient.
III. A statement setting forth the number of products con-
taining the ingredient manufactured or distributed by the person
24-600 0 76 - 6
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108
making the submission, and the pertinent letter for each indica-
ting the range of the concentration of the ingredient for each
product, as is shown in the information submitted to the Food and
Drug Administration on Form FD-2512 (Cosmetic Product Ingredient
Statement), 21 C.F.R. 720.4(d) (1).
IV. Animal safety data.
A. All animal safety data not included in the Scientific
Literature Review on the individual cosmetic ingredient.
B. All animal safety data not included, in the Scientific
Literature Review on combinations of the individual Cosmetic
ingredient.
C. All animal safety data not included in the Scientific
~.iterature Review on cosmetic products or other products con-
taining the individual cosmetic ingredient as one component.
V. Human safety data (including exposure during clinical
testing, in occupational settings, and through product use).
A. All human safety data not included in the Scientific
Literature Review on the individual cosmetic ingredient.
B. All human safety data not included in the Scientific
Literature Review on combinations of the individual cosmetic
ingredients.
C. All human safety data not contained in the Scientific
Literature Review on cosmetic products or other products con-
taining the individual cosmetic ingredient as one component,
including results of significant human experience during marketing.
Such data may include relevant Forms FD-2704 (Cosmetic Product
Experience Report), FD-2705 (Cosmetic Product Unusual Experience
Report), and FD-2706 (Summary Report of Cosmetic Product Rxperi-
ence by Product Categories), 21 .C.F.R. Part 730.
VI. Other Relevant Safety Information.
VII. Conditions of use.
A. A statement that the ingredient is or is not used in
a cosmetic which falls into the following general use classifi-
cations.
1. Eye area use.
2. Subject to incidental ingestion.
3. Subject to incidental inhalation.
4. Mucous membrane use.
5. All other uses ~ skin, hair, and nails).
B. A statement indid~t'ing the use classifications for each
of the products in which the ingredient is used by the manufac-
turer or distributor, as specified iTt Food and Drug Administra-
tion Form FD-25l2 (Cosmetic Product Ingredient Statement), 21
C.F.R. 720.4(c).
C. Information on any other relevant conditions of use
~ directions for use an4 against misuse).
VXII. A summary of the data and views setting forth the
rationale for the conclusion that the ingredient is or is not
safe for its intended use.
(f) Upon the public notice of the availability of a Scientific Literature
Review, CTFA and any other interested person may submit to the Administrator a
chemical description of the ingredient involved, if one is available.
(g) Upon expiration of the time permitted for receipt of all of the perti-
nent data and information, the Scientific Coordinator shall prepare a final
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compilation of relevant data and information for presentation to the Expert Panel.
That compilation shall include:
(1) The Scientific Literature Review.
(2) All comments received on the Scientific Literature
Review.
(3) All submissions of data and information not con-
tained in the Scientific Literature Review.
(4) All chemical descriptions submitted.
(h) The Expert Panel may, in its discretion, accept late submissions and
new data relating to any ingredient at any time prior to its tentative report on
that ingredient.
(i) To minimize duplication of effort, the inclusion and priority of cog-
* metic ingredients which are also subject to other existing safety reviews shall be
* deterznined as fàllows except with respect to any specific ingrèd~ent fot which the
Expert Panel, with the approval of the Steering Committee, has assigned a special
priority for good cause.
(1) Color Additives. All color additives shall be excluded from the
Cosmetic Ingredient Review because their safety is determined under Section 706 of
the Act and 21 C.F.R. Parts 8 and 9.
(2) OTC Drug Active Ingredients. The Expert Panel shall defer evalu-
ation of a cosmetic ingredient which is also used as an active ingredient in an
OTC drug, and thus is subject to review under t1~e Food and Drug Administration
OTC drug review established in 21 C.F.R. Part 330, until after the final monograph
for the relevant OTC drug Category (or, if there is more than one, the last rele-
vant OTC drug category) is published by the Food and~flrug Administration pursuant
to 21 C.F~.R. 330.10(a) (9) and shall then determine whether all safety information
relevant to cosmetic use of the ingredient was available to the OTC drug review
and whether the cosmetic ~se of the ingredient presents any additional safey con-
siderations not adequately covered by the OTC drug review. The Expert Panel shall
adopt those conclusions of the OTC 4rug review which it concludes adequately cover
cosmetic use of the ingredient and shall conduct its own evaluation of those cos-
metic uses not adequately covered by the OTC drug review.
(3) Food Flavors. The Expert Panel shall defer evaluation of a cos-
metic flavor ingredient which is also used as a flavor in food, and thus is sub-
ject to review under the FASEB-FDA review of flavor ingredients which are GRAS or
food additives described in ~art II of the Federal Register of July 26, 1973
(38 F.R. 20036 et seq.) and Part II of the Federal Register of September 23, 1974
(39 F.R. 34172 et seq.), until after the final regulation for the ingredient is
published by the Food and Drug Administration and shall then determine whether all
safety information relevant to cosmetic use of the ingredient was available to the
FASEB-FDA review and whether the cosmetic ~ise of the ingredient presents any
additional safety considetations.not adequately covered by the FASEm-FDA review.
The Expert Panel shall adopt those conclusions of the FASEB-FDA review which it
concludes adequately cover cosmetic use of the ingredient and shall conduct its
own evaluation of those cosmetic uses not adequately covered by the FASEB-FDA
review.
(4) GRASFood Ingredients. The Expert Panel shall defer evaluation of
C Cosmetic ingredient which is also used as an ingredient in a food on the basis
that it has been determined to be GRAS or subject to a prior sanction, and thus
is subject to review under the FASEB-FDA review described in Part TI of the
* Federal Register for July26, 1973 (38 F.R. 20036 et seq.) and Part II of the
Federal Register for September 23, 1974 (39 F.R. 34172 et seq.), until after the
final regulation is promulgated for the ingredient by the Food and Drug Ad~ini-
stration and shall then determine whether all safety information relevant to
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cosmetic use of the ingredient was available to the FASEB-FDA review and whether
the cosmetic use of the ingredient presents any additional safety considerations
not adequately covered by the FASEB-FDA review. The Expert Panel shall adopt those
conclusions of the FASEB-FDA review which it concludes adequately cover cosmetic
use of the ingredient and shall conduct its own evaluation of those cosmetic uses
not adequately covered by FASEB-FDA review.
(5) Food Additives. In evaluating a cosmetic ingredient which is also
used as a food additive, and thus is subject to a food additive regulation pro-
mulgated by the Food and Drug Administration in 21 C.F.R. Part 121, the Expert
Panel shall review the food additive petition and all related documents which the
Food and Drug Administration makes available to determine whether all safety infor-
mation relevant to cosmetic use of the ingredient was available to the Food and
Drug Administration and whether the cosmetic use of the ingredient presents any
additional safety considerations not adequately covered by the Food and Drug
Administration approval of the food additive regulation. The Expert Panel shall
adopt those conclusions of the Food and Drug Administration approval which it
concludes adequately cover cosmetic use of the ingredient and shall conduct its
own evaluation of those cosmetic uses not adequately covered by the Food and Drug
Administration approval.
(6) Fragrance Ingredients. All fragrance ingredients shall be exclud-
ed from the Cosmetic Ingredient Review because their safety is being determined
by the Research Institute for Fragrance Materials (RIFM).
(7) Food and Drug Administration Regulations. All matters which are
the subject of a final regulation promulgated by the Food and Drug Administration
shall be excluded from the Cosmetic Ingredient Review.
(8) New Drug Applications. In evaluating a cosmetic ingredient which
is also used as an inactive or active ingredient in an OTC or prescription drug
for which the Food and Drug Administration has at any time approved or permitted
to become effective a New Drug Application, the Expert Panel shall review all
related documents which the Food and Drug Administration makes available to
determine whether all safety information relevant to cosmetic use of the ingredi-
ent was available to the Food and Drug Administration and whether the cosmetic
use of the ingredient presents any additional safety considerations not adequately
covered by the Food and Drug Administration action on the New Drug Application.
The Expert Panel shall adopt those conclusions of the Food and Drug Administration
action which it concludes adequately cover cosmetic use of the ingredient and
shall conduct its own evaluation of those cosmetic uses not adequately covered by
the Food and Drug Administration action.
(j) An ingredient shall be reviewed in accordance with the priority
assigned to it pursuant to this section. -
(1) Upon presentation of all pertinent data and information to the
Expert Panel pursuant to paragraph (g) of this section, an ingredient shall be
considered to be under review by the Expert Panel. An ingredient shall remain
under review by the Expert Panel until the Expert Panel issues a final report on
it pursuant to Section 44 of these procedures.
(2) If the Expert Panel concludes that the available data and infor-
mation are insufficient to determine such ingredient, under each relevant condi-
tion of use, as either safe or not safe, it shall decide the type of further data
or information required and the time period within which it might reasonably be
obtained. Any such decision shall be set forth fully in the minutes of the Expert
Panel meeting.
(A) Upon the public availability of the minutes of any such
meeting pursuant to Section 51 of these procedures, the Administrator shall give
public notice of any such decision.
(B) Within 90 days after such public- notice, any interested
person may inform the Expert Panel that work adequate and appropriate to resolve
the questions raised about the ingredient will be undertaken.
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(C) A progress report on any work undertaken pursuant to such a
commitment shall be filed with the Cosmetic Ingredient Review every January 1 and
July 1 until completion.
(0) if such a commitment is undertaken, the ingredient shall
remain under review by the Expert Panel and the Expert Panel shall defer prepara-
.tion of a tentative report pursuant to Section 43 of these procedures and a final
report pursuant to Section 44 of these procedures until completion of the work
involved, unless the Expert Panel determines that the work is not being pursued
promptly and diligently or that interim results indicate a reasonable likelihood
that a health hazard exists.
(E) upon completion of the work undertaken pursuant to such a
commitment, the Expert Panel shall review all available data and information and
shall issue a tentative report pursuant to Section 43 of these procedures and a
final report pursuant to Section 44 of these procedures.
(3) If the Expert Panel determines pursuant to paragraph (j) (2) of
this section that the available data and information are insufficient to determine
such ingredient, under any specific condition of use, as either safe or not safe,
and no one undertakes the work to obtain the required data and information in
accordance with paragraph (j) (2) of this section, the Expert Panel shall determine
that there is a lack of information needed to make a determination and insuff i-
cient industry interest in the ingredient at that time to justify obtaining the
needed information and shall issue a tentative report pursuant to Section 43 of
these procedures and a final report pursuant to SeCtion 44 of these procedures.
Section 31. Meetings of the Expert Panel.
(a) The Expert Panel will meet as gften and for as long as is appropriate
to review the data submitted to it and to prepare a report containing its con-
clusions and recommendations with respect to the safety of cosmetic ingredients.
(b) The Expert Panel shall co~ivene at the call of the Chairman. The
Administrator shall be responsible for giving appropriate notice to all Expert
Panel members and liaison representatives for distributing all pertinent infor-
mation, for all travel and meeting arrangements, and for similar administrative
support.
(c) All Expert Panel meetings shall be held in Washington, D.C., or the
immediate vicinity, unless there are compelling reasons for a different location.
A different location may be approved by the Steering Committee for good cause.
(d) The Expert Panel may,, with the approval of the Steering Committee, con-
duct on-site visits relevant to the work of the Expert Panel.
(a) A quorum for the Expert Panel shall be five members of the Expert
Panel. Any matter before the Expert Panel shall be decided by a majority vote of
the members present at the time, except that any final report shall be voted upon
by all current members of the Expert Panel. Any current member of the Expert
Panel may file a Separate report with additional or minority views.
(f) Subject to availability of space, any interested person may attend any
portion of any Expert Panel meeting which is not closed.
(g) Any portion of a meeting shall be closed by the Expert Panel Chairman
when matters which have been determined closed in accordance with Section 36 of
these procedures are to be discussed. Where a portion of the meeting is closed,
the closed portion shall be held after the conclusion of the open portion when-
ever practicable.
(h) Any Expert Panel member or liaison representative may take notes during
Expert Panel meetings and report and discuss the deliberations of the Expert Panel
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after a meeting is completed and before official minutes or a report is available,
within such rules and regulations as are adopted by the Expert Panel in accordance
with Section 32 of these procedures.
(1) There shall be no attribution of individual views expressed in a
closed session or revealing of numerical votes.
(2) There shall be no reporting or discussion with respect to any
particular matter where the Expert Panel specifically so directs, ~ where
deliberations are incomplete or involve a sensitive decision whichih~uld not be
released prematurely.
(3) There shall be no reporting or disclosure with respect to data or
information prohibited from public disclosure pursuant to Section 51(b) of these
procedures.
(4) Any notes or minutes kept or report prepared by any Expert Panel
member or liaison representative shall have no status or effect whatever unless
adopted as or incorporated into the official minutes or report by the Expert Panel.
It shall be the responsibility of each Expert Panel member and liaison representa-
tive to make certain that the official minutes and reports are complete and
accurate and fully reflect what happened at any meeting he attended.
Section 32. Additional Rules for the Expert Panel.
(a) In addition to the rules established in these procedures, the Expert
Panel may, with the concurrence of the Steering Committee, adopt additional rules
which are not inconsistent with these procedures.
(b) Such additional rules shall be included in the minutes of the meeting
when adopted and in the materials compiled pursuant to Section 27 of these pro-
cedures and shall be available for public disclosure pursuant to Section 51(a) of
these procedures.
Section 33. COnsultation by the Expert Panel with Other Persons.
(a) The Expert Panel may consult with any person who may have data, infor-
mation, or views relevant to any matter pending before the Expert Panel and, with
the approval of the Director, may compensate such person and reimburse his
expenses.
(b) Any interested person may submit to the Expert Panel a written request
that it consult with specific persons who may have data, information, or views
relevant to any matter pending before the Expert Panel. Such requests shall state
why the specified person should be consulted and, if payment is requested, why
the views of that person cannot reasonably be furnished to the Expert Panel by
any other means. The Expert Panel, may, in its discretion deny or grant such a
request and, if payment is requested, with the approval of the Director, may
compensate such person and reimburse his expenses.
Section 34. Portions of Expert Panel Meetings.
An Expert Panel meeting shall have the following separable portions:
(a) The open public hearing. Every Expert Panel meeting shall include an
open portion which shall constitute a public hearing during which any interested
person may present data, information, or views, orally or in writing, relevant to
the Expert Panel's agenda or other work. Such hearing shall be conducted in
accordance with Section 39 of these procedures.
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(b) The open panel discussion. The Expert Panel shall discuss any matter
pending before it in an open portion of its meeting unless the meeting has been
closed with respect to that matter pursuant to Section 36 of these procedures.
No public participation is permissible during the open panel discussion portion of
the meeting except with the consent of the Chairman of the Expert Panel.
(c) The closed presentation of data. Data~ and information which are pro-
hibited from public disclosure pursuant to the provisions bf Section 51(b) of
these procedures shall be presented to the members of the Expert Panel in a closed
portion of its meeting.
(d) The closed panel deliberations. Deliberations with respect to matters
pending before the Expert Pane~. may b& made in a closed portion of its meeting
upon an appropriate determination by the chairman pursuant to Section 36 of these
procedures.
Section 35. Notice of Public Hearing and Meeting of the Expert Panel.
(a) At least fifteen days before any meeting of the Expert Panel, the
Administrator shall give public notice of such meeting.
(b) Such notice shall include:
(1) The date, time, and place of the hearing and meeting.
(2) A list of all agenda items.
(3) If any portion of the meeting is closed, a statement of the time
of the open and closed portions.
(4) The time specifically set aside for oral statements by interested
persons and for other public participation.
(5) The name, address, and telephone number of the persons specif i-
cally responsible for the administrative support for that hearing and meeting.
(6) A statement that written submissions may be made to the Expert
Panel at any time pursuant to Section 38 of these procedures.
Section 36. Determination to Close Portions of Expert Panel ~4eetings.
(a) No Expert Pane~1. meeting shall be entirely closed unless no one requests
an opportunity to make a presentation at the open portion for public participation.
A portion of an Expert Panel meeting may be closed only pursuant to a determina-
tion by the Chairman, reflected in the minutes of the meeting, in accordance with
this section.
(b) The following rules shall govern the closing of a portion of an Expert
Panel meeting:
(1) Any determination to close a portion of a meeting shall restrict
such closing to the shortest time possible consistent with the policy established
in this section.
(2) Portions of meetings during which matters are considered that are
prohibited from public disclosure pursuant to Section 51(b) o~ these procedures
shall be closed.
(3) Portions of meetings during which the Expert Panel deliberates on
the safety of cosmetic ingredients may be closed upon the determination of the
Chairman that it is essential to close such portion of such meeting to protect
the free exchange of internal views and to avoid undue interference with Expert
Panel operations.
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(ö) A matter which is properly considered in en Open portion of an Expert
Panel meeting may instead be considered in a closed portion only if it is so
inextricably intertwined with matters to be discussed in a closed portion that it
is not feasible to separate them or discussion of the matter in an open portion
would compromise or impinge upon the matters to be discussed in the closed portion.
(d) A closed portion of an Expert Panel meeting shall be attended only by
Expert Panel members, liaison representatives, and the Cosmetic Ingredient Review
employees, except as provided in Section 34(c) of these procedures for presenta-
tion of data and information which are prohibited from public disclosure pursuant
to Section 51(b) of these procedures. Any person making a presentation described
in Section 34(c) may be accompanied by a reasonable number of employees, consul-
tants, GF other persons with whom he has a commercial arrangement. If any person
other than an Expert Panel member, a liaison representative, a Cosmetic Ingredi-
ent Review employee, or a person making a presentation described in Section 34(c)
attends a portion of an Expert Panel meeting, that portion shall be open to
attendance by any interested person.
Section 37. Administrative Remedies.
Any person who alleges non-compliance by the Expert Panel or the Cosmetic
Ingredient Review staff with any provision of these procedures may request
appropriate relief from the Steering Committee.
Section 38. Written submissions to the Expert Panel.
(a) Ten copies of all written submissions for the Expert Panel shall be
sent to the Administrator, unless an applicable public notice specifies otherwise.
(b} At the request of the Expert Panel, the Administrator may at any time
issue a public notice requesting the submission to the Expert Panel of written
data, information, and views pertaining to any matter being reviewed by the Expert
Panel. Such notice shall specify the format in which the submission shall be
made, the number of copies to be submitted, and the time within which submission
shall be made.
(c) Any interested person may submit to the Expert Panel, through the
Administrator, written date, information, or views on any matter being reviewed
by the Expert Panel. Voluminous data shell be accompanied by a summary.
(1) Any such submission shall be distributed to each Expert Panel
member and liaison representative, either by mail or at the next Expert Panel
meeting, end shall be considered by the Expert Panel in its review of the matter.
(2) The Expert Panel may establish, and shall give public notice of,
a cut-off date after which submissions relating to any matter shall no longer
be received or considered.
(d) The Scientific Coordinator, through the Administrator, shell provide
for the Expert Panel and liaison representatives all scientific data and informa-
tion he concludes to be relevant to any matter being reviewed by the Expert Panel.
Any member of the Expert Panel or liaison representative shall, upon request, also
be provided any additional material available to the Cosmetic Ingredient Review
which he believes appropriate for an independent judgment on the matter, ~
raw data underlying any summary or report.
Section 39. Conduct of a Public Hearing Before the Expert Panel.
(a) For each Expert Panel meeting, the open portion for public participa-
tion which constitutes a public hearing pursuant to Section 34(a) of these
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procedures, shall be at least one hour long unless the public participation does
not last that long, and may last for whatever time the Expert Panel Chairman
determineS will facilitate the work of the Expert Panel. The public notice issued
pursuant to Section 35 of these procedures shall designate the time specifically
reserved for such public hearing, which shall ordinarily be the first portion of
the meeting. Further public participation in any open portion of the meeting
pursuant to Section 34(b) of these procedures shall be solely at the discretion
of the Expert Panel Chairman.
(b) Any interested person who wishes to be assured of the right to make an
oral presentation at a particular Expert Panel hearing shall so inform the Admini-
strator or other designated Cosmetic Ingredient Review employee, orally or in
writing, prior to the Expert Panel meeting.
(1) Such person shall state the qeneral nature of the presentation
and the approximate time requested. Whenever possible, all written data and infor-
mation to be discussed by that person at the Expert Panel hearing shall be fur-
nished in advance to the Administrator or other desiqnated Cosmetic Ingredient
Review employee. Such written material shall be mailed to the Expert Panel members
and liaison representatives in advance of the meeting if time permits, and other-
wise will be distributed to- the Expert Panel members and liaison representatives
when they arrive at the meeting. Such mailing or distribution shall be undertaken
only by the Cosmetic Ingredient Review staff unless the Administrator specifically
permits the person making the presentation to mail or distribute such material.
(2) Prior to the Expert Panel hearing, the Administrator or other
designated Cosmetic Ingredient Review employee shall determine the amount of time
allocated to each person for his oral presentation and the time that oral
presentation is scheduled to begin. Each person shall be so informed in writing
or, if the time prior to the hearing is short, by telephone. Joint presentations
may be required by persons with common interests.
(c) The Chairman of the Expert Panel shall preside at the hearing and shall
be accompanied by other Expert Panel members and liaison representatives who
shall serve as a panel in conducting the hearing
(d) Each person may use his allotted time in whatevè~ way he wishes, con-
sistent with a reasonable and orderly hearing. A person may be accompanied by
any number of additional persons, and may present any written data, information,
or views for the consideration of the Expert Panel.
(e) If a person is not present at the time specified for his presentation,
the persons following will appear in order. An attempt will be made to hear any
such person at the conclusion of the hearing. Any interested persons attending
the hearing who did not request an opportunity to make an oral presentation shall
be given an opportunity to make an oral presentation at the conclusion of the
hearing, in the discretion of the Chairman, to the extent that time permits.
(f) The Chairman, other members of the Expert Panel, and liaison representa-
tives may question any person during or at the conclusion of his presentation. No
other person attending the hearing may question a person making a presentation.
The Chairman may allot additional time to any person when he concludes that it is
justifiable, but may not reduce the time allotted for any person without his con-
sent.
(g) Public participants may question an Expert Panel member or a liaison
representative only with that person's permission and only about matters before
the Expert Panel.
(h) The hearing shall be informal in nature, and the rules of evidence shall
not apply. No motions or objections relating to the admissibility of data, infor-
mation, and views shall be made or considered, but other participants may comment
upon or rebut all such data, information, and views. No participant may interrupt
the presentation of another participant at any hearing for any reason.
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~ection,4O. Minutes and Reports of Expert Panel Meetings.
(a) The Executive Secretary or other designated Cosmetic Ingredient Review
employee shall prepare detailed minutes of all Expert Panel meetings, except that
less detailed minutes may be prepared for open portions of meetings which are
transcribed or recorded. The accuracy of all minutes shall be approved by the
Expert Panel and certified by the Expert Panel Chairman. Such approval and
certification may be accomplished by mail and by telephone.
(b) The minutes shall include:
(1) The time and place of the meeting.
(2) The names of the Expert Panel members, the Cosmetic Ingredient
Review staff, and the liaison representatives as well as the names and affilia-
tions or interests of public participants attending the meeting.
(3) A copy of or reference to all written information made available
for consideration by the Expert Panel at the meeting.
(4) A complete and accurate description of matters discussed and
conclusions reached. Such description shall be kept separately for the following
portions of the meeting to facilitate their public disclosure: the open portion
specified. in Section 34(a.) and (b), any closed portion during which a presentation
is made pursuant to Section 34(c), and any closed deliberative portion pursuant
to Section 34(d). The minutes of a closed deliberative portion of a meeting shall
not refer to Expert Panel members by name, except upon their request, or to data
or information prohibited from public disclosure under Section 51(b) of these
procedures. Any such inadvertent references which do occur shall be deleted
prior to public disclosure.
(5) A copy of or reference to all reports received, issued, or
approved by the Expert Panel.
(6) The extent to which the meeting is open and closed to the public.
(7) The extent to public participation, including a list of members
of the public who presented oral or written statements.
Section 41. Transc~pts of Expert Panel Meetings.
(a) A transcript or recording is not required for any portion of an Expert
Panel meáting.
(b) The Expert Panel shall decide whether any portion or all of its meet-
ings shall be transcribed or recorded and, if so, by what means. Any such tran-
scription or recording shall be arranged by the Administrator.
(c) If a transcript or recording of an open portion of an Expert Panel
meeting is made by the Cosmetic Ingredient Review staff, or is made by an inter-
ested person and is submitted to the Cosmetic Ingredient Review, it shall be
included in the record of the Expert Panel proceedings.
(d) If a transcript or recording of any closed portion of an Expert Panel
meeting is made, it shall not be included in the records of the. Expert Panel pro-
ceedings~ that are available for public disclosure. Any. such transcript or
recording shall be retained as confidential. The Chairman of the Expert Panel
may, in his discretion, permit discussion without transcription or recording
during any closed portion of an Expert Panel meeting that is otherwise being
transcribed or recorded.
(e) Any person attending any open portion of an Expert Panel meeting may,
consistent with the orderly conduct of the meeting, record or otherwise take his
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own transcript of the meeting. No person attending any closed portion of any
Expert Panel meeting may record or otherwise take his own transcript of the
meeting, except for an official transcript or recording arranged by the Administra-
tor.
Section 42. Expert Panel Determinations.
On the basis of all data and information submitted to it, the Expert Panel
shall determine whether each ingredient, under each relevant condition of use, is
safe, or not safe, or there is a lack of information needed to make a determina-
tion and insufficient industr~r ini~erest in the ingred~ent at that time to justify
obtaining the needed information. Upon making such a determination, the Expett
Panel shall issue a tentative report pursuant to Section 43 of these procedures
and a final report pursuant to Section 44 of these procedures.
Section 43. Tentative Report of the Expert Panel.
(a) Prigr to issuing a final report as described in Section 44 of these
procedures, the Expert Panel shall issue a tentative report.
(b) The tentative report of the Expert Panel shall meet all of the
re~ui~ements established for a final report in Sections 44 (a) and (b) of these
procedures.
(c) The public notice of the availability of the tentative report shall
provide 90 days within which any interested person may submit comments on the
tentative report and a request for oral hearing before the Expert Panel on the
tentative report.
(d) An oral hearing shall ~e granted by the Expert Panel on a tentative
report of the Expert Panel for good cause shown. Any such oral hearing shall be
conducted pursuant to the provisions of Section 39 of these procedures. -
Section 44. ~ Report of the Expert Panel.
(a) With respect to each cosmetic ingredient (or, where appropriate,
c~osely related group of cosmetic ingredients), the Expert Panel shall issue a
final report. The final report shall state the determination o~ the Expert Panel
in accordance with Section 42 of these procedures with respect to each ingredient
and any relevant conditions of its use..
(b) The final report shall contain the complete conclusions and recommen-
dations of the Expert Panel with respect to the ingredient involved, including a
full explanation of the reasons for those conclusions and recommendations and
references to the scientific information bn which the Expert Panel relies.
(c) The final report shall refer and respond to each point made in any
submission or oral statement made with respect to the tentative report pursuant
to Section 43 of these procedures.
(d) The Scientific Coordinator shall arrange for the publication of eacI~
final report in an appropriate scientific journal. The Administrator shall other-
wise arrange for public dissemination of the final report.
Section 4S. Amendment of a~ F'inal Report.
(a) Any interested person who believes that a final report is incorrect
may petition the Expert Panel to amend the final report to correct such error.
The Administrator shall give public notice of any such petition and all pro-
ceedings of the Expert Panel with respect to any such petition shall be conducted
pursuant to these procedures.
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(b) A petition to amend a final report pursuant to this section shall
ordinarily be based upon new data and information not previously reviewed by the
Expert Panel. Such a petition shall be used primarily after the further data and
information requested by the Expert Panel in the final report with respect to an
ingredient, under each revelant conditiqn of use, has been obtained, so that the
Expert Panel can proceed with final determination with respect to that ingredient*
or condition.
(c) A determination by the Expert Panel with respect to a petition for
amendment of the final report shall be handled in the same way as the initial
determination by the Expert Panel. The Expert Panel shall first issue a tentative
report in accordance with Section 43 and then a final report in accordance with
Section 44.
~rt E -- Public Notice and Availability of Records
Section 50. Public Notice.
(a) The Administrator shall give public notice of the availability of all
Scientific Literature Reviews, the meetings of the Expert Panel, decisions and
reports of the Expert Panel, and all other similar information, in both of the
following two ways:
(1) Such notice shall be mailed to a permanent mailing list consisting
of representative members of the press (including interested newspapers, trade
press, consumer publications, professional publications, and others) and represen-
tative interested organizations (including consumer, professional, and business
organizations).
(2) Such notice shall also be given by mailing it to specific individ-
uals who have demonstrated a continuing interest through direct participation in
the Cosmetic Ingredient Review except for individuals who are members of organi-
zations to which notice is provided.
(b) Any interested intividual or or9anization may request that it be placed
on the mailing list for all public notices by written application to the Adam-
istratàr.. Any such request shall be accompanied by a statement of the need of
such individual for such notices. The Steering Committee may, in its discretion,
impose a fee for providing such notices to all individuals, which shall be no
greater than the actual expense involved in providing them.
Section 51. Availability of Records for Public Disclosure.
(a) The following records relating to the Cosmetic Ingredient Review shall
be available for public disclosure at the following time, except as otherwise
provided in paragraph (b) of this section:
(1) The minutes of each Steering Committee meeting, after they have
been approved by the Steering Committee and certified by the Steering Committee
Chairman.
(2) Each Scientific Literature Review, at the time it is completed and
available in printed form.
(3) Each chemical description, at the time that it is submitted to the
Administrator.
(4) Each submission of safety information pursuant to Section 30(e) of
these procedures, at the time it is received by the Administrator.
(5) The written information made available for consideration by the
Expert Panel at any meeting, at the same time that it is made available.
(6) Any transcript or recording of any open portion of an Expert
Panel meeting, as soon as it is available.
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(7) The minutes of any open portion of an Expert Panel meeting, after
they have been approved by the Expert Panel and certified by the Expert Panel
Chairman.
(8) All written data, information, or views submitted to the Expert
Panel at any open portion of a meeting, as soon as they are so submitted.
(9) The minutes or portions thereof of any closed Executive portion of
a meeting:
(i) For any matter not directed tobe maintained as confidential
pursuant to Section 31(h) (2) of these procedures, after they have been approved
by the Expert Panel and certified by the ~Expert Panel Chairman.
(ii) For any matter dir~c~ed to be maintained as confidential
pursuant to Section 31(h) (2) of these ~ocedures, after the matter relevant to
those minutes or portions thereof as~cted upon by the Expert Panel or upon a
determination by the Expert Panel that such minutes or portions thereof may be
made available for public disclosure without undue interference with the opera-
tions of the Expert Panel.
(10) Any formal advice o~ report of the Expert Panel, after it has
been issued by the Expert Panel.
(11) Any other Expert Panel records relating to the matter involved,
except transcripts and recordings of closed portions of Expert Panel meetings,
after the matter relevant to those records is acted upon by the Expert Panel, or
upon a determination by the Expert Panel that such records may be made available
for public disclosure without undue interference with the operations of the
Expert Panel.
(b) The following records relating to the Cosmetic Ingredient Review shall
not be available for public disclosure:
(1) Records relating to any cosmetic ingredient which has been deter-
mined by the Food and Drug Administration tO be exempt from public disclosure
pursuant to 21 C.P.R. 701.3(a) and 720.8(a).
(2) Adverse reaction reports, product experience reports, consumer
complaints, and other similar data and info]~mation shall be available for public
disclosure only in accordance with the regulations established by the Food and
brug Administration for public disclosure of such data and information in 21 C.F.R.
4.111(c) (3).
(3) All data and information relative tO the nomination and selection
of the members of the Expert Panel and liaison representative, in accordance with
Section 21(e) of these procedures.
(4) A transcript or recording of any closed portion of an Expert Panel
meeting, in accordance with Section 41(d) of these procedures.
Section 52. Public Documents Room.
(a) The Administrator shall establish a Public Documents Room, where one
copy of all records available for public disclosure relating to the Cosmetic
Ingredient Review shall be stored and available for public review. The Public
Documents Room shall have adequate space for interested persons to examine such
documents.
(b) Any person who uses the Public Documents Room shall sign a log showing
his name, affiliation, time of entry and exit, and a general description of the
documents reviewed.
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-21-
Section 53. Public Inquiries and Requests for the Cosmetic Ingredient Review
Records.
(a) Public inquiries on all matters relating to the Cosmetic Ingredient
Review shall be directed to: Administrator, Cosmetic Ingredient Review,
1133 Fifteenth Street, N.W., Washington, DC 20005, Telephone (202) 331-0651.
(b) All requests for records relating to the Cosmetic Ingredient Review,
including records of the Expert Panel, shall be made to the Administrator.
(c) Copies of records that are publicly available pursuant to these pro-
cedures shall be made, upon request, for a fee that will reflect the actual cost
of the labor and materials involved. The Administrator, with the approval of the
Steering Committee, shall maintain a current price schedule for such copying.
PAGENO="0127"
121
Mr. Moss. Thank you very much.
Mr. Gore?
Mr. GORE. Thank you, Mr. Chairman.
I appreciate your testimony, Mr. Merritt. I appreciate your wilhing~
ness to help us get to the truth in this matter.
I think you put it into the context that I think this issue arises
within, cancer is not the second leading cause of death in the country.
The new figures indicate that as much as 90 percent of all cancers in
America may be caused by substances put into the environment by
man.
Around 33 million women use hair dyes. Now tests have indicated
that many ingredients of these hair dyes are carcinogenic in animals.
You dispute the test methodology in your testimony this morning.
One reference. you made was to the Yale study as supporting your
characterization of these tests. However, I have an abstract of the
Yale study which indicates that cosmetologists were found to have
an increased risk of acute leukemia.
In October of last year the Director of the Connecticut Cancer
Epidemiology program wrote to the vice president for research of
Clairol informing Clairol of the results of this test saying that cosmeto-
logists had more cancer of the uterus and cervix and that they had
higher r~tes of acute leukemia.
Now, the other tests show or appear to show that these ingredients
are carcinogenic in animals. They have shown, for some time, that
these ingredients are mutagenic and that they have the capacity to
cause birth defects.
With 33 million women using these products, how can you justify
saying that the law does not need to be changed?
Let me read to you from the present law. I know you are very
familiar with it. 21 U.S.C. Section 361(a),
If food and drug and cosmetic contains any poisonous or deleterious substance
which may render it injurious to users under the conditions of use prescribed in
the labeling thereof or under such conditions of use as are customary or usual,
provided that this provision shall not apply to cold tar hair dye.
I have only been here a year, but I know bow the lobbying process
works. I have seen it work already. It is obvious to me what happened.
Your lobby was effective in getting an extension of your products and
your industry. Now the tests indicate that that exception is not
warranted at all. Why do you think that law should not be changed?
Mr. MERRITT. Mr. Gore, you have raised two basic questions in
your comments. One of these deals with the question of science as
embodied in a specific re~port. The other relates to law.
With your indulgence I would first like to ask Dr. Corbett to respond
to the scientific question which you have raised in that specific
epidemiology study.
M~. GORE. That would be fine.
Dr. CORBETP. In the Yale study-and this was. a comparison be-
tween 12,000 cosmetologists and beauticians and 12,000 school
teachers-the results found an excess of cervical cancer and of acute
leukemia among the cosmetologists... Dr. Meigs said-and I think
this is well-supportable-that it is well known that. cervical cancer
is higher among lower socio-ecónomic groups than it is among the
higher socio-economic groups.
PAGENO="0128"
122
By contrast, among the teacher group there is a higher level of
breast cancer. This, again, runs in line with the expected result based
on these socio-economic statuses.
In respect to the acute leukemia, Dr. Meigs said in his report that
he believed that this was due to the surprising absence of any acute
leukemia among the teacher group and that this was a subject for
further investigation and not a subject for conclusion to be made at
this time.
Mr. :G ORE. How can you say it's safe if the conclusion is that further
investigation is needed? You say there is no evidence at all-
Dr. CORBETT. There have been other studies which one can relate
with the Yale study that show no excess leukemia.
Mr. GORE. What about the NCI tests? I want to get back to the
point of law but we have had many examples of testimony from
doctors who work for industries and who spend most of their time
telling the industry that products are safe. I want to know your
impression of the NCI test and the Ames test.
Dr. COREETT. First of all, I would like to point out that in spite of
the existence of 601 (a) which many people might claim exonerates
the hair coloring industry from doing anything at all, it was in fact
the industry that undertook the first, second, and third phases of
testing of hair dye ingredients or hair dye compositions for safety.
The safety studies carried out by the Cosmetic, Toiletry, and
Fragrance Association preceded the studies that were done by the
National Cancer Institute. They were done under conditions which
we believe to be more realistic. According to the NCI guidelines they
are more appropriate for evaluating the carcinogenicity of the material
under the conditions of use.
The NOT feeding study was a feeding study involving massive
doses. NOT determined initially the maximum dosage that could be
fed to an animal without resulting in 9 days-although in this case
I think it was considerably less than that-in more than a-10 percent
weight loss. No pathology was done on those animals to see whether,
other than weight loss, there had been any sort of acute damage done.
We question very much the level that was used in the NOT feeding
study. I believe we made a mistake in saying that the higher dose was
changed arbitrarily during the course of the study. What actually
happened was that the lower dose level of the original study was ehmi-
nated and a new and arbitrary higher dose group was inserted some
3 months after the beginning of the study.
In our laboratories I have carried out a short-term experiment in
which we fed the level used in the NOT study at the high-dose level
for 2,4 Diaminoanisole to rats. After 5 days granules appear in the
thyroid glands of the animals. These are not normal animals. We are
attempting at the moment to show, and we believe we will, that the
quantity fed resulted in a diversion of the thyroid stimulating hor-
mone. Again, the animals under those conditions would not be con-
sidered normal metabolic animals.
Mr. Moss. Excuse me. We will let you finish but when this question
is finished we will have to recognize the next member.
Mr. GORE. Go ahead and complete your answer.
Dr. CORBETT. Since the major observation in this test was that
there was a high level of thyroid cancer in male and female rats and
PAGENO="0129"
123
mice-that is four groups of animals-and a complete absence of in-
crease in that form of cancer in the lower dose group, we question
whether this particular test does not show indeed a threshhold level
below which the material is safe and, therefore, is not grounds on
which to say that this material represents a hazard to man.
Mr. GORE. Thank you.
Mr. Moss. The Chair recognizes the gentleman from New York,
Mr. Lent.
Mr. LENT. Thank you, Mr. Chairman.
Mr. Merritt, if you would refer to page 9 of your statement, you
indicate in the second paragraph that you agree with Dr. Upton's
testimony last Monday. In that testimony he said, at least in part
that because the NOT's animal tests showed that some hair dye in-
gredients cause cancer in laboratory animals that this constitutes pre-
sumptive risk in man.
I wonder whether you would agree with that statement and if so if
you could explain why you would, or why you would not if you do not
agree with it.
Mr. MERRITT. Here again, Mr. Lent, this is a scientific question
dealing with risks and presumption of theoretical risks. Perhaps, Dr.
Corbett might have a comment with respect to that.
Mr. CORBETT. In the absence of any other data, I would agree
entirely with Dr. Upton that any positive result in a bioassay study
is a presumptive risk. In other words, it raises th~ question: Is this
material safe?
The NCI bioassay program, as Dr. Upton said in his prepared
statement, was in fact a screening test that was regarded by its
originators as the cheapest and quickest way of sorting out chemicals
that needed further biological evaluation and those that did not.
It was not intended by the people who designed the tests that the
results of those tests should be used for regulatory purposes. I think
I should explain the reason for this.
If one is to carry out bioassay studies which are meaningful one
should really spend between 2 and 5 years studying the metabolism
of the material that is to be tested in order to see whether there are
changes as the dose changes and so on. This is expensive and tedious.
So it was felt, first,. that you would eliminate as many chemicals as
possible by doing the high-level feeding studies and then take those
that needed further evaluation and do more definitive studies on them.
Mr LENT Let me see if I understand this as a layman What you
are saying is that you are not in disagieement with Dr. Upton or even
the results of the NOT tests insofar as they were conducted. But what
you are saying is that they should not be applied to the hair dye in-
dustry because what we had here was simply an effort at screening or
weeding out the most potentially harmful ingredients and that this
screening process took place by massive ingestion by animals, labora-
tory animals, of these ingredients.
Has the NOT, so far as you are aware now, gone on to complete the
remaining analysis and testing of those ingredients found to be
presumptively harmful?
Mr. CORBETT. As far as I am aware the great purpose of the original
bioassay program, due to the pressures being applied on NOT, will
never be fulfilled. Essentially when they finished these massive maxi-
24-600 0 - 78 - 9
PAGENO="0130"
124
mum tolerated dose feeding studies they stopped studying those
chemicals at that point and have gone on to something else.
Possibly rightly I think that it is regarded that if a positive is found,
then the onus of demonstration of the safety of the material falls on
those people in society who wish to use it. I think that the cosmetic
industry has demOnstrated that it accepts its responsibility. We have
spent 10 years now doing animal tests. At every point during those 10
years we were engaged in some sort of animal testing on hair dye in-
gredients and formulations in order to establish their safety. We
believe that we had done this before the results of the NCI test
came out.
Mr. LENT. In all the years that you `have been conducting these
tests and that Mr. Merritt ~has been in this business and with the
increasing consumer awareness these days and the high incidence of
consumer liability cases, has there ever been a case that you know of or
that anyone on this witness panel would know of where a lawsuit has
been settled against the hair dye industry predicated on evidence
indicating that cancer was the result of using a hair dye?
Dr. CORBETT. As far as I am concerned, I'm certain that I have
never heard of one.
Mr. LENT. Mr. Hutt?
Mr. HUTT. I know of none.
Mr. LENT. I was handed a release this morning as I came into the
room from the Environmental Defense Fund wherein-and they are
going to testify later today so perhaps you will have the opportunity
to rebut what they may say, but they are announcing that a recent
study indicated that mice whose skin was painted with two permanent
hair dye preparations had a higher number of liver tumors than
animals that were not exposed to the dyes.
Can you tell us, Dr. Corbett, if you are familiar with this claim and
what your reaction to it is?
Dr. CORBETT. I read that this morning. I presume that they are
talking about a study that was carried by the industry, the final
results of which became available to me 2 weeks ago. I sent a copy of
the report to the committee staff. The conclusion of that report was
that there was no difference between the test groups and the control
groups. I have had the opportunity this morning to look quickly
through the ED]? testimony that is intended to be given this after-
noon. I notice that each time there is a citation of a higher level of
cancer on one of the test groups, as opposed to the control group, that
there are only one or two control groups mentioned. If my recollection
is correct, when we set up that study there were three control groups.
There were three common control groups. The results of all three
should have been stated if a fair evaluation were to be given.
I do~ not know who the EDF used as its expert in interpreting this
animal data, but he obviously comes to very different conclusions
frOm those of the people at the Eppley Research Institute in Nebraska
whom, as I understand it, are among the leading experts in interpre-
tation of animal data.
Mr. LENT. I have no further questions.
Mr. Moss. The Chair recognizes the gentleman from California,
Mr. Waxman.
PAGENO="0131"
125
Mr. WAXMAN. Thank you, Mr. Chairman.
Mr. Gore asked two questions. The second question was not
answered. His question was prefaced by a very serious charge that the
cosmetic industry lobbied Congress successfully for ~an exclusion for
coal tar hair dyes.
Can you explain to us why there is an exemption in the act and the
scientific justification for it?
Mr. MERRITT. Mr. Waxman, you are now talking about a legal
question. With the permission of the committee,. I would like to ask
Mr. Hutt to respond to that exemption and the implications of it. -
Mr. HUTT. Mr. Waxman, the origin of the exemption in section
601(a) for coal tar hair dyes arose because of lobbying not so much
by the cosmetic industry as by the beauty and barber groups in this
country. Their livelihood depended upon the use of coal tar hair dyes
for hair dye purposes.
They were concerned that there would be, in a regulatory agency,
insufficient recognition that coal tar hair dyes produce a low rate of
reaction among consumers and that if proper care is taken in deter-
ming whether a consumer reacts ahead of time that.rate of reaction
would be reduced still further or eliminated.
In short, they asked Congress to make in the law a benefit-risk
determination very similar to the' benefit-risk determination that this
committee of Congress and the entire Congress recently made with
regard to saccharin.. They said that they recognized that there will be a
low rate of reaction but that warnings and information to consumers
and a requirement for adequate testing of consumers before use of this
product should be sufficient to keep that to an acceptable minimum.
Mr. WAXMAN. I appreciate that answer and I find it fascinating.
What you are saying in effect is that the law `provides that the public
will be protected from poisonous or deleterious substances which may
render cosmetics injurious to users under the conditions of the use pre-
scribed in the labeling. Then, the law says that the provision protecting
the public from hazardous cosmetics will not apply to coal tar hair
dyes.
As I understand your testimony, the coal tar exemption was included
in the law as a result of lobbying, from the beautician industry-a
group whose livelihood was very much affected by Government
pressing too deeply into the safety of coal tar hair dyes.
Mr. HUTT. In my opinion the exemption probably was unnecessary
to achieve the intended purpose because I think that the Food and
Drug Administration would have recognized, as it does for niany other
consumer products, that a low rate of allergic reaction can be expected.
Nonetheless, that was the purpose of the Congress in putting it into
the act.
Mr. WAXMAN. Let me probe this a little bit with the testimony
given by Mr. Merritt. Here we have an example of an exemption put
into the law by a group that wanted to protect its economic interests.
The industry was afraid that if the law applied strict safety require-
ments to this particular kind of dye, then it would hurt the industry.
I want to say that I believe that the beautician industry was sincere
in thinking that there was probably a minimal risk. I also want to
say that I believe you are smcere' in thinking that there is probably
PAGENO="0132"
126
minimal risk in the kinds of dangers that the public might have in
using your products.
On the other hand, your testimony. implies that; "Even if there is
a risk, it's a societal issue and not a scientific issue."
"What is prudent action for one consumer is not acceptable to all
consumers." You also point out that: "The contributions of cosmetics
to self-assurance and self esteem are ~ts important as the nutritional
and medical benefits of foods and drugs."
What I'm trying to probe with you is this. I wonder whether your
sense of economic concern and the success of your industry is not
making you lean over pretty far to try to justify that maybe there is
no risk. As Members of Congress, we are charged with trying to look
out for the public interest-which includes the success of industries
in this country that do not produce products harmful to the public.
I wonder whether we ought to look at the assurances of your industry
with a certain amount of caution. We're talking about cancer. We are
talking about serious health risks. I am sure that you knowingly.
would not want to have people get cancer from your products. But
cancer is the result sometimes of not just one substance but the
combination of a number of carcinogens to which we are exposed in
our environment.
I would be interested in your response to that.
Also I want to point out one other thing before you answer. You
said you agreed with everything that Dr. Upton had to say. One
thing that Dr. Upton said very clearly was this. Whatever the regula-
tors might do, as a scientist he would urge people personnally not to
use dyes which contain chemicals the NCI finds to be carcinogenic.
I assume you do not agree with that.
Mr. MERRITT. Lt me take these in reverse order if I may. I have
never asked my wife or three daughters if they use hair colors and
they have never volunteered the information. But in all my contacts
with the industry scientists and sitting through the meetings I have
heard nothing that would cause me to recommend to my family that
they not use hair dyes if they so chose.
Mr. WAXMAN. But we have the head of the National Cancer Insti-
tute who says that he would recommend to his family, friends, and
others that they not use these hair dyes. He is a scientist. I assume
you are not a scientist.
Mr. MERRITT. I am not a scientist. I am an administrator. But I
am exercising that choice we believe the public should have. I believe
in my heart that they are safe enough that I would not recommend to
my family that they refrain from them, based on all the discussions
that I have been in. I have not been in all of them but I have been in
many of them.
Mr. WAXMAN. What is safe enough when 1 out of 4 people in this
country will get cancer? We have determined that 90 percent of
human cancers are caused by carcinogens that have been picked up in
the environment. We now find that there are carcinogens in some hair
dyes. How safe is it to expose people to that kind of risk? You talk
about the dangers of driving here in a storm. I assume you would want
your car to be in good order and the tires to be sufficient to carry
the car and to grip the road, and the brakes to be working. You would
PAGENO="0133"
127
not want to expose yourself to unnecessary, risks. Aren't we talking
about exposing the public to unnecessary risks?
Mr. MERRITT. Driving here this morning I rode' in a taxicab which
encountered several potholes. Even though the tires may have been
in good shape perhaps they might have damaged them for the next
passenger.
Mr. WAXMAN. You want government to fix those potholes?
Mr. GORE. That's a loaded question.
Mr. MERRITT. Thank goodness for a little levity this morning.
Let me say this. This is a very complex scientific issue. The `question
of the benefits and the potential risks, as I stated in my statement,
I believe should be referred to an organization similar to the National
Academy of Sciences and let them go into this entire safety question
and the risks involved.
You mentioned Dr. `Upton's statistics of 1 out of 4 perhaps getting
cancer. Mr. Gore referred to the number of those which come from the
environment. I happen to be a nonsmoker. But some of that environ-
ment in which I live is the exhaled smoke from others. I have the choice
of remaining with some of my friends who use tobacco or refraining
from being with them. I happen to choose' to continue to associate
with them.
I believe we should look at all the risks we face and I believe we
should make many judgments on all chemicals rather than indict a
single chemical ingredient based on one particular test.
Let's evaluate all the data. Let's make a balanced scientific judg-
ment. -
Mr~ WAXMAN. Do you think a balanced scientific judgment means
t'hat we have to prove in fact or beyond a reasonable doubt or with
a preponderance of'the evidence that there is a danger from chemicals
that are in the cosmetics? Or is it enough to have a suspicion that
would lead reasonable, expert, scientific opinion to conclude that there
is a real danger that hair dy~e consumers may increase their risk of
cancer? Cancer is not like a caustic, quick acting poison. Cancer has a
long latency period lasting 10, 20, or 30 years. This latency period
gives the public a false sense of security that there is nothing wrong
with using a substance because they don't get the deleterious re-
sults immediately.
Perhaps a chemical in these hair dyes will cause cancer 10 or 15 years.
later? Perhaps a chemical in these dyes will act in combination with
other substances to cause cancer.
Mr. MERRITT. I think you are getting into a very scientific issue
here. You are talking about presumptive risk versus potential risk.
Dr. Corbett, do you have any comment?
Mr. WAXMAN. I don't want a scientific explanation. I want to dis-
cuss the societal question that you posed. Are we willing to let society
take this kind of chance until we get scientific proof positive that the
danger exists? Or, at some point do we say that there is a risk sufficient
for us to be concerned and that we have to do something to protect
the public from this risk either by, No. 1, letting them know they are
taking this risk or, No. 2, in some circumstances removing the product
from the market when safer products could be substituted or when
the nature of the risk is unacceptable.
PAGENO="0134"
128
Mr. MERRITT. I believe that the decisions made should be made
reasonably and basically on the preponderance of examination of all
data and not on a single study.
Mr. Moss. The time of the gentleman has expired.
The Chair recognizes the gentleman from Pennsylvania, Mr. Marks.
Mr. MARKS. Thank you, Mr. Chairman.
Mr. Merritt, because ofi other appointments I will have to be leaving
soon and I will not have an opportunity to hear some of the other
testimony. But I would like to ask you if you could comment on some
statements that apparently will be made here this afternoon or later
this rnornin~.
I wonder if you might comment on the statements as we go through
it sentence-by-sentence and indicate if it in fact is true and if so what
your thoughts are about it.
The first statement is this, I am quoting. "As is true for other
cosmetic products, FDA has no statutory authority to require that
manufacturers test the products before they enter the marketplace."
Is that correct?
Mr. MERRITT. T would like to refer that to Mr. Hutt with your
permission. That is a legal question.
Mr. HVTT. Mr. Marks, that is untrue; The Food and Drug Admin-
istration has issued a regulation which requires, as the testimony
indicated, that all cosmetics be substantiated'for their safety prior to
their being marketed. A failure to do that would require a warning on
the front panel of the label of the cosmetic. It would be required to
state that the safety of the product has not been determined. Tech-
nically one could put out a product with that label on it. But as a
practical matter that regulation means that FDA is requiring the
product to be substantiated for safety prior to the marketing.
Mr. MARKS. Or stated that they haven't.
Mr. HUTT. Yes.
Mr. MARKS. But they don't have to be.
Mr. HUTT. They do not have to he but there is not to my knowledge
one cosmetic product marketed with that statement on it.
Mr. Moss. The Chair must acquaint the gentleman with the (act
that the rules of this House provide that if you read from a document,
you must identify it. I haven't the slightest idea what you are reading
from.
Mr. MARKS. I would be glad to, Mr. Chairman. I am sorry that I
did not before.
This is from the summary of the testimony that will be offered by
the Environmental Defense Fund before this committee.
Mr. Moss. Thank you.
Mr. MARKS. The second comment is:
A cosmetic producer does not violate the law even if it fails to conduct a single
safety test either before or after introducing a new product.
Is that correct?
Mr. IIUTT. The same answer I gave before would apply here,
Congressman Marks.
Mr. MARKS. I am quoting again: "Moreover, the FDA has no
authority to require the cosmetic manufacturers to provide the
necessary information that would enable the Agency to conduct its
own premarket evaluation."
PAGENO="0135"
129
Is your answer. the same?
`Mr. IIUTT. That is true. But I would go on to say that the industry
has, as Mr. Merritt testified a few moments ago, begun its own
program under which all of the published and unpublished scientific
information on safety of all cosmetic ingredients will be compiled
and made public as soon as they are compiled.
Mr. MARKS. The next statement:
Manufacturers cannot be compelled to submit ingredient lists, consumer com-
plaints or test data to the agency.
Is that correct?
Mr. HUTT. ~That is correct. That is, why the CTFA petitioned the
Agency for the three re~nlations governing voluntary submission of
information to FDA by industry.
Mr. MARKS. "Consumer products, such as hair dyes, sold for use
in beauty salons, do not even have' to `be labeled with the ingredients
they contain."~
Is that correct?
Mr. HUTT. That is correct. The Fair Packaging and Labeling Act,
under which ingredient labeling is required by FDA, applies only to
products sold at retail and not to other products.
Mr. MARKS. "Cosmetic manufacturers are not required to inform
the FDA that they or their products even exist."
Is that correct?
Mr. HIJTT. That is covered by the regulations governing voluntary
submission of information to FDA by industry. That is correct.
Mr~ MARKS. I want to ask you something.
In the opinion of the industry-and perhaps Mr. Merritt ought now
to answer this question-do you `not think that the FDA, under law,
ought to have the opportunity to have those things that I have just
mentioned that it does not already have? That is, without it being
voluntary.
Mr. MERRITT. Congressman,. we proposed a three-point voluntary
program which, number one, would ask manufacturers to register the
manufacturing facilities with FDA. Number two, ~tbey would submit
their formulations to the Food and' Drug Administration. And num-
ber three, it would provide regular reporting of product experience to
We have testified, and we'wouid not object if those three regulations
became mandatory.
Going one step further in Senate testimony 2 years ago, we testi-
fied that we would not object to a requirement of safety substantiation,
as outlined at that time, or if that data were required to~-be made
available to the Food and Drug Administration upon request.
Mr. MARKS. When was this voluntary request made of the industry,
that is, how long ago?
Mr. HUTT. Are you asking when the petitions were filed with the
Food and Drug Administration?
Mr. MARKS. Yes. ` .
Mr. HTJTP.. Approximately 1971, I believe.
Mr. MERRITT. It was 1970 and 1971.
Mr. HIJTT. I think they may have been over a 2-year period. I do
not recall.
PAGENO="0136"
130
* Mr. MARKS. In 1971 are you suggesting that you went to the indus-
try and asked them--
Mr. HUTT. We went to the FDA.
Mr. MARKS. Yes; with petitions. But you talk about voluntary
compliance with many of the matters that are not law at the present
time. I am asking you this.
Basically when did you first go to the industry and ask them to
voluntarily comply? When was that-about 6 years ago?
Mr. MERRITT. I would say it was 10 years ago when we started to
plan the whole program. Before an association can take an action, it
must determine the consensus of the industry. The industry supported
the voluntary proposals. We believe the data supplied to the Food
and Drug Administration provides a sound base on which the Food
and Drug Administration can take regulatory action.
Mr. MARKS. I am curious about this. How much of the industry
complied-100 percent; 90 percent; 80 percent?
Mr. MERRITT. Interestingly enough, in the Food and Drug Law
Institute Conference-I believe it was in early December-it was
reported that nearly 900 manufacturing establishments had registered.
The reference was made to the number of smokestacks which the
Food and Drug Administration had on its records. They revealed
about 20. percent of those were uncovered by the voluntary registra-
tion program of manufacturing facilities, which proves that the Food
and Drug Administration has gained substantial information from
this program.
Mr. MARKS. I think it also suggests that you are not answering my
question.
Mr. MERRITT. I apologize.
Mr. MARKS. You may not have understood. I am concerned about
your industry.
Mr. HtTTT. I think the information is contained on pages 6 and
7 of our testimony where it is stated that, for example, with
respect to registration with FDA, 900 client plants have registered.
That represents about 85 percent of the volume of cosmetics sold in
the United States. We have not attempted to break that down accord-
ing to the percent of volume of products sold by CTFA members.
Typically some smaller cosmetic companies are not members of the
association.
Mr. MARKS. What happened to those petitions you presented in
1971?
Mr. }IUTT. They were adopted by the Food and Drug Administra-
tion and they are currently regulations under which companies may
voluntarily submit the three types of information. They were promul-
gated by FDA as regulations and are in the Code of Federal Regula-
tions today.
Mr. MARKS. Are there any matters that I have mentioned here
under which the FDA does not have statutory authority? Would you
have any objection to their having statutory authority over these?
Mr. MERRITT. Are you referring to the questions that you read out?
Mr. MARKS. Yes. Let us start with the statutory authority to require
that. manufacturers test their products before they enter the market-
place.
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131
Do you have any objection to that?
Mr. MERRITT. I think we do, sir, because cosmetics are basically
safe. We believe there are so many similarities among. these products
that these products should be substantiated and evaluated prior to
marketing to determine whether a test is necessary.
To do that, the manufacturer must look at the chemical composition
and the ingredients and the purity of those ingredients and the stability
and the effect of their intermixing.
The exposure conditions must be looked at. The volume used in the
concentration and the rout of exposure and the frequency of adminis-
tration must be looked at.
The known data which is in the literature and in their files-
Mr. MARKS. Excuse me, Mr. Merritt. I am sorry to interrupt you.
My time is running out. I see the chairman with the gavel.
Answer me yes or no. Perhaps you have. You do object to the FDA
having statutory authority to require manufacturers to test their
products before they enter the marketplace; is that right?
Mr. HTJTT. But there is no CTFA objection to the requirement of
safety substantiation, which may be done on the basis of preexisting
information rather than new testing.
Mr. Moss. Excuse me. I think it might be helpful to permit the mem-
ber to secure answers to his questions. If you will kindly confine
yourself to very brief, concise answers, we would appreciate it. He
asked for a yes or no answer.
Mr. MARKS. Thank you, Mr. Chairman.
Mr. Moss. Please continue. I realize you have to ieave.
Mr. MARKS. I will take another moment.
Mr. MERRITT. Mr. Chairman, on quick perusal I believe we would
have no objections to the rest.
Mr. MARKS. You have no objection to a cosmetic producer conduct-
ing safety tests, either before or after iutroducing~ a new product; is
that right?
Mr. MERRITT. I said for the balance of the questions. First, I think
you make an evaluation of the product to determine if tests are neces-
sary. If so, you do the test to further substantiate the safety.
For the balance of the points here, I do not believe on a quick
perusal we would have any objection.
Mr. MARKS. Thank you very much.
Thank you, Mr. Chairman.
Mr. Moss. The Chair recognizes the gentleman from Ohio, Mr.
Luken.
Mr. LUKEN. If the chair would permit an attempt at levity, perhaps
your testimony might be characterized by some of the members as
similar to a statement made by "Mo" Udall at the Roast last night.
He stated that FDA has just banned births on the ground that
they will inevitably lead to death.
Would you make the argument, sir, that you, manufacturers of
hair dyes, would like to be in the same position that the tobacco
industry is in?
Mr. MERRITT. I am not sure I know about-
Mr. LUKEN. I am talking about without subsidies, of course.
Mr. MERRITT. Thank you for additional levity.
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132
I am not sure I know enough about the legal requirements for the
tobacco industry in their labeling. Perhaps Mr. Hutt might respond to
that iiicomparing the legal requirements here to the legal requirements
of the tobacco industry.
Mr. }IUTT. I am not sure, Mr. Luken, that I can answer that ques-
tion. I am not sure .of the precise intent of your question.
Mr. LUKEN. I think we have to look at the overall requirements. You
are certainly arguing fairness, I assume. I am trying to understand
the position here. There is an exemption in the law for hair dyes. Of
course, tobacco is not covered at all. It has a similar effect.
I just wondered if you see any distinction.
Mr. HUTT. The basic position of OTFA is that there is insufficient
evidence of risk to justify any kind of drastic regulatory action,
speqifically with respect to the hair dye ingredients that have been
tested by the NOT.
So, in that respect, I think the industry would say that it is not in
the same position as the tobacco industry.
Mr. LUKEN. Not as to the degree of risk?
Mr. JIUTT. Yes; as a factual matter.
But with regard to the issue of. consumer freedom of choice to
decide what risk to accept and what risks not to accept, the industry
believes that is a fundamental principle that should apply to these
products, as well indeed of all consumer products, as long as the risk
is just not outrageous, like poison.
Mr. LUKEN. Do you oppose the proposed labeling of FDA with
respect to hair dyes?
Mr. HTJTT. With respect to that proposal, the industry has not yet
filed its comments, Mr. Luken. I anticipate that it will take the
position that the factual evidence is, at this moment, insufficient to
justify a warning to consumers. If any of that information should be
given to consumers, it should be given in a more complete and bal-
anced way rather than through a single sentence warning.
There are many other consumer products that presently do not
bear warning that pose a much greater risk of cancer and a greater
risk to health `than do hair dyes.
Mr. LUKEN. One of the other members was pursuing that point
in a similar vein. But we agree, as I think Mr. Merritt agreed, that
the tests do show enough to indicate a presumptive risk, which we
described it as. Maybe that term does not really apply in its usual
sense because "presumptive" means pretty strong-but I took it by
your response that you did not really mean that it is a pretty strong
indication, but that there was just some presumption by reason of
the fact that these tests show that under certain circumstances, they
can be carcinogenic.
But with that presumptive risk present, can we tell the FDA that
they should not require labeling?
Mr.'~HUTT. I believe Dr. Upton, when `he referred to "presumptive
risk," said that what was then needed to determine whether there
was'a human risk, was to look at all the Qther available data and to
do additional testing.
The CTFA view is that until that further analysis is done-and
that is the term he used, "further analysis"-a warning would be
premature.
PAGENO="0139"
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Mr. LUKEN. Then you would not agree that the presumptive risk,
whose requirements have been met by the tests so far, is sufficient to
permit or require warning?.
Mr. HUTP. I believe the industry will file comments taking that
position, yes.
Mr. LUKEN. I think you know pretty well what the industry is
going to do.
Mr. HUTP. The difficulty we are faced with is this. We sit here as
an association. The association has not yet had an opportunity to
meet and decide on its views. That is why I have to speak somewhat
tentatively.
Mr. LUKEN. I might say that I have some sympathy with the
risk-benefit theorum that you espouse. But as to the requirements for
testing, I remain with some questions about that.
I think we all, on this panel, remain with questions about that.
Mr. HUTT. Mr. Luken, I think there was some confusion that was
raised. The cosmetic industry, as a whole, and the CTFA certainly
believe that the safety of any cosmetic should be evaluated and sub-
stantiated before that cosmetic is put on the market. We have never
said anything, to my knowledge, to the contrary.
Mr. LUKEN. Are we talking about voluntary?
Mr. HTJTT. Even mandatory. Even under law. CTFA has not op-
posed a legal requirement for safety substantiation.
What the industry is concerned about would be a law that would
require that every change in every cosmetic be required to be tested
in a way that would result in massive duplicative testing.
That is why when Mr. Marks raised the question: "Should every
cosmetic be tested before it goes on the market?", the answer was:
"Not necessarily, because there is so much testing of common ingredi-
ents which has gone on in the past that duplicative testing may not
be required for every product."
Mr. LUKEN. Are you not concerned especially abput the smali.busi-
ness members of your association as to the burdens that may be placed
on them if the industry is not able to test collectively, rather than by
individual firms?
Mr. HUTT. That is true. A cosmetic company might put out a new
lipstick and do nothing more than change 200 prior formulations in a
very small way. To require that each new product be subject to
duplicative testinj would be a waste of this country's toxicological
testing resources. As Dr. Upton said, they are in very, very short sup-
ply. We should use them where they are important.
But CTFA supports safety substantiation, without question, for
every cosmetic.
Mr. Moss. The, Chair recognizes the gentleman from California, Mr.
Waxman.
Mr. WAXMAN. I have some additional questions which I would like
to pursue with the witnesses,
I would like to know whether there are any benzidine-based dyes
currently in use by hair dye manufacturers?
Mr. MERRITT. Mr. Waxman, with your indulgence, I would clarify
one point you asked earlier.
Concerning Dr.. Upton's comments the other day, D~. Upton did
not urge others not to use hair dyes~ He said he would not use them,
PAGENO="0140"
134
but people should make their own decisions. That should be based on
all available facts.
Mr. WAXMAN. Let me interrupt you. I was there. I do not know what
information you have, but Dr. Upton indicated he was not a regula-
tor and that the decision as to whether hair dyes should be taken off
the market or whether a warning label ought to be required is a deci-
sion of a regulator. He is a scientist. From a scientific point of view,
he thought 4-MMPD was a sufficiently dangerous substance for him
not to want his family or others to use it. It is the decision of the
regulator, however, to decide whether it should be taken off the market.
But my question now to you is this: Are benzidine-based dyes
currently in use in hair dye products that are sold in this country?
Mr. MERRITT. I am not a scientist. I wonder at this point if I might
again call on Dr. Corbett who is intimately connected with this
subject.
Dr. CORBETT. The materials that you referred to as benzidine-based
dyes are dyestuffs which are made from benzidine. They do not
resemble benzidine in final form.
Mr. WAXMAN. Are they for sale as one of the constitutents of hair
dyes, which are sold freely today to the American people?
Mr. CORBETT. This question was asked of us about 3 weeks ago.
Mr. Moss. Dr. Corbett, you can answer that question. They are
or they are not. We do irot want a narrative wi.th each response. The
Chair wants to be very fair to you, but the Chair will also be fair to
the members of this panel. They are entitled to very concise responses.
That is all you have to give. We do not want the history.. We can
find that out from the staff.
Dr. CORBETT. I am sorry, Mr. Chairman. The answer, however,
cannOt be yes or no. There were three products which were manu-
factui~ed, as we understand it, up until sometime early or late last
year. They are still available, but are no longer being manufactured
in 1978.
Mr. WAXMAN. Why are they not being manufactured?
Dr. CORBETT. The manufacturer apparently dropped them from
the line.
Mr. WAXMAN. Do you know whether that was due to a conclusion
by the manufacturer that benzidine-based dyes were dangerous?
Dr. CORBETT. I have difficulty because it is not the company for
which I am employed. I am not privy to their reasons.
Mr. WAXMAN. Do you consider benzidine-derived dyes to be safe?
Dr. CORBETT. I consider them to be dangerous for ingestion be-
cause it is well known if they are ingested they will degrade to give
benzidine. However, they are high molecular weight materials which
probably would not diffuse through the skin. I do not know ior sure,
but when I look at the formula I think that they will not go through
the skin.
Mr. WAXMAN. Do you know for sure what they will not be absorbed
through the skin?
Dr. CORBETT. No, I do not. This is a guestimate based on what I
do know about which materials do go through the skin and which
do not.
Mr. WAXMAN. If they were absorbed, would you consider that
dangerous?
PAGENO="0141"
135
Dr. CORBETT. If they were, yes.
Mr. WAXMAN. Are you aware of the fact that the benzidine-
based dyes tested by NCI were found to produce tumors after 90 days?
The scientists at NCI found the results "striking" in producing
tumors after such a short period of time. They considered the dyes
to be potent carcinogens?
Dr. CORBETT. I think this is not a surprising result. It is consistent
with the results from feeding benzidine itself. But I would point out
that a recent paper by Dr. Bingham on the carcinogenicity of benzidine
suggests that it may be necessary to work in a benzidine plant for at
least 5 years before you run a real risk of getting bladder cancer from
exposure to benzidine.
Mr. WAXMAN. Is it your feeling that benzidine derived dyes are not
a danger because you do not believe they are absorbed through the
skin?
Dr. CoRBI~TT. I do not believe it is absorbed. If it were absorbed,
the quantities to which a human would be exposed would be miniscule.
As I said, Dr. Bingham's paper on followups of benzidine workers
suggested that quite a large exposure was needed before there was a
possibility of developing bladder cancer.
Mr. WAXMAN. It is your scientific opinion that there is a threshold
level for benzidine products?
Dr. CORBETT. You could ask that of each scientist and each
scientist will give you one or another answer. I think that the whole
data that exists on carcinogenicity can be fully explained on the basis
of a threshold theory.
Mr. WAXMAN. I see. So you think there is a threshold for benzidine
products?
Dr. CORBETT. I think there is. I think human experience shows
there must be.
Mr. WAXMAN. Human experience? What does that mean? You are
a scientist. You have looked at all the studies. Have you done studies
on human beings to come up with that conclusion?
Dr. CORBETT. Allow me to clarify one thing that was said a number
of times during this hearing on Monday, and repeated again today.
The impression has been given that 90 percent of human cancer,
being of environmental origin, is due to synthetie chemicals.
This is a totally wrong impression. In my mind it runs counter to
the war on cancer or to getting any success in it.
We heard testimony that cigarettes contribute to a large percentage,
diet contributes a large percentage, radiation contributes a significant
percentage, and ultraviolet light contributes a percentage.
All of these are environmental factors and are included in that 90
percent.
When you get to the bottom line, Dr. Ernst Wynder of the American
Health Foundation estimated that no more than 5 percent of human
* cancer is due ~o synthetic organic chemicals, as opposed to natural
Organic chemicals.
Mr. WAXMAN. You obviously can "out-science" talk me. But this
is a product [indicating] that one of my aides purchased off the shelf
in a retail establishment here in Washington, D.C.
It contains a chemical called "Direct Blue 6" which was the subject
of the recent NCI study. NOl found it to be highly carcinogenic. They
PAGENO="0142"
136
determined that there was a danger because "Direct Blue 6" may be
absorbed through the skin.
You told me that the industry is no longer manufacturing products
containing this chemical. Is that correct?
Dr. OOEEETT. That is what I understand, yes.
Mr. WAXMAN. Why don't you know why the industry has stopped
manufacturing hair dye products containing "Direct Blue 6"? Why
can't you tell us whether it is due to a recognition of the potential
health danger which you refuse to acknowledge?
Mr. MERRITT. I might interject, please.
Mr. Moss. Let us wait for the response.
Mr. WAXMAN. This is a scientist from the cosmetiô industry and I
want to find out why some of the members of the industry do not know
what Others are doing and why they have not voluntarily taken
benzidine-derived dyes off the market?
Dr. CORBETT. That is commercial information. I will try to find out.
I think it may be just prudent business sense that made them take it
off.
Mr. WAXMAN. I think it is prudent business sense not to put some-
thing on the market that contains benzidine-a substance we know is
clearly carcinogenic. I think we found out that this is a serious enough
matter that tumors were found in test animals after only 90 days.
NOT concluded these dyes were potent carcinogens and may well be
dangerous.
Then you tell me you do not even know why the industry took these
dyes off the market. This bottle of hair dye rinse was purchased within
the last couple of days. People right now are able to purchase products
containing benzidine.
Dr. OORBETT. With due respect, I am under oath and I do not know
the reason they took it off. I have not discussed it with them.
`Mr. WAXMAN. Are you aware of the fact that Japan banned ben~
zidine in 1971?
Dr. OORBETT. But this does not contain benzidine. It contains
disaso dyes that are derived from benzidine. They, in chemical char-
acter, are different from benzidine itself.
Mr. WAXMAN. They are derivatives, are they not?
Dr. CORBETT. Yes, but that is the same as saying aspirin is a benzi-
dine derivative. It does not mean anything.
Mr. WAXMAN. Did not NOT determine that benzidine-based dyes
convert to benzidine in the human body?
Dr. OORBETT. When ingested, yes.
Mr. WAXMAN. The question, then, is whether it is ingested.
Dr. CORBETT. I said that.
Mr. WAxMAN. Mr. Merritt, your testimony is:
To the vast majority of consumers, the contributions of cosmetics to self-assur-
ance and self-esteem are as important as the nutritional and medical benefits of
foods and drugs.
Are you telling us that it is as important, that is, that it is more
important to look good than to feel good?
Mr. MERRITT. T think looking good and feeling good perhaps could
be equally important to many people. On the other hand, there are
certain individuals to which one might be better than the other.
PAGENO="0143"
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Mr. WAXMAN. Really? I see. So, some individuals ought to have
cancer and others not?
~Mr. MERRITT. You are taking that out of context.
Mr. WAXMAN. I am disturbed by your willingness to make, the
evaluation that for some people it is so important to look good that
it is worth taking the risk that they are going to get cancer. I find
that appalling.
Is that what you are saying?
Mr. MERRITT. No, not m that context.
What about cigarettes?
Mr. WAXMAN. Aren't you just throwing some smoke up in the air?
Mr. Moss. With all due respect, we are not dealing with cigarettes
today. We have wrestled with that problem over a period of time in the
past. We will do it again, but not today.
Mr. WAXMAN. I also want to say something in relationship to ciga-
rettes. The fact that there are people who subject themselves to a
greater risk of cancer and heart disease by smoking cigarettes is no
excuse for allowing multi million-dollar industries to go ahead and
poison the American people with additional carcinogens.
I hope this is not something you would argue with.
Mr. Moss. The gentleman's time has expired.
The Chair recognizes' the gentleman from New York, Mr. Lent.
Mr. LENT. Thank you, Mr. Chairman.
Dr. Upton of the National Cancer Institute testified on Monday
that: The crux of the matter with respect td hair dyes is whether or
not there are so-called safe alternatives.
Can you' tell us whether there are any alternatives available in the
production of hair dyes that could avoid using the chemicals identified
by NCI as possibly cancer-causing?
Mr. MERRITT. I would have to defer to Dr. Corbett on that point.
Dr. CORBETT. It is possible to make hair dyes using a variety of
materials from amongst those which we currently use.
However, we find ourselves in a very difficult position at the
moment. The NCI has under. test some 10-and I am always differing
on this figure with members of your staff, Mr. Chairman-but there
are 10 hair dye ingredients and not 13 in the program.
But for some of these we do not have the results. For me to discuss
whether, based on legislation resulting from the NCI tests, we would
be able to continue manufacturing hair dyes or not, I think I would
have to say that we cannot tell until we know a~l of the data.
I could make a hair dye today that does not use 2, 4-diaminoanisole
or either of the two materials that are mentioned that were used in
hair dyes.
However, there are other dyes on this list that was up on the wall in
the hearing room on Monday for which we do not know the results
and without which I would be totally unable to make a permanent
hair colOr product. ,, `
We hoped that the NCI would be able to bring together and issue
at the same time all of the `reports on the hair dyes in the bioassay
program so that we can consider whether we can continue to manu-
facture the type of product that the American public is used to
without using the dyes found to be animal carcinogens by NCI.
PAGENO="0144"
138
But I have to come back again to the fact that I would prefer to
stay with materials on which we have 70 years of use experience,
with no apparent harm to the user or to those who `are professionally
exposed and a lot of animal testing.
Mr. LENT. `~ ou say you have had 70 years of experience of use of
these dyes without any. evidence of death, cancer, et cetera, ever
having been domonstrated.
Why is it, then, that the results of these massive animal feedings and
screening tests show cancer resulting in laboratory animals?
Dr. CORBETT. In the case of 2, 4-diaminoanisole, we have a situation
which may well be something which no one would have suspected,
namely, that the material is a thyroid stimulant, or thyroid-depressing
agent, as well as being useful for a hair dye. It is being fed at such a
level that it upsets the hormonal balance of the animal and produces
physical deposits in the thyroid. That results in secondary cancer.
This is a very strong possibility in view of the results.
This is why we question the validity of that test in determining
that 2, 4-diaminoanisole is a chemical carcinogen.
Mr. LENT. This is strangely reminiscent of the saccharin coritro-
versy where the Canadian rats were fed the massive doses of saccharin.
Certain conclusions were drawn from that.
There is an important difference here in that human beings do not
ordinarily ingest hair dyes, whereas they do saccharin. So, it would
seem to me just on a very superficial level that the case that has been
presented against the hair dyes is substantially weaker than was
presented against saccharin.
Someone said that there were 34 or 38 million people in this
country who use hair dyes. Is that correct?
Dr. COEBETT. It s.ounds like a reasonable figure.
Mr. LENT. What percentage of them, do you estimate, are women,
and what percentage are men?
Dr. CORBETT. Men have always been a little reticent to admit to
this. We have never really had good figures. I have always guessed
that probably 80 to 90 percent of these users are women.
Mr. LENT. Where do we find the greatest incidence of cancer with
respect to sex as between men and women? Do women have the
greatest incidence, or men?
Dr. CORBETT. Men.
Mr. LENT. So, men have the greatest incidence of cancer in this
country, notwithstanding the fact that 80 to 90 percent of the users
of hair dyes are females; `is that right?
Dr. CORBETT. That is correct.
Mr. LENT. What kind of conclusion could a scientist draw from
that? That is a large sampling, I am sure.
Dr. COEBETT. Scientists are very reticent to draw absolute conclu-
sions on that sort of data, but I do find it comforting to recognize
that 10 percent of American women were using hair dyes 25 years
ago.
During the subsequent 25 years, there has been a decrease in most
forms of female cancer, as attested to by the American Cancer Society
and by agencies of the Federal Government when testifying before
Congress.
PAGENO="0145"
139
On this basis I think a priori there seems to be no risk. I would
want more detailed studies.
You mentioned saccharin. I notice in this morning's New York
Times that the National Cancer Institute and FDA have announced
they are going to jointly carry out an epidemiology study on 9,000
people for 18 months in 9 States to determine whether saccharin
causes bladder cancer.
I would welcome such a study for hair dyes. In fact, the National
Cancer Institute, the hair color industry, and the Environmental
Defense Fund had the first meeting of a. joint scientific committee
last week, at which time we told the other two representative groups
that we were trying to evaluate what sort of epidemiology is required
on top of what we already have.
Mr. LENT. Have there ever been any tests conducted with labora-
tory animals wherein instead of feeding the dye to them, they put it
on their skin or on their coats?
Dr. CORBETT. Yes..
Mr. LENT. Have these types of tests ever been carried out with
respect to laboratory animals?
Dr. CORBETT. This is exactly the type of testing that the industry
has done in its safety evaluation programs, starting over 10 years ago.
The technique is to apply the hair dyes to the clipped skin of rats
and mice and to leave the material in contact with the skin indefi-
nitely rather than to wash it off, and to do this as frequently as phys-
ically possible.
This way we believe we get an exaggeration of about 300-fold over
human experience. After doing this for the whole lifetime, in the case
of five groups of animals that have been completed already with
2,4-diaminoanisole, we have never elicited any response. A total of
900 animals have been studied.
Mr. LENT. You had a control group that you put something else
on their coat and you had a test group that you applied hair dye to?.
Dr. CORBETT. We put on a hair dye mixture simulating the product
use by women.
Mr. LENT. Have the results of these tests ever been turned over
to the NCI?
Dr. COREETT. Not as yet because they have yet to discuss the
results on hair dyes at their clearinghouse. We have been compiling
information to submit to members of the clearinghouse sometime
during February for them to consider our data alongside the Insti-
tute's data.
Mr. LENT. Thank you, Mr. Chairman.
Mr. Moss. The Chair recognizes the gentleman from Tennessee,
Mr. Gore.
Mr. GORE. Thank you, Mr. Chairman.
Mr. Merritt, you said in your testimony that you support the
removal of nitrosamines from cosmetics. Does that constitute a
recognition that they are hazardous?
Mr. MERRITT. This constitutes a recognition of nitrosamines as a
contaminant in cosmetics, yes. It is a possible contaminant.
Mr. GORE. There are lots and lots of products that have nitros-
amines. There is a lengthy list. Reading over this list1 I recognize
lots of common products.
24-600 0 - 78 - 60
PAGENO="0146"
140
How can it be removed if the Government has no authority to do
it?
Mr. MERRITT. Would you repeat the question?
Mr. GORE. Are you proposing a voluntary removal of nitrosamines?
Dr. CORBETT. No, we are not proposing only a voluntary removal.
I would like to ask Dr. Estrin, who is our scientific vice president,
and who has been working on the subject, with our industry task
force since last summer, to respond.
Mr. GORE. I do not want a long medical response on it. I want to
know"whether you wo~ild recommend Government authority to have
the removal of nitrosamines from cosmetic products.
Mr. MERRITT. I would think they have the authority now under the
present Federal Food, Drug, and Cosmetic Act.
Mr. GORE. If they do not, you would recommend that they would
have it?
Mr. MERRITT. I think they do have it now.
Mr. GORE. All right.
What if it is not a contaminant, but part of,' the product itself,
an ingredient? Let us say it is formed from the interaction of the
ingredients. Then how do you deal with it?
Mr. MERRITT. There again, I am not a scientist. I would have to
defer to Dr. Estrin on how you deal with the' scientific interaction
of the chemicals. /
But .1 will tell you that our goal is to reduce the level of that con~
taminant to its absolute lowest possible level.
Mr. GORE. Why?
Mr. MERRITT. Basically that is our policy with respect to every
undesired chemical.
Mr. GORE. Why is it undesirable? Why do you not want it in there?
Mr. MERRITT. Because we want to produce the safest possible
product under any circumstance.
Mr. GORE. It is not safe?
Mr. MERRITT. I am assuming from your comment that it is not
safe. I am telling you that it is our policy and our goal--
Mr. GORE. Would you make the same assumption o~i other ingre-
dients if I mentioned them and institute a program to remove them
also?
Mr. MERRITT. If you can get rid of them and still have a product,
yes.
Mr. GORE. Suppose you cannot get rid of them? Suppose they
cause cancer, then what?
Mr. MERRITT. We are right back to a benefit-risk analysis, with the
consumer making a judgment based on knowledge of the risk and all
the data.
Mr. GORE. Are you willing to accept the proposition that nitrosa-
mines cause cancer?
Mr. MERRITT. I am not willing to accept it. On the basis of not
being a scientist, I have to-
Mr. GORE. I would like a brief answer, then I would like to get it
from your scientific team there.
Mr. ESTRIN. Many nitrosamines do cause cancer in animals. There
is no evidence that they cause cancer in human beings.
PAGENO="0147"
141
Mr. GORE. Then we are back at the animal-human juncture. Is
it not true that the scientific community pretty well recognizes the
validity of animahtesting, however, for carcinogenicity?
Mr. ESTRIN. I have a paper before me by Dr. Tennenbaum on
environmental nitroso compounds and their implications for public
health.
I do not want to read the whole paragraph, but it says in conclusion:
It has to be said at the outset that it is exceedingly difficult, on the basis of
present knowledge, and a definitive conclusion cannot be reached at this time.
He is referring to the possible implications for man for these animal
carcinogenicity tests~
Mr. GORE. To your knowledge, how many times has the scientific
community found a substance that causes cancer in humans that
does not cause it in animals?
Mr. ESTRIN. I have no information ab6ut that.
Dr. CORBETT. Arsenic and apparently benzene. This was testi-
mony from Monday. I remember that.
Mr. GORE. So of all the substances known to be carcinogenic,
there are only two that have found to be carcinogenic in humans and
not in animals?
Dr. CORBETT. There are only 30 compounds known to be carcino-
genic in man, so ont of all the substances there are only two.
Mr. GORE. Would that indicate to you that there is some validity
to animal testing?
Dr. CORBETT. It does not at all.
Mr. Moss. Would the gentleman yield to the Chair for a moment?
Mr. GORE. Certainly.
Mr. Moss. If there is no validjty to animal testing, then why do
you, in your laboratories, undertake to use animals for testing
purposes?
Are you engaged in a useless exercise.
Dr. CORBETT. Mr. Chairman, with respect to your asking me to
try to be brief-and you have forced me in that position-
Mr. Moss. I have not forced `you in that position. I have asked
you to be brief, but not to the point where you could not respond, but
not to give narratives.
Dr. CORBETT. I did not `mean to imply that there was no validity
in animal testing. `
Mr. Moss. Now we have a qualification. There is validity to anima1
testing, then?
Dr. CORBETT. Yes.
Mr. Moss. Is there total validity to any testing?
Dr. CORBETT. Not' in animals, no.
Mr. Moss. In any of the testing that you do, is there total validity
to any of it?
Dr. CORBETT~ It depends on what you state the objective to be in
the first place.
Mr. Moss. Do you have a total objective?
Dr. CORBETT. Yes.
Mr. Moss~ Do you have total validity to the testing, then?
Dr. CORBETT. If we set in our test the objective to demonstrate, as
far as possible, by means which represent the route of human exposure,
that certain materials are safe, then those tests are as valid as possible.
PAGENO="0148"
142
Mr. Moss. You remind me of a story about the late Senator from
Tennessee, Estes Kefauver, who said that he would like to have a one-
handed scientist because everytime he talked with them, he heard them
say: "But on the other hand."
As a result, anything they told him was equivocal and somewhat
meaningless. I am afraid that is what we are hearing here.
Mr. GORE. You say you know some one-handed lawyers?
Dr. COREETT. Yes.
Mr. Moss. The Chair does not fall into the category of being a
lawyer.
Mr. GORE. Nor do I, Mr. Chairman, I hasten to add. I have heard
of one-handed Congressmen, though.
To be realistic about it, there scarcely has ever been a substance
that has been found to be carcinogenic in every known species of
animals, like nitrosamines, which do not show up to be carcinogenic.
Let us be realistic about it.
You have said there are only 30 known human carcinogens. Some
of the~ are in hair dyes. That is what we are talking about.
You~ have benzidine, for example.
If you are willing to accept the validity of animal studies for nitro-
samines, then it seems inconsistent to turn right around and say that
you are not willing to accept the validity of those tests for other sub-
stances that we are talking about here.
It seems inconsistent to me.
If you would like to comment, go ahead, and then I will yield to
my colleague from New Jersey.
Dr. CORBETT. I thinkI have to mention one thing here with regard
to animal tests that show human carcinogenicity. Dr. John Weisburger,
who actually started the NCI program, was telling me that in the
next edition of his book he is going to write up an observation which
he has recently made, that when one finds those compounds which
are known human carcinogens and then tests them in animals, that
the effects are quite dramatic.
We mentioned one here this morning with regard to benzidine.
You get 100 percent of cancers in the animals in a very short period
of time.
The things we have seen coming out of the NCI bioassay program
with respect to hair dyes have not been that sort of results at all.
They have been totally different types of results with four or five
tumors here and massive thyroid tumors in the case of 2,4-
diaminoanisole, and not at all consistent with the type of results
that one got with human carcinogens.
I must unload the premise that we have some of these human
carcinogens in hair dyes. That is n&t true.
Mr. GORE. What about this [indicating]?
Dr. CORBETT. That has not been proved a human carcinogen other
than by oral route.
Mr. GORE. It is benzidine. It is on the list. There are 36 here. One
of them is in this [indicating]. .
Dr. CORBETT. That contains a. compound derived from benzidine.
Mr. GORE. It contains a benzidine derivative which you,
Dr. Corbett, have testified is converted into benzidine in the human
body.
PAGENO="0149"
143
Dr. CORBETT. If it gets into the human body.
Mr. GORE. Are hair dyes absorbent? They are designed to he
absorbent; right?
Dr. CORBETT. That product is a temporary product which is
designed to paint on the surface of the hair.
Mr. GORE. Does the human body absorbe hair dyes?
Dr. CORBETT. There are three classes of hair dyes: permanent,
semipermanent, and temporary.
Mr. GORE. Does the human body absorb all of them?
Dr. CORBETT. No, not as far as we know. Permanent and semi-
permanent can be absorbed, yes, but temporary is not even designed
to penetrate into the hair fibers. It is designed to stay on the surface.
Mr. GORE. Do you know for certain that the others are not ab-
sorbed by the human body?
Dr. CORBETT. It is my scientific judgment, but I do not know for
certain. I think those dyes are too large to go into the human body
through the skin.
Mr. Moss. The time of the gentleman has expired.
The Chair recognizes the gentleman from New Jersey, Mr. Maguire.
Mr. Moss. I am sorry; Mr. Rinaldo.
Mr. RINALDO. Mr. Merritt, on page 1 of your statement you say
that the cosmetic industry accounts for about $9 billion of retail
sales in the United States annually.
Could you give us a rough idea of how much the industry spends
on testing its products before marketing?
Mr. MERRITT. We have no idea. We do not collect any statistics
of that sort-that is, any operating ratio figures-because of possible
antitrust implications.
Mr. RINALDO. You could not give us any percentage?
Mr. MERRITT. We do not have any figures of that sort.
Mr. RINALDO. Do you perform more tests before marketing as
opposed to after marketing?
Mr. MERRITT. I would assume so. I would be virtually positive in
every case that that would be true.
Mr. RINALDO. What percentage of tests are performed prior to
marketing a product as opposed to after a product is already on the
market?
Mr. MERRITT. I have no idea, but we could try to get those figures
for you.
Mr. RINALDO. Can you tell me whether or not the tests you do per-
form are the same kinds of tests that the NCI performs?
Mr. MERRITT. I would assume, in some cases, that the tests would.
be the same as those conducted by NCI. However, I could not say
and do not know with respect to many categories.
Mr. RINALDO. Could you tell us in what areas or in what respect the
tests are different than the tests performed by NCI.
Mr. MERRITT. I think the NCI test is designed to screen those
chemicals, which by their chemical structure, appear t~ be most likely
to cause cancer. We are looking at finished products.
Mr. RINALDO. It is my understanding from testimony, and from my
knowledge of the subject matter, that when we talk about pretesting,
it is defined differently than premarket approval. They are two
different actual topics.
PAGENO="0150"
144
What effect would the premarket approval have on your industry, if
any?
Mr. MERRITT. I think it could have a very severe effect on industry,
as well as on the entire scientific community in its goals to find solutions
to other problems. For premarket testing, Arthur D. Little did a
survey for us 2 years ago in whjch they numbered the literally millions
of animals and slides which would have to be reviewed by pathologists
if this were required for the products on the market. The cost of the
tests at that time would exceed the annual sales of the industry.
It would take 30 years to complete that.
Mr. Moss. If the gentleman will yield, could you supply that study
for this record?
Mr. MERRITT. We will supply that study for the record.
Mr. Moss. Thank you.
Without objection, that will be inserted into the record at this point.
The results and the study.
Mr. MERRITT. Yes, we will.
[Testimony resumes on p. 179.]
[The following material requested was received for the record.]
PAGENO="0151"
145
DRAYf REPORT TO THE
* LEGISLATIVE PLANNING GROUP Or~1~K
I- S1Th~RY AND C0NCLUSIOI~
* Puhdamental characteristics of the cosmetic and toiletries
industry are the large number of different products that it produces and
offers for sale at any given time, and the annual rate of introduction of
new products. A conservative estimate of the number of products mow
available to retail outlets is about 25,500. According to the proposed
Eagleton Bill (S.863), testing of all of these existing products would
have to be completed within two and one-half years from the date of
enactment of the legislation.
Using the conservative number of 25,500 cosmetic products and
ingredients outlined in this report, the minimum total number of animals
required for the testing program proposed in the Eagleton Bill would be
38,154,000 rats, 60,879,000 mice, 6,826,000 rabbits, 504,000 dogs, and
96,000 guinea pigs. This requirement, in addition to animals needed
for studies in other programs would severely tax the present animal
breeding facil~ties. Por some products, the monkey might be the pi~e-
f erred species, particularly for inhalation tests, and the number in-
volved would probably necessitate expansfon of breeding facilities since
most of the primates now used in research are imported and are currently
in short supply.
The total. cost of the testing program, if conducted on the
estimated 25,500 products and ingredients, would appear to be at least
$6,625,450,000. While the cost is not the limiting factor, it is worthy
of consideration.
Using the test methods described in the report, it ~iould
require about 30 years to complete the program as outlined in the
Eagleton Bill * One of the pr~.mary limiting factors is the small number
of qualified pathologists (1,340) estimated to be currently available
for evaluations of the 1,070,000,000 or so slides which would be produced.
76302
February 8, 1974
Arthur 1) Little Inc
PAGENO="0152"
146
We assume that additional pathologists and other scientists wo~ild be added
to the work force each year, but new products requiring similar testing
will also be introduced. We understand that the overall number of
cosmetic products has been increasing each year by perhaps 10%.
Data collected strongly indicate that the laboratory facilities
currently available for the required safety testing are inadequate to
complete the studies in a time period near the two and one-half years
required in th~e Eagleton Bill.
The severe research impact of the requirements of the Eagleton
Bill can be readily illustratrd if one assumes the utilization of all
of the estimated 1,340 experimental and veterinary pathologists on a
half-time basis. With this restriction one might evaluate about 2,000
products in the required two and one-half year period. (John A. Wenninger
n the Food Drug and Cosmetic Law Journal, April 1972, pg. 213, reports
."one of the larger costnet~Lc manufacturers.. .produces over 2,000 sep-
arate cosmetic products, exclusive of shade variations, and introduces
about 50 new pioducts each year.") The effect of testing the 2,000
products, which is~ less than 10% of those currently on the market, would
by this estimate have a strong and adverse impact on such major research
programs as the testing of new drugs, food additives, agricultural and
industrial chemicals and chemotherapeutic agents which must compete for
the same facilities and ~ersonne1.
The need for insuring the safety of products to be used by man
is clear. However, it also is obvious that priorities must be assigned
to ensure the most appropriate utilization of our research facilities
and our scientific personnel.
PAGENO="0153"
147
test animals or subjects, (3) the approximate duration of the test, and
(4) the estimated cost of the test. The results of these analyses are
shown in Table IV.
For this study we also sought and obtained quantitative infor-
* nation relating to the number of independent and captive industrial
facilities capable of carrying out safety testing, and the number of
toxicologists, pharmacologists, and experimental and veterinary patholo-
gists availab)~e to supervise and execute such tests. We also conducted
interviews with personnel at the National Cancer Institute to ascertain
the rate of build-up of their program and of their facilities for
screening various materials for carcinogenic activity. We were especially
interested in the number of chemicals which the NCI had under test during
the fiscal year 1973, and in the rate of introduction of new chemicals
into their testing program.
Since the level of- the testing effort recommended in the pro-
posed Eagletbn bill, 5.863, will be largely determined by the number of
cosmetic products and ingredients to be tested, at the very start of
this program we attempted to obtain a reliable measure of the number of
these products in "commercial distribution." We started by preparing a
list of companies engaged in the manufacture of cosmetic and toiletries
products and ingredients (see attachment). While this program was under
way, we learned that the CTPA had sent out questionnaires to approximately
750 cosmetic and toiletries manufacturers requesting information on the
number of products they had in "commercial distribution," as well as the
number of new products they had introduced during the past year. Of the
questionnaires sent out, 196 replies were returned. Only the information
obtained from the questionnaires, as well as from the ingredients listed
in the CTFA Cosmetic Ingredient Dictionary, 1973, ~First Edition, published
by the Cosmetic, Toiletry, and Fragrance Association, was used to deter-
mine the number of products and ingredients to be tested. We felt that
any figures obtained by an extrapolation of these data could prove
unreliable and that it was therefore wiser to use omly the documented
numbers.
PAGENO="0154"
148
III - ECONOMIC CHARACTERIZATION OF THE INDUSTRY
This section presents some of the most significant aspects of
the economic picture of the cosmetic and toiletries industry. For the
purposes of this discussion, economics involves estimates of the number
of companies engaged in the manufacture of cosmetic and toiletries products,
the dollar value of sales, both at the manufacturers' and the retail
level, the most active companies in the industry, retail sales for the
various categories of products made and sold by the industry, and the
average rate of growth of retail sales of toiletries and cosmetic
products. In Section IV we shall consider. the number of products in
"commercial distribution" and the rate of introduction of new products on
a~per annum basis.
While' it is estimated that about thirty companies account for
about 85. percent of total in~Iustry sales at the manufacturers' level,
many companies contribute to the remaining 15 percent. The estimaeed
number of firms in the entire industry, is difficult to ascertain, and our
current estimate is about 1785. (See appended document.)
The U.S. Department of Commerce reports that industry sales at
the manufacturers' level amounted to $4.24 billion in 1972. Measured at
the retail level, industry sales for 1972 are reported as $5.3 billion.
Table `I pres~nts the retail sales of cosmetrc and toiletries products
for the years 1965 to 1972. Table II lists representative companies
according to volume of cosmetic and toiletries sales ranging from $10 million
per year to over $500 million per year.
An examination of the rate of change of the, retail sales reported
for the industry over the past few years indicates the rate of growth for
the cosmetic segment of the industry to be about 10 percent per anrnnn,
and that for toiletries, approximately 7 percent per annum. It should be
noted that material shortages now experienced in many other industries
will probably adversely affect the rate of growth of the cosmetic and
toiletries industry, at `least over the next year.
In addition to the above information, we have presented in
Table III retail sales reported in terms of various product categories.
PAGENO="0155"
149
TABLE I - RETAIL SALES OF COSMETICS & TOILETRIES
1965-1972
Retail Sales ($000,000)
Cosmetics Toiletries Total
1965 1,062 - 2462 3,224
1966 1,169 2,389 3,558
1967 1,243 2,551 3,794
1968 1,359 2,725 4,084 -
1969 1,457 2,931 4,388,
1970 1,573 3,145 4,71k
1971 1,695 3,394 5,089
1972 1,815 3,509 5,314
Source: ~~g~Trade News 1965-1970, Product Management (October, 1973),
and Arthur D. Little, Inc. Estimates
PAGENO="0156"
TABLE II - COMPANIES ACTIVE IN COSMETICS AND TOILETRIES, 1972
Total C&T Sales as I of Total
Corporate Sales Corporate Sales C&T Sales I Domestic C.T.
(MN$) (MM$)
100% 1005 70%
337.E 640E 50%
Sub Totals 1645
35% 420 95%
* ~panz
Over $500 Million
Avon Products, Inc.
Colgate-Palmolive Co.
Helena Rubinstein &
toiletries
Over $200 Million
Bristol-Myers Co.
* Clairol, B-M Products,
Luzier
The Procter & Gamble Co.
Revlon, Inc.
Johnson & Johnson Corp.
The Gillette Co.
Personal Care Division
* Toiletries Division
American Cyanamid Co.
John H. Breck Inc., Shulton
Norton Simon Inc.
Max Factor & Co.
1005.3
1905.9
1201.2
3514.4
438.6
1317.7
870.5
U.S. C&T Sales
(NM $)
700
320E
400
10%
77%
350
336
67%
70%
*
235
235
* 28%
370
*
70%
260
38%
330
50%
165
70%
*
161
40%
80
1358.9
17%
230E
1385.3
14% -*
200E
Sub Totals *~3*~
1536
PAGENO="0157"
* Total C&T Sales as I of Total
~~pany ~q~p1orate Sales Corporate.Sales C&T Sales I Domestic C.T. U.S. C&T Sales
(MM $) (~4j( 5) (~g~ $)
* 5100-200 Million
Alberto-Culver Co. 182.7 93% 170 83% * 142
Chesebrough-Pond's Inc. 350.8 46% 162 50% 81
Ponds, Prix~ce MatchabeUi,
ICC
Paberge, Inc. 145.1 87% * 126E 90% 113
Rayette, Faberge, Polly
Bergen
* Pfizer, Inc. 1093.4 11% l2OE 75% 90
Leeming/Pacquin Division,
* Coty
The Mennen Co. 100.0 100ZE 100
* Estee Lauder Inc.. 100.OE 100ZE * ~ 100
Squibb Corporation 769.5 13% 100 85% 85
Lanvin - Charles of the
Ritz Line
Sub Totals 878 * * 511+
550-100 Million
Schering-Plough Corp. 504.2 19%. 95 80% 76
Maybelline Co., * * *
Coppertone Corp.
* Lever Brothers Company * * 75E 100% 75E
Eli Lilly & Company 819.7 9% 76 29% . 22
Elizabeth Arden Sales Corp. .* * *
Helene Curtis Industries, Inc. 59.3 * 100% 59 83% 49
PAGENO="0158"
Total C&TSale.s as % of Total
~~pany~ Corporate Sales Corporate Sales C&T Sales %_Domestic C.T. U.S. C&T Sales
(MM$) (NM$) (1*I$)
American Brands 2998.9 1.8% 53 83% 44
The Andrew Jergens Co.
Noxéll Corp. 83.5 93% 78 83% 64
Sub Totals 436 329
$20-50 Million
Bonne Bell Inc. 30.0 100% 30 100% 30
Smith Kline & Trench Labs. 402.3 7% 28 100% * 28
Love Cosmetics, Sea & Ski
Merle Norman Cosmetics Inc. 28 100% 28 * 100% . 28
MEM Company Inc. 28 100% 28 100% 28
English Leather, Capucci
DART Industries 888 3% 27 50% 14
(Vanda - Beauty Counselor) *
$lO-20 Million
Johnson Prodt~cts Co.,.Inc. 17.6 100% 17.6 100% 17.6
The Nestle-Lemur Co.. 10.1 100% 10.1 100% 10.1
Sources: Product Management (September 1973), Fortune (October 1973), Dun & Bradstreet Inc., Conpany
Annual Reports, Arthur D. Little, Inc. Estimates
PAGENO="0159"
TABLE III - RETAIL SALES THROUGH ALL OUTLETS OF MAJOR CATEGORIES
OF COSMETICS & TOILETRIES 1965, 1970, 1972
Hair Preparations
Makeup Preparations
Oral Hygiene Products
Men's Toiletries
External Persona]. Deodorants
Fragrances
Toilet Soaps
Face Creams
Hand Preparations
Misc. md. Suntan Preparations
Total
17 859 16
14 763 14
11. 566 11
.9 466 ~9
8 448 8
7 366 7
4
4
3
1965 1970 1972
Category $MM Z of Total $MM Zof Total $T'IM
Zof Total
23 l;262 24
24
17
14
12
5.
7
9
1,083
803
661
521
430
380
333
771
540
465
374
176
236
299
154
132
77
5~ 217 239
4 174 4 198
2 116 2 147
3,224 iOO 4,718 100 5,314 100
Sources: Drug Trade News, Product Management, and Arthur D. Little, Inc. Estimates
PAGENO="0160"
154
To determine the number of ingredients, we counted the materials
listed by chemical nameçin~ the CTI?A Cosmeti redip~iOflar1~4 and
obtained a total of l,52l.~ When we attempted to obtain an estimate of
the number ot fragrances and commercially available components used for
formulating fragrances for this purpose, we contacted several fragrance
industry representatives. They were, however, unable to supply actual
numbers and, instead, suggested a method they believed to be reasonable
for estimating the number of Fragrances sold: by taking somewhere
between 5 percent to 15 percent less than the number of individual cos-
metic and toiletries product entities, we can obtain an estimate of the
number of fragrances. If we assume that 85 percent'of the number of
products reported' by the 197 companies responding to the CTFA question-
naire had di~fe~ent fragrances, the estimated number of fragrances
amounts to 2l,~00. -
For estimating the extent of safety testing required under the pro-
posed Eagleton legislation, we employed the number 25,500 products and in-
gredients. We believe this to be a very conservative base, for the following
.reasons
(1) The totkl number of cosmetic prociucts obtained from' the
responses to the questionnaire sent by the ~TFA were gained from
197 companies, or 26 percent of thope queried. Furthermore, we estimate
(see attachment) that the number of firms in the industry exceeds 1,700.
Thus, the product number is based on a small percentage of the firms
that comprise this industry. While many of the companies that did
respond are the larger manufacturers and therefore account' for a larger
percentage of the ~5roducts than their number indicates, it is clear that
there are many more than the 25,500 cosmetic products and ingredients
produced and sold by the industry.
PAGENO="0161"
155
(2) The product number base, 25,500, does not include almost
1,000 ingredients listed in the CTPA Dictionary4 under their chemical
names. The figure also does not take into account the fact that, whi],e
1,521 materials are listed by chemical name, many of these compounds
are made by more than one manufacturer and are not identical in all
chemical and physical properties. If the ingredients are counted on
the basis of trade names, the number obtained would be 4,968. This
estimate of 25,500 compounds and ingredients does nçt include irigredi~nts
listed by trade name.
(3) Neither the number of fragrances nor commercially
available components used for'forinulating fragrances are included in
the 25,500 figure. As indicated above, by one method of estimation,
the number of fragrances sold to the cosmetic and toiletries companies
that responded to the CTFA questionnaire would amount to 21,000.
(4). It' is also important to note that one of the distinguish-
ing characteristics of the cosmetic and toiletries industry is the, rate
at which new products are introduced into the market. As stated `above,
almost 4,000 new products were introduced last year by the 197 companies
responding to the CTFA questionnaire. We have not considered this
factor in our discussion on safety testing, presented in a later section
of this report.
We recogniI~ that many cosmetic and toiletries products and
ingredients that are n'bw offered for sale have been subjected to `some
safety testing, though it is generally of a short-term nature. We
have considered this fact in our study.
24.600 0 - 78 - 11
PAGENO="0162"
156
SOURCES
1, S.863, Cosmetic Safety Act of 1973, Introduced February 15, 1973:
Sec. 103(b). A proposal, to amend the Federal Food, Drug and
Cosmetic Act: Sec. 201(i).
2. The American Heritage Dictionary of the English Language, pub-
lished by American Heritage Publishing Co., Inc. A Houghton
}lifflin Company, 1973 Edition.
3. S.863, Cosz~etic Safety Act of 1973, Introduced February 15, 1973:
Sec. 201. A proposal to amend the Federal Food, Drug and
Cosmetic Act: Sec. 201.
4. CTFA Cosmetic Ingredient plctionary, 1973, First Edition, pub-
lished by the Cosmetic, Toiletry and Fragrance Association.
PAGENO="0163"
157
V.- DESCRIPTION AND BRIEF DISCUSSION OF TESTS FOR PRO~~~
SAFETY REQ~RED BY THE EAGLETON BLL
The following description o~ tests required asa minimum by
the Eagleton Bill should be considered only as guidelines and not as
firm requirements of a particular agency, administration or department.
In fact, opinions of many scientists are known to differ somewhat, not
only as to the~number and type of animals to be employed, by what route,
and how long they should be dosed and subsequently observed, but even
which is the most appropriate test method. It is generally agreed, how-
ever, that testing protocols should be flexible enough to accommodate
products with different pharmaèo]ogical characteristics. Therefore, the
test methods briefly described here represent our understanding of those
which in the opinion of qualified experts appe5r to'produce the most
reliable data under the present state of the art. The number of animals,
duration of the tests, costs~ ~tc. are often presented as a range to
reflect the various methods currently employed in a variety of labcra-
tories. See Table IV.
A. ~reclinfc~i~
1. Acute oral toxicity"4 - Six groups of 10-20 male and
10-20 female rats or mice are given a single oral dose of the test mate-
rial at graduated dose levels (generally spaced at 0.1 log dose intervals).
This is most of teu admit~istered by intubation. The animals are observed
for gross signs of systemic toxicity, pharmacological effects and mor-
tality frequently on the day of dosing, and at' least once daily during
the observation -period o~ 2-4 weeks. Autopsies are performed `on animals
that succumb. and on preferably all or at least selected survivors. It
is recomaended that two species of `animals be used to reveal possible
* species differences in toxicity. The Lb50 value and slope o~ the dose
response curve are calculated by one of the approved~thetbbds - such ~s the
Cornfield4fat*tel modification of Karber's6 method.
PAGENO="0164"
TABLE IV
MINIMUM REQUIREMENTS FOR SAFETY TESTS REQUIRED BY EAGLETON BILL
EIFOARIATIOW 109011OR SUGGESTED USURER 09 4815*1.0 APPROXIMATE
_b7~EACLET~!_!!74~ TEST ~(57~ 00 TEST SUBJECTS 5000T108 COBOBENTS ESTIMATED 01ST/F
EXPOSURE I.cboll.d *ot.ri.1.
D.gr~ of ins.nti.n ~ ,,i11 ~ ~ ~ 9008b
D.gros of inh.lotion LonGs .Saholotign rot 6 72 hr. .sti.co. of th. qoaotity of the prod-
R.gr.t of PAont.O*.gO 0.0 `bLob Right be ob.qrb.d by 5*0.
obsorption POroR000onna 600
absorption 910 6 .~ 72 hr. Sadiol.b.i1.d nstorLol itt.rt
and abrod.d .60*.
4855*1. STUDIES * Mitoopothelogy staloatiESsrsooonsndsd
Short-ORES - Lost. Oral .0'.. 6 greops 10-20 5 6 10-20 9 (120-240) 2-4 oaks at 011 do.ags 1oo~1.. 01000-2000
- rot 6 g*otps 10-20 5 6 10-20 F (120-240) 2-4 o..k. In S*bolotion sEodis. a lisitod nosb.r 1000-2500
Schalotion rat 6 gr..pa 10-20 * & 10-20 F (120-240) 2-4 n..ka of ~nk.y~ n.y b. noro appropriate for 1000-2000
tORt satsrioi*.
- d.r..1 (intano 0550-1000
* ORdabOOdcd.kin) rabbit 4grc.ap.-4-6 (167 2onnks IO505*0O5r5.abooR.o.~.tost.
night.b. d..Srcbl..
- Subsotto - oral Jrot 6 group. 10-20 0 10-20 F (120-2405 1-3 nootb. 910,000-30,000
idos 4 gr~p* 2-4 0 2-4 F (16-32) 1-3 .000ltg MO St 00a 1 t.d !EOR SF
- iobal*ti*n Oat 6 groops 5-10 8 6 5-10 F (60-120) 1-3 natO'. 0 50 509 nay 0 *000 Oppropratsop 7~15 000
- d.o.d rabbit 3-4 groups 6-8 (24-32) 21-90 day. *° ARt *000rials. 5,000-10,500
FDA Adnisory Cosnittos (1971) s.oonn.rdsd
Long-t.o. - Chronic - oral Jsoasa 4 groups 50 8 50 P (4007 2 ynor. inoladitg rsprodottjot ttody. 0.0 tonbins 585,000-150,055
Irot 4 gro.sps 50 S 50 F (400) 2 years ohrotio tocitity cod ooroiong..ioioy tsnt-
- ioholnnion ~.oo.. 4 ~rotpa 50 8 6 50 F (400) 2 yoaro ing. Rooosn.od ooposorn fron tr000ptiot 05,000-150,000
irot 4 grcaps 305 6 50 P (400) 2 yoors to dRain.
d.*nal rabbit 3-4 groop. In inOslatino gtadios a united nossbnr 59,000-85,000
10-20 8 6.10-20 P (80-160) 2 ysor. of nonkcys nay ho noru spproprioto for
Rondosly brad "Lifotin." eon, toot n00501ols.
- Carcin.g.no.0. {.000s 4 group. 50 S 6 50 F (400) 2-2 1/2 yoor. 2 y..r dog stody tot eon iar.d 085,000-150,000
tio.ol 25 S 6 25 F/oro.p 2-2 1/2 years
- M.tog.ne.i,
* - doniaast
1.thal souos 3 cr0.9. 10 8 & 30 P/,r..h (7508) 3 south.
- host s.di.n.d .ou.o 4 groops 3-10 (12-80) 1-2 nottbo Solcassilo on Rho test orgonion
- ~oj~tios rot 20 gro.p. 3-5 (60-100) 48 houra-l oh 1,000-2,500
- Tarotogassuis {rs.t 4 srcup. 13-25 5 & 25-50 F (152-300) 6-9 esoks $25 000-33 009
rabbit 4 gra.po 5-10 5 & 10-15 P (60-109) 6-9 nooks-
I A - Skin rabbit 6-12 (6-12) 72 hr - 2 .h... 0300-600
- Ey. rabbit 6-12 (6-12) 1-3 eke, 300-6
- Othon *50005 . 300-600
.ssbs0n.s rabbit or 000-2000
dog 6'12 (612) 48-72 ho.
Photosonsitiaing rabbit 9-12 (9-12) 2-3no.ka - 309-500
SAFETY FACTOR . to Dr. too Prlod.ao (FDA)
- at o 000 cession (1973). Vio,r hold by
nose noports.
SUSAN EXPESIENCE
Cootsot Snoaioi,ity~ p~50~ t.sn. hu.an. 100 5 6 100 F
Photes..sltiotty
(200) ~6o..ka
010,000-25,000
PAGENO="0165"
159
2. Acute in1ialationto~ç~ç4t4 - Six groups of 10-20 male and
10-20 female rats are placed in inhalation chambers and exposed under
controlled conditions for one hour to graduated atmospheric concentrations
of the test material in gaseous or aerosol form. The rats are observed
during the exposure period and daily for 2-4 weeks for gross signs of
systemic toxicity. Autopsies are performed on animals which die and on
all or selected survivors. -
A limited number of monkeys may be more appropriate for some
test materials.
3. Acute dermal toxicity~'4 - -Four groups of 4-6 rabbits
are prepared by clipping the hair from the trunk. Half of the animals
are further prepared by making epidermal abrasions e~tery two or three
centimeters longitudinally and sufficiently deep to penetrate the
stratum corneum but not deep enough to produce bleeding. A rubber or
plastic slee~je i~ placed on each animal and the test material is iptro-
duced under the sleeve at graduated dose levels. After 24 hours çhe
sleeves are removed, the volume of unabsorbed material is measured, the
skin reactions are noted and the animal is cleaned and placed in metab-
olism cages for a two-week observation period. The animals are checked
for gross signs of toxicity and blood and urine are examined for abnor-
malities. Autopsies are. performed on animals that die and on all or
selected survivors.
4. Subacute oral toxic1t~ - It *is recommended that at least
two species of animals be employed in this test to indicate if there are
species differences in toxicity. Six groups of 10-20 male and 10-20
female rats and four groups of 2-4 male aed 2-4 female dogs are given
daily oral doses of the material at graduated dose levels for 1-3 months.
The animals are observed for general condition, food and water consumption
and gross signs of toxicity. At regular intervals blood chemistry,
hematglogy and urinalysis tests are carried out. All animals are
autopsied at death orat sacrifice at the completion of the study and
examined for orgam weights and gross and microscopic pathology.
PAGENO="0166"
160
5. Subacute inhalation toxic~.t~ - Six groups of 5-10 male
and 5-10 female rats are exposed daily for 1-7 hours to graduated
atmospheric concentrations of the test material vapor or mist, or for
two continuous spray exposures (preferrably several hours apart) to an
aerosol preparation for graduated periods of time (e.g. 30 seconds).
Observations are made on syaptomatology, food and water intake, body
weight and of the blood for morphological changes. At the conclusion
of the study all animals are sacrificed and autopsied. }Iistopathological
examination is carried out on all major organs. Additional data on the
lung and chest effects may be obtained by comparing radiographs taken
prior to and immediately following a series of ex~wsures.
A limited number of monkeys may be more appropriate for some
test materials.
6. Subacute dermal toxicit~~ - Four groups of 6-8 rabbits
are dosed daily ior 90 days by application to clipped intact and/or
abraded skin at graduated dose levels. In some cases it may be a4equate
to use three groups of six rabbits dosed daily for 21 days on clipped
intact and abraded skin. In both cases the animals are observed
throughout the study for symptomatology, food and water consumption and
body weight. Blood and urine are examined periodically. All animals
are autopsied at the conclusion of the experiment. Histopathological
evaluations are generally restricted to the area of application and major
organs.
7. Chronic oral toxiciç~~ - At least four groups of about
50 male and 50 female rats or mice are administered daily oral doses of
the test material. This is most often introduced into the diet. If
carcinogenicity testing is to be combined in the same study, the number
o~ animals in each group should be at least 50 males and 50 females.
Several animals of each sex at each dose level may be sacrificed at
intervals, e.g. 6, 12 and 18 months, for examination, Throughout the
Study the animals are observed for gross signs of toxicity, food and
PAGENO="0167"
161
water consumption, body weight and the appearance of tumors. At regular
inter~vals blood and urine samples are examined. At the conclusion of
the study allanimals are sacrificed and autopsied. The principal organs
are wejghed and preserved for histopathologic~al examination. If dogs
are used in evaluating chronic toxicity carcinogenicity, the study
should be continued for about seven years. The FT~A Advisory Committee2
in 1971 recommended that chronic toxicity testing should involve exposure
from'conception until death, and that chronic studies should include
reproduction tests.
8. Chronic Inhalation toxic4~,y~ - may be desirable for products
whose use involves exposure primarily by jnhalatipn. The procedure is the
same as in the 90-day subacute study, except, that exposure should continue
for 2 years. The number of animals to be examined is similar to the
chronic aral study.
If monkeys are the- -appropriate species 4-8 ~ and 4-8 ?/dosage
level are udlized. , -
9. Chronic dermal toxic~y - may be necessary for preparations
which are usually applied to the skin daily for long periods of time. The
procedure is similar to the subacute dermal toxicity test but with greater
numbers of animals.
10. Carcinogenesis3!~ - As noted above "lifetime" carcinogenesis
studies in rodents may be combined with chronic toxicity testing to elitsi-
nate some duplication of effort. At the present time the only recommended
methods for carcinogenesis testing are "lifetime" (2-2 1/2 years) studies
in rodents or seven-year studies in dogs. More raptd screening methods
utilizing other species, microbiological techniques, etc. are being
investigated for reliability. One of the more promising of these involves
injecting the test material into a pregnant hamster and removing the
exposed embryos 48 to 72 hours later. The embryonic cells are grown in
tissue culture. Cancerous transformation is detected by standard
PAGENO="0168"
162
microscopic study of colony morphology. Neoplastic transformation is
confirmed by injecting the transformed cells into healthy x-irradiated
weanling hamsters to see if they produce tumors. Changes. in colony
morphology can often be seen within two weeks. In the trials to date
three to 16 weeks were required for tumors to develop in the healthy
animalS, although the animals were observed for one year. If this method
is confirmed as being reliable it would result in considerable savings
of both cost and time in earcinogenesis testing. -
11. Mutagenici~y~ - There is no one, recommended method for
deteeting mutagenic effects due to a chemical. Methods with a high degree
of presumptive human relevance include invivo cytogenetics, the host-
mediated assay, and the dominant lethal assay.
In the dominant lethal assay three groups of 10 males (mice
or rats) are treated by an appropriate route and are mated during sequen-
tial weekly periods with groups of untreated virgin females (3 per male)
for a total ~f 8 weeks. The females are sacrificed in mid-pregnancy (Day
12 or 13 for mice) and scored for total implants comprising early and
late fetal deaths and living fetuses.
In the host mediated assay an indicator organism (Salmonella)
is injected into the peritoneal cavity of a mammal. About four groups
of 3-10 host animals (mice or rats) are then treated with the test
compdtind by an appropriate route other than ~intraperitoneal. Several
hours later the hosts are killed and the indicator organism is recovered
and scored for mutants.
In the in vivo cytogenetics assay the test compound is
administered to four groups of 4 animals (mice or rats) by an appropriate
route. Bone marrow and/or lymphocyte samples are taken at intervals by
biopsy or at sacrifice of the animals and the chromosomes are examined.
12. Teratogenesis2 - It is recommended that studies of
PAGENO="0169"
163
teratogenesis be carried out in at least two species. The mouse, rat,
hamster and rabbit are suitable species. Four groups of at least 25
female rats or 15 female rabbits are treated with the test material by
an appropriate route for at least 14 days prior to mating and during
pregnancy. The day sperm are detected in a vaginal smear is considered
Day 0. All dams are observed daily for changes in appearance or behavior.
Autopsies are performed on all animals that die. Surviving animals are
sacrificed at Day 20 or 21 for mice and rats, respectively and Day .30
for. rabbits an~ the fetuses and reproductive organs are examined. The
number of dead and resorbed and living fetuses are recorded. The
fetuses are examined for external, visceral and skeletal malformations.
13. Skin irritation"4 - Primary irritation of the skin is
measured by a patch-test technique on the abraded and intact skin of a
minimum of six albino rabbits per preparation tested. Equal numbers of
exposures are made on abraded and intact skin. The abrasions should cut
through the stratum corneuin, but not into the derma. These animals often
are observed for 2 weeks to monitor lesions and their return to nQrtnal
condition. The test substance is introduced under a one-inch patch and
the animals is immobilized and wrapped if rubberized cloth or plastic
for 24 hours. The skin is examined at the end of the 24-hour period and
again at 72 hours.
14. Eye irritation1'4 - The test material is instilled into
one eye of 6-12 albino rabbits. The other ~ye serves as the control.
In one-third of the animals the treated eye is left unwashed. In the
remaining animals the eye is washed two seconds or four seconds follow-
ing treatment. The eye is examined at 24, 48 and 72 hours and at 4 and
7 days after treatment or as long as injury persists.
15. Irritation of other mucous, rnembranes~ - For some prepar-
ations it may be necessary to determine irritation to vaginal or penile
mucosa. For the former the dog is the species of choice - although the.
rabbit is the preferred species for other tests on mucous membranes.
PAGENO="0170"
164
The preparation is applied as directed and in excessive amounts to
6-12 animals. Reactions are read at 1, 2, 24, 48 and 72 hours after
application.
16. Skin sensitization1'4 - The hair on the back and flanks
of 6-12 male guinea pigs is removed by close clipping. The material
being tested is injected intracutaneously every other day or three times
weekly until.a total of ten injections have been given. The injections
are made at rahdom over the back and upper flanks. Two weeks after the
tenth injection a retest injection is made just below the region of the
previous injections. After 24 hours readings are made of the dIameter,
height and color of reaction ~re compared with the reactions after the
initial injections.
17. PhotosensitIzation1 - Nine-twelve albino rabbits are
exposed to UV irradiation to determine the amount which constitutes a
suberythemal dose. Six of the rabbits are then treated with the test
substance. All of the rabbits are exposed once daily until a total of
10 exposures (2' weeks) has been made. The degree of photosensitization
is determined by comparison of the local effects in the treated and
untreated subjects.
B. Clinical
1. Skin sensitization1 Human tests should employ at least
200 individuals (100 male and 100 female) covering a range of ages
appropriate for the product. The test material is applied by patch to
an area on the arms or back. The patch is removed after 24 hours and
a reading of the reaction is made. The area of erythema and edema is
measured. The subjects are given a day's rest and then given a second
patch application. This procedure is repeated until a series of ten
consecutive exposures has been completed. The subjects are then given
10 to 14 day's rest after which a challenge dose is applied once. A
comparison ~s made of reactions observed during the ten sensitizing
PAGENO="0171"
165
doses with the reaction following the challenge dose.
In some cases a "use" test where the product is distributed
to a large test panel for use according to directions is conducted.
However, the method lacks supervision and is generally considered leas
satisfactory.
2. Photosensitiza~i~çp, Photosensitizing potential of a
material is tested by determining the reaction to 1W irradiation follow-
ing treatment with the material. A large populatLon of appropriate
subjects is necessary for adeqtiate testingand the testshotjld only be
made if animal testing has failed to provide evidence of photosensitization.
PAGENO="0172"
166
SOURCES
1. Association of .Food and Drug Officials of the United States
* "Appraisal of Safety of Chemicals in Foods, Drugs and Cosmetics"
1959.
2. Food and Drug Administration Advisory Committee on Protocols for
Safety Evaluations: Panel on Reproduction Report on Reproduction
Studies i0 the Safety Evaluation of Food Additives and Pesticide
* Residues. Toxicol. Appl. Pharmacol. 16:264-296, 1970.
3. Food and Drug Administration Advisory Committee on Protocols for
Safety Evaluation: Panel on Carcinogenesis Report on Cancer Testing
in the Safety Evaluation, of Food Additives and Pesticides. Toxicol.
Appl. Pharmacol. 20:419-438, 1971.
4. M. J. Thomas and P. A. Majors. "Animal, Human and Microbiological
Testing of Cosmetic Products." J. Soc. Cosmet. Chem. 24:135-146,
1973.
5. Anon. Screening for Chemical Carcinogens. Lab Animal Sept.-Oct.:
39-40, 1973.'
6. CQrnfie1d~and Mantel. J.A.S.A. 45:193, 1950.
7. Health and Welfare, Canada. The Testing of Chemicals for
Carcinogenicity, Mutagenicity, Terat~ogenicity. September
1973.
PAGENO="0173"
167
VI A - DISCUSSION OF PERSONNEL REQUIREN~NTS
FOR PRODUCT SAFETY TESTING
In safety testing of foods, drugs and cosmetics the scientific
and professional staff most likely to be involved are toxicologists,
pharmacologists and pathologists. To estimate the present number of
scientists with these specialties, the 1972-1973 membership lists of the
Society of Toxicology, The American Society of Pharmacology and Experi-
in~ntal Therapeutics, The American Society for Experimental Pathology and
The American College of Veterinary Pathologists were examined. There is
some overlap in memberships of these societies so an attempt was made
to ensure that individuals with dual or multiple memberships would not
be counted more than once. From these membership rosters it was deter-
mined that the numbers of active U.S. members employed in academia, in-
dustry or government are 344 toxicologists, 1595 pharmacologists, 1078
experimental ,pathologists and 262 veterinary pathologists. Among these,
10 toxicologists, 155 pharmacologists and 247 pathologists are assdciated
with hospital and medical centers and may be engaged full time it~ clini-
cal actiyities. These figures may also g4ve some indication of the
relative numbers of personnel available to do clinical studies as compared
to prec~inica1 studies.
It is reasonable to assume that among these specialists needed
fox safety testing the most limiting would be the number of pathologists,
since pathologists would be required to interpret the microscope slides
produced in the course of testing. No other scientist could properly
perform this task. The need for an adequate number of qualified patholo-
gists was underlined only last month by the designation of the training
of experimental pathologists as a critical area among the National Cancer
Plan Project Areas. It was estimated above that there are 1078 experi-
mental pathologists and 262 veterinary pathologists active in the United
States. It was assumed that members of the American College of Patholo~-
gists would be either engaged full time in patient-oriented work and
PAGENO="0174"
168
hospital-related research, or, if interestedin outside research, would
be listed among the members of the American Society for Experimental
Pathology. Therefore, it was assumed that there are now about 1340
pathologists available in this country who could participate in safety
testing. It was further assumed that those pathologists who might be
interested in participating in the safety evaluation of cosmetics would
be able to spend not more than half of their time on this work because
of current cbmipitments in other areas. We recognized that the amount of
time required by the pathologist to evaluate each slide could vary
tremendously depending on the nature of the lesions involved. However,
if one assumes that the average number of slides that might be evaluated
per day by a pathologist is 200, each cont~a1ning one or more sections of
a given organ, the number of slides resulting from cosmetic safety
evaluations which each pathologist might be able to process would be 100
per day or 500 per week. Using these figures the total work load capa-
bilities of the pathologists presently available would be 670,000 slides
per week..
The proposed Eagleton Bill requires that each product ~nd each
ingredient of cosmetics, fragrances and tbiletries be tested for safety.
As noted in a previous section of this report, the total number of cur-
rently existing products and ingredients has not yet been determi'i~ed.
However, the number of products is now definitely known to exceed 24,000
and the number of ingredients appears to be in the order of 1500. The
testS required for each cosmetic product would, of course, vary with the
nature of the product and its proposed use. Since the number of each
type of cosmetic (face powder, lipstick, perfume, after-shave lotion,
deodorant, etc.) contributing to the total number of products is not
known at this time, for the purpose of estimating the work load involved,
we have assumed that one third of the products would require testing by
only one route of administration e.g. oral; one third would require test-
ing by two routes e.g. oral and dermal; and one third would require test-
in~ by three routes e,g. oral, dermal and inhalation. Concerning the
ingredients,it may be adequate to test by one route of administration only.
PAGENO="0175"
169
Using these estimates, 9500products and ingredie~nts would be tested by
one route, 8000 by two routes and 8000 by three routes.
For the relatively complete testing by each route of administra-
tion as outlined in Table IV a minimum number of animals (mice, rats,
rai~bits, dogs etc.), used in acute, subacute, chronic, carcinogenesis
and irritation of mucous membrane studies on which micropathology would
be required would be 1576 for test materials administered by the oral
route only, 1712 for materials tested by oral and dermal routes and
3102 for materials tested orally, dermally and by inhalation. The number
of slides for each animal varies depending on the species and on the test
performed but might conservatively average, about 20 slides per animal.
Therefore, there would be 31,520 slides produced for each product tested
by one route, 34,240 for each product tested by two routes and 62,040
for each product tested by three routes. These figures do not include
the slides produced in testing for mutagenicity since these slides often
are evaluated by inicrobiologists and cytogeneticists and might not neces-
sitate a pathologist. Using the number of products and ingredients esti-
mated above, tile total number of slides produced would be 299,440:000
for materials tested by one route, 273,920,000 for materials tested by
two routes and 496, 320,000 for the materials tested by three routes.
The number of slides produced in testing all of the cosmetic products
and ingredients currently on the market, therefbre, might be 1,069,680,000,
all of which must be interpreted by a qualified pathologist. Since the
estimated additional work load which the available pathologists might be
able to assume is 670,000 slides per wtek, it would take approximately
1597 weeks or about 30 years to evaluate the slides generated in this
program.
PAGENO="0176"
170
NUMBER OF NENUERS or THE SOCIETY OF TOXICOLOGY
Member' s Designation
of
Principal Activity No.
Academic (A) 179
Government(G) 103
Industry (I) 202
Consultant (C) 31
Retired (R) 13
Other (0) 13
*
Not indicated 74
AGorAGC 10
ACorACR 13
CRorCO 2
AIC, IC,. ICO, ICR, `AGIC, Al, 10, dO 18
- 658
Total number of members . . . . . 658
Foreign members 75
Retired or semi-retired 17
No. of active U. S. members 566
No. of members who are also members of one
or more of the Societies of Pharmacology
and Experimental Therapeutics and Experi-
mental Pathology or the American College
of Veterinary Pathologists 232
No. of Toxicologists not included in
other' societies 334
*(Apparently a similar distribution'of activities as those indicating).
PAGENO="0177"
171
ANERICAN SOCIETY FOR PHARMACOLOGY AN]) EXPERIMENTA THERAPEUTICS
Total Number of Members - 1856
Honorary Members - 3
Retired Men~bers L15
Foreign Members 95
Members also ~nembers of Society for Exptl. Pathology ______
Number of Active U. S. Members 1637
Members in Private Practice 42
Members in Academia, industry or government 1595
Of these active members 155 are associated with
hospitals and medical centers or drug abuse centers.
Many of these may be involved full time in clinical
practice.
AMERICAN SOCIETY FOR EXPERIMENTAL PATHOLOGY
Total Number of Members 12«=O
Honorary Members .17
Retired Members . 60
Foreign Members 64
Number of Active U. S. Members 1109
Members in Private Practice 33.
Members in Academia, industry or government 1078
Of these active members 247 are associated with
hospital and medical centers. Many of these may be
involved full time in clinical practice.
24-600 0 - 78 - 12
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172
AMERICAN COLLEGE OF VETERINARY PATHOLOGISTS
Total Number of Members 315
Foreign Members * 28
Number who are members of the Society for
Experimental Pathology 25
Members not included in other societies 262
SCIENTIFIC MANPOWER ENGAGED IN R&D ACTIVITIES
IN THE PHARMACEUTICAL INDUSTRY
An indication of the demand for scientists and technicians
(physicians, veterinarians, pathologists, toxicologists, pharmacologists,
biochemists, chemists, biologists, pharmacists, botanists, microbiologists,
nutritionists, etc.) for res~arch and development in the life sciences
can be gained from viewing as a grouj~ the scientific and professional
staff engaged ib R&D in the laboratories of the ethical pharmaceutical
industry. These laboratories are reportedly the second largest performers
of medical and health related research in the United States. Non-profit
institutions (colleges and universities, hospital and research institutes)
are the single largest performers and the laboratories and clinics of
the federal government rank third.
Public Health Service Publication No. 1443, Resources for
Medical Research, Report No. 8, March, 1966, entitled "Trends in R&D
Manpower in the Pharmaceutical Industry, 1959-65 and 1968" is used as the
principal information source. The data in the report are based on
information supplied, on a voluntary basis, by 100 member firms of the
Pharmaceutical Manufacturers Association with the consolidated data
PAGENO="0179"
173
analysis being performed by National Institutes of Health. The 100
companies included in the survey are estimated to represent more than
907. of the total ethical pharmaceutical industry sales and probably
about that same percentage of R&D manpower.
The R&D staff of pharmaceutical companies increased from 11,400
in 1959 to an estimated 16,400 in 1965 with a projected need of 19,000 by
the end of i96~8. For the entire period the R&D staff had increased at an
annual rate of 6%. The Pharmaceutical Manufacturers Association reports
that in 1972 the R&D staff of pharmaceutical companies increased to an
estimated 21,000. It is further estimated that more than three-fifths of
the medical and biological scientists employed by industry in R&D activi-
ties are on the staff of pharmaceutical companies. -
Table 5 summarizes the trends in en~p1oyment of R&D manpower in
the pharmaceutical industry, from 1959 to 1965 with estimates of R&D staff
in 1968 and ~972~.
TABLE 5.
R&D MANPOWER IN THE pHARNAq~EuncAL INDUSTRY
BY TYPE OF STAFF, i959-197Z~
Ty~e of Staff 1959 1960 1961 1964 1965 1968. l9t2
Scientific and Professional 6,632 7,155 7,336 8,047 8,890 10,430 11,040
Technicians and Supporting 4~780 5~16Q 6,128 7,008 7~QQ ~
Total R&D Mat~power 11,412 12,915 13,464 15,055 16,390 18,915 21,065
`Dept. HE&W PHS Publication 1443, Pharmaceutical Mt gs. Ass'n.,
Arthur D. Little, Inc.
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174
The estimated number of full-time employees engaged by the
pharmaceutical industry in R&D activities during 1972 according to level
of education are summarized in Table 61.
TABLE 6
Doctoral Less Than U.S.
Type of Staff Degree MD BS Bachelor's Total
Scientific and Professional 4,030 2,080 4,440 490 11,040
Technicians - 35 265 4,410 4,710
Supporting 250 255 485 4,325 5,315
U.S. Total ~4,280 2,-370 5,190 9,225 21,065
`Pharmaceutical Mfgs. Ass'n. estimates.
During the last 11 years (1961-1972) the pharmaceutical industry's
R&D staff has jncresed by approximately 8,000, and over the same time
period has maintained a high degree of stability in terms of the makeup of
its R&D staff. About 55% of the total R&D staff are scientists and
professionals, and 45% are technicians and supporting staff (Chart 1).
In 1961, of the total R&D staff by level of training approximately 25%
held doctoral degrees, 10% master's degrees, 25% bachelor's degrees and
4GZ less than bachelor's degrees. In the scientific and professional
staff category approximately 39% held doctoral degrees in 1964. In the
same category in 1972 approximately 37% held doctoral degrees.
Table 7 is a summary comparison for the years 1964 and 1972
of the estimated total scientific and professional staff engaged in
R&D in the pharmaceutical industry by level of training.'
TABLE 7
Scientific and Professional Staff
Level of Training 1964 Percent 1972 Percent
Doctoral 3,118 38.7 4,030 36.5
Less Than Doctoral ~ 61.3 7,010 63.5
Total 8,047 100.0 11,040 100.0
1Dept. }IE&W PHS Publication 1443, Pharmaceutical Mfgrs. Ass'n.,
Arthur D. Little, Inc.
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22,000
20,000
18,000
16,000
14,000
12,000
tiumber
of 10,000
R&D
8,000
Personnel
6,000
4,000
2,000
175
1961 1964 1965
16390
15055 - - -#
13464
3 54'
J~L ~i~ZZ~
21065
18915
/
Technicians
Supporting Staff
Scientific
&
Professional
: Staff
CHART 1
R&D Manpower In. the Pharmaceutical Industry by Type of Staff
1961 - 19721
1Dept. HEW PHS Publication 1443, Pharmaceutical Manufacturers Assoc.,
Arthur D. Little, Inc.
PAGENO="0182"
176
VI-B PRELIMINARY ESTIMATES OF FACILITIES AVAILABLE
FOR CONDUCTING PRODUCT SAFETY TESTING
The Animal Welfare Act of 1966 (Public Law 89-544) as ammended
by the Animal Welfare Act of 1970 (Public Law 91-579) (7 U.S.C. 2131
at seq.) requires the registration of all laboratory facilities including
those in acaçlemia, hospitals, industry, research institutes, etc., that
utilize animals for research purposes including product safety testing.
A current listing of the registered research facilities in the
United States appeared in the Federal Register, Vol. 37, No. 147, July
29, 1972. This listing, along with a more recent listing of additions
to the published list obtained from the U.S.D.A., shows a total of 775
registered research facilities in the United States including Puerto
4Uco.
A review of the listing was made to establish the types of
facilities in ~rder to further determine the potential number of.
laboratories that could be considered available to conduct the tests
described in Sec. V of this report and contained in the proposed legis-
lation (Eagleton Bill).
The table below summarizes the results of a review of the regis-
tered research facilities listing. .
Type of Facility Total Number
Universities and Hospitals 510
Industrial (Captive) 125
Independent 104
Government (Federal, State, County) 14
Other (Zoos, Museums, Associations, etc.) 22
Total 755
PAGENO="0183"
177
A review `of the 1972 American Council of Independent Labora-
tories, Directory of Toxicology Laboratories indicates a total of 23
independent toxicology laboratories. Across check ~f this directory
with the U.S.D.A. registered research facilities listing further indicates
that only 7 of the 23 are registered research facilities.
It is highly unlikely that even all of the 104 independent
registered research facilities out of the total of 775 listed would be
available to perform the preclinical (animal) studies required in the
proposed legislation.
PAGENO="0184"
178
VI-C OVERVIEW OF PERSONFEL AND FACILITIES
It is readily apparent from the information presented above
that additional bioscientific personnel and facilities will be required
to evaluate the more than 25,500 cosmetic products and their ingredients
as required by the proposed Eagleton Bill. A realistic indication of
how rapidly such a prograa might he initiated and expanded can be oh-
tamed by examining the growth record of the NCI Carcinogenesis Program.
Under this program the work is carried out by outside contractors in
addition to the NCI Frederick Cancer Research Center1 which was insti-
tuted about 2 1/2 years ago. . This large-scale bioassay program is
designed to determine the carcinogenicity and chronic toxicity in rats
and mice of chemicals including insecticides, herbicides, commercial
products and industrial compounds selected by the NCI. The test proto-
col states that fifty males and fifty females of each species are given
each compound at the maximum test dose (MTD) end 1/2 MTD. Twenty control
animals of edch sex are used for each compound. After necropsy 32 tissues
from each animal will be examined histologically.
We understand that in 1961-62 the initial Field Studies, as
they were designated at that time, were conducted by about 4 contractors
and were concerned with the effects of about 30 compounds. We also
understand that about 300 compounds will be under study during 1974.
Approximately 30 of these compounds will be investigated at the NCI
Frederick Cancer Research Center, the remainder by contractors. Using
this example two factors appear clear: 1) If one attempts to gather
appropriate personnel and facilities, building an entirely new organ-
ization such as the Frederick Center to conduct toxicity studies, more
than 2 years would be required for its assembly and the anticipated
initial capacity might be about 30 compounds/year; 2) Growth within the
NCI Carcinogenesis Program, in terms of the number of compounds/year
which have been studied from 1962-1973, has been in the order of 30
expanding to 300 or an increase of about 30 compounds/year. Comparing
these figures with ~ cosmetic products and their
ingredients to be evaluated shows the staggering nature of the task
outlined in the Eagleton Bill.
1Carcinogenesis Program - Second Annual Collaborative Conference,
November 25-29, 1973 El Tropicano Motel, San Antonio, Texas.
PAGENO="0185"
i79
Mr. RINALDO. Let us go now to the pretesting. Would an absolute
requirement, a statutory requirement, that all products be pretested,
have any such detrimental effect?
Mr. MERRITT. Here again, Congressman, the difference between
premark~t testing and premarket evaluation becomes very important.
When. you have a number of products-and I recognize the need to
be brief here-in which the changes are very minor and the experience
of those ingredients for possible chemical reaction is minimal, then a
premarket evaluation may show that the anticipated result would not
be one of detriment to the consumer. Testing, then, is not necessary.
If that evaluation results in a finding that testing should be done,
then it is up to the manufacturer to substantiate the safety of that
product by testing before he markets it.
Mr. RINALDO. I take it you contend that the manufacturer should
substantiate the safety of the product on a voluntary basis?
Mr. MERRITT. That is required by regulation by the Food and Drug
Adniinistration.
Mr. RINALDO. Is there really good reason not to require a mandatory
pretesting?
Mr. MERRITT. Pretesting?
Mr. RINALDO. Yes.
Mr. MERRITT. If you mandate a litany of tests, you could overload
the scientific community to such an extent that it could not handle
all the tests that would be required.
Mr. RINALDO. Let us go another step further down the line. It is
my understanding that you believe that the current system-safety
substantiation with FDA oversight-is sufficient to protect the
public.
Dr. Upton testified that. there exist something like 4~ million chem-
icals while testing capacity is only 200 to 500 tests a year. How can
we be so sure that the current safeguards are enough, based upon such
a small testing capacity?
In other words, is it not the fact that we really do not know? You
are telling me, and the committee, I assume, that you feel you have
enough information. You feel you can protect the industry and that
you can get by with this minimal amount of pre-test, but you really
are not sure are you?
I do not think you can say with any degree of certainty that you
are positive that you are performing enough tests, or that you are
really getting at the crux of the problem.
Is this correct?
Mr. MERRITT. I think basically the National Cancer Institute's
screening program is designed to attack the problem you are talking
about. They would pick those chemicals where the priority seems
highest and test those.
We believe that th~ priorities and the allocation of resources should
identify the areas where the injury is most likely to result and attack
those problems.
Mr. RINALDO. From their testimony, I gathered~ that they are
spending, in my opinion, an inadequate amount of money on tests
and that certainly it has to be bolstered and increased.
If my belief is correct, that the amount of i~oney spent on testing
has to be increased, do you feel that this is solely a function of the
PAGENO="0186"
180
NOT? Do you feel it is a governmental function? Do you think it is
an industry function? Or, do you feel it is some combination?
Certainly I think, we can all agree that more testing must be done.
Mr. MERRITT. Yes. I think it is a combination of responsibility. It
is a responsibility of the regulatory agency, the National Cancer
Institute, and the industry itself.
CTFA, as one step in this effort, developed and established the
cosmetic ingredient review program to conduct such a study on a
concentrated basis of all ingredients used in the industry. We `have
named an independent expert panel. We have permitted consumers
and the Food and Drug Administration to name representatives to
that panel and to meet with the panel to do, on a cooperative basis,
an open and independent review with a gathering of all the data of
all chemicals known to be used in the industry. They will develop
a priority for review of those chemicals and will solicit all industry,
governmental, and consumer input into this program.
That expert panel, then, independent as it is, and which meets the
Federal advisory committee requirements for independence, conducts
an ongoing review of these ingredients and does this on a cooperative
basis to keep the cost to the public-as well as to `the industry-to a
minimum. They make that data and the results of that review avail-
able to the entire industry, the scientific community, the regulatory
agencies, and the public.
Mr. RINALDO. Do you feel that would be adequate?
Mr. MERRITT. We feel it goes a long way in the present state of
the'art in being adequate.
Mr. RINALDO. But then you say in your statement, however, and
I will quote you: "Consumers should have the right to determine for
themselves the risks they are willing to take."
I am concerned. I wonder whether the consumer really knows what
type of risk he is subjecting his body to; that is, whether there is a
risk of cancer when he uses these products.
Therefore, I do not particularly understand the statement. I think
it is a highly significant one, but when you say that the consumers
should have the right to determine the risk for themselves, I think
we are really placing the burden on the wrong shoulders.
Mr. MERRITT. We are saying that the consumer should have the
right to make the judgment and to accept or reject the risk based on
the total body of science involved.
Mr. RINALDO. Mr. Chairman, may I follow up?
Mr. Moss. Yes.
Mr. RINALDO. If you say that, and if we accept that as true, then
why, do you oppose the FDA's labeling requirement? Specifically,
if T were to agree with you and say: "Well, let us let the consumer
make the judgment himself," then I would hope the consumer would
have the benefit of some kind of warning; perhaps some labeling
requirement to advise him of the potential risk. Otherwise, he is
making the determination in a complete vacuum.
Mr. MERRITT. Mr. Hutt commented on that. Perhaps he could
comment again.
Mr. HTJTT. Let me try to be very brief on that.
PAGENO="0187"
181
The industry at this point has nOt come to a final conclusion.
Therefore, we have some difficulty giving the definitive position of
CTFA on this.
However, the tentative position is that there is insufficient factual
information to justify singling out hair dyes for a specific warning.
The other part of this is this. There are many other hazards in
consumer products that every one of us subjects ourselves to every
day that are far more serious and bear no warning.
The OTFA does not believe that there is any justificatIon for singling
out one product that poses a relatively small risk and not pointing
out-
Mr. RINALDO. You are not answering the question as far as labeling
goes.
If you are opposed to the FDA labeling, then what kind of label
would you be in favor of?
Mr. HUTT. Mr. Gore suggested that consumers ought to be given
the information on the relative risks of all hazards. For example-
and I will just use one-the Food and Drug Administration has esti-
mated that its current guidelines for afiatoxin contamination of
peanuts will result in 66 bladder cancers per 100,000 lifetimes. That is
much higher than any risk that one can imagine or could possibly
calculate under any theory for hair dyes.
Yet, with that risk, there is no label warning for peanuts.
What CTFA says is:
If you are going to tell the public about risks from hair dyes, then you must
also tell the public about risks from caffine that is shown to be an animal carcino-
gen, egg yolks and egg whites that have been shown to be animal carcinogens, and
tannin in tea that has been shown to be an animal carcinogen-
Mr. Moss. The Chair has been indulgent. We have gone considerably
over the time allocated.
While it is an interesting narrative, `it is not really all important
in helping the committee make the decision that `it is going to make in
connection with these hearings.
I think it is demonstrated that you are all' capable of talking at
considerable length, but not necessarily constructively nor inst1~uctively.
The Chair recognizes the gentleman from New'Jersey, Mr. Maguire.
Mr. MAGUIRE. Thank you, Mr. Chairman.
Mr. Merritt, in the early 1970's, an ingredient in hair dyes, 2,4-
toluenediamine, was found to be a carcinogen. After this information
was made public, the hair dye industry removed it from its products.
Is that correct?
Mr.' MERRITT. I believe that~tO be correct. Dr. Corbett is much
more fully informed on those details than~I ani.
Mr. MAGUIRE. Let us aesume that* is correct unless somebody has
information to `the contrary.
Why was it removed?
Mr. MERRITT. I would again have to defer to Dr. Corbett on that
point.
Mr. MAGUIRE. You do not know the answer to that?
Mr. MERRITT. I do not. We want to provide informative answers.
Dr. Corbett is an expert and a scientist. I prefer that he answer that.
Mr. MAGUIRE. ~Dr. Corbett?
PAGENO="0188"
182
Dr. CORBETT. It was removed because there were reports that
under conditions of feeding animals 2,4-toluenediamine, that were
carried out in Japan, cancers were produced in the liver. The industry,
at that time, having no data of its own on that particular ingredient,
felt ~t wisest to drop its use.
Mr. MAGUIRE. A situation analogous to the one we have today with
respect to DAA?
Dr. CORBETT. Not at all.
Mr. MAGUIRE. The word "fatuous" is defined in the dictionary as
"delusive, self-deceiving, complacently or unconsciously stupid."
I have had time to reflect here as I have listened to this discussion
that perhaps that adjective is descriptive of what we are hearing
today from you gentlemen.
Did you replace TDA with another chemical?
Dr. CORBETT. Yes.
Mr. MAGUIRE. What was that?
Dr. CORBETT. It was m-phenylenediamine.
Mr. MAGUIRE. Is that similar to, or the same as, 2-4-diaminoani-
sole?
Dr. CORBETT. It is not the same material; no.
Mr~ MAGUIRE. Is it in the same family or class?
Dr. CORBETT. It is a m-diamine; yes.
Mr. MAGUIRE. Did you increase the use of 2-4 diaminoanisole
after you removed the 2,4-TDA from your product?
Dr. C0RBETT. No. I am afraid your adviser has a lot of misinforma-
tion.
Mr. MAQUIRE. I did not ask for your gratituous comment. I am
asking the questions. You may supply me with the answers.
But you are aware that the two compounds, TDA and DAA, have
almost identical chemicals; is that correct?
Dr. CORBETT. They are similar, but I would not say "almost
identjcal." There is a significant difference.
Mr. MAGUIRE. Are you also aware that many biochemists would,
by looking at 2-4---DAA believe that the chances are more than 50
percent, that because of its structural similarity to 2,4-TDA, react
almost the same, that is, that it would also be a mutagen and a
potential carcinogen?
Dr.. CORBETT. I do not think they would come to that conclusion
just be looking at the structure. As I said., it has a very significant
difference.
Mr. MAGUIRE. But you have had data from the Ames test, I
believe, since 1975, with respect to specific tests on these specific
chemicals, have you not?
Dr. CORBETT. Yes, in terms of the Ames test.
Mr. MAGiJIRE. According to testimony that we have from Dr.
Ames, those results have been duplicated by other tests; is that
correct?
Dr. CORBETT. I have repeated that test myself and have gotten the
same results; yes.
Mr. MAGUIRE. We have TDA removed and you indicate that the
test showed carcinogenic property with respect to animals. Here
today you are telling us that you have no intention, as I understand
PAGENO="0189"
183
it, of doing anything about DAA, despite tests which show mutagenic-
ity and carcinogenicity.
It seems to me that is an anomaly, to put the most gentle word
upon it.
Do you still believe that TDA should be excluded from your
products?
Dr. CORBETT. I think I have to answer the question at length. 1
have answered all the other questions briefly.
The situation today does not give rise to an anomalous or fatuous
comment on our part.
In 1970, we had no data on 2,4-TDA. We did not even bother to
gather data on 2,4,-TDA, but we removed it from our product
there and then.
Today we are in a situation where we can cite already five groups of
animals that have been exposed topically throughout their lifetime
to hair dye compositions containing 2,4-diaminoanisole without a
problem.
The other difference is this 2,4-diaminoanisole is used at a rate-
and I think you have an accurate figure but I will have to do it off
the top of my head because I do not have it with me-of about
15,000 pounds a year; 2,4-TDA was used at about 100 pounds a year.
I would not be prepared to fall back on the epidemiological evide nce
of a long term exposure of the whole female hair dye user population
to 100 pounds of a compound a year, but I am certainly prepared to
fall back on it in respect of such widespread uses as has occurred
with 2,4-diaminoanisole.
So, I think it is a perfectly logical position that we take and not an
anomalous one at all.
Mr. MAGuIRE. Are you familjar with the scientific notion that it
is impossible to define a safe threshold with respect to a carcinogen?
Dr. COEBETT. I am familiar with the notion; yes.
Mr. MAGUIRE. Is it one which you embrace or reject as a scientist?
Dr. COEEETT. I just look at both sides. I cannot come down on one
side or the other. I have read and accepted the development of
theories which show that you can produce a mathematical model to
show that the threshold theory could indeed be true.
One of the things that I think is a misunderstanding about-
Mr. MAGUIRE. The evidence seems to point to the truth of a linear
hypothesis. What about that?
Mr. OOREETT. I would not say that is true at all. Not all of the
evidence. In fact, the tests which you are citing in terms of an animal
test went from a very high level of thyroid tumors at one dose level
and at a dose level that was only one-half of that, it went to no thyroid
tumors in excess-
Mr. MAGUIRE. So you are undecided on that point?
Dr. CORBETT. It is* a position on which all scientists are undecided.
Mr. MAGUIRE. In that case, let us assume for a moment that you
are right about that, which, of course, you are not. Quite a number of
scientists are very much convinced that there is no threshold. Certainly
none that we can identify now. We have hact testimony to that effect~
In the event, though, that you are right, as a matter of public
policy-and that is what we on this side of the table are coneertLed
PAGENO="0190"
184
with-would you say that it makes sense to act to protect the public
when we have tests which show carcinogenicity?
I remind you that there are very few compounds that show those
properties. Or, in the case of doubt, and assuming again that you are
correct, do we simply continue to expose the public to those
substances?
Dr. CORBETT. I am sorry. I lost the thread of your question half-
way through.
Mr. MAGUIRE. Mr. Merritt, do you have an answer to the question?
Mr. MERRITT. I think you have to look at the benefit and balance
it with the risk involved.
Mr. MAGUIRE. How do you justify the difference between TDA
and DAA, Mr. Merritt? One has been taken out and the other has
been left in.
Mr. MERRITT. At the time TDA was removed, it was because there
was an alternative. But with respect to the other, there is no
alternative.
Mr. MAGUIRE. There is no alternative?
Mr.MERRITT. That is correct.
Mr~ MAGUIRE. Have you pursued, over the last 40 years, since you
received your exemption for hair dyes, a study of alternatives?
Mr.,. MERRITT. I am sure the industry has looked, at every possible
chemical for use in hair dyes.
Mr. Moss. Have you really? The gentleman's time has expired.
At this point the Chair recognizes Mr. Elliot Segal of the staff.
Mr. SEGAL. Mr. Merritt, to clarify a point made before with respect
to nitrosamines, are you testifying that end-products containing
nitrosamines are safe or not safe?
Mr: MERRITT. We do not know at ~this point.
We take the position that nitrosamines are contaminants.
Mr. SEGAL. Would you testify that a product containing mtro-
samines presents a risk to its users, whether it is a contaminant or an
ingredient?
Mr. MERRITT. Not having been involved in all of the discussions,
with your permission, I will defer that to Dr. Estrin, our scientific
vice president, who has been in those committee discussions and has
heard discussions and points of view that I have not heard.
Mr1 SEGAL. Dr. Estrin?
Dr.~. ESTRIN. It is true that there is no evidence that there is risk to
human beings through the presence of nitrosamines in products.
It is the association's position that these are contaminants that must
be removed or brought to the lowest level possible.
Mr. SEGAL. Are you testifying that it is a risk?
Dr.' ESTRIN. I am testifying that I do not know what risks there are
through the use of nitrosamines. But on the other hand, since they are
contaminants, we are trying desperately to remove them from our
products.
Nitrosamines, as you know, are present everywhere in the environ-
ment. They are made by our own digestive systems, through reactions
of nitrites and amines. They are present in food products. Dr~ Fine
will testify later that they are present-
Mr, Moss. Again, unless it is necessary for the purpose of the record,,
we know this. We have heard it many times. It does not do us any good
to have it repeated time and time again.
PAGENO="0191"
185
Please be brief.
Mr. SEGAL. Do you believe that nitrosamines are carcinogenic?
Dr. ESTRIN. Some nitrosamines have been shown to be carcinogenic
in animals. To my knowledge none have been shown to be carcinogenic
in human beings.
Mr. SEGAL. Then you would presume they are not safe, that is, that
they present a risk in any product, whether it is a contaminant or
whether it is in there as an essential ingredient, if it is used by human
beings, and has a potential risk?
Is that not true?
Dr. ESTRIN. The question is how much of a potential risk.
Mr. SEGAL. Is it infinitesimal to a gross risk or any risk at all?
Dr. ESTRIN. I would have no way of knowing. I have no way of
knowing, becauae there is no evidence that it is a human carcinogen.
Mr. SEGAL. And, yet, in your statement you say that you haveS
taken all the steps to immediately convene a group and immediately
remove these from all the products that are known.
What if you cannot remove them? Are you then prepared to say
that you are going to leave them in?
Dr. ESTRIN. When we find that we can reduce them to the lowest
possible level, or eliminate them, then we will have to deal with the
question of benefit-risk just like we will have to do with every other
consumer product that contains like materials.
Mr. SEGAL. Are they on the market now? Are there products
that contain nitrosamines now on the shelves of stores?
Dr. ESTRIN. I would guess that there are. Dr. Fine published in
March 1977, that there were 27 products that he examined. Excuse
me, 13 of these products contained-
Mr. Moss. We know that. We have the Fine study.
Mr. SEGAL. Let us go through them. Max Factor ultralucent
whipped cream makeup. Does that have, or does it not have, nitros-
amines in it now?
Dr. ESTRIN. I would not know. I would not know about a particular
product.
Mr. SEGAL. Do you dispute Dr. Fine's studies and findings?
Dr. ESTRIN. I am not personally qualified to tell you. But I can
tell y~ou that many of our manufacturers sent duplicative samples to
Dr. Fine and not in all cases were the results reproducible.
This is a sophisticated new technique. A lot more wOrk has to be
done on it. We have confidence that it is a good technique and we are
using that technique as part of our research program, which is to
screen comprehensively the ingredients used in cosmetic products
for nitrosamine content.
Mr. SEGAL. Are there any products that were named by Dr. Fine,
and confirmed by FDA, as showing nitrosamines that you have done
a test on, and that you have determined do not contain nitrosamines?
Dr. ESTRIN. I have personally not done tests.
Mr. SEGAL. Has anybody within the Cosmetic, Toiletry, and
Fragrance Association done any such tests?
Mr. MERRITT. We have not done tests on. finished products. Our
sole goal is looking at the ingredients and the possible causative
factors of nitrosamine contamination of ingredients rather than
finished products.
PAGENO="0192"
186
Mr. SEGAL. So you have no reason to believe that the 25 products
identified by Dr. Fine's study a containing nitrosamines do not
contain nitrosamines today.
Is that correct?
Mr. MERRITT. We do not have any reason to believe it is true or
untrue.
Dr. ESTRIN. Of those 25 products, 13 nitrosamines at higher than
traces leveli~. You said that 25 contained nitrosamines.
Mr. SEctAL. Let me revise the question and ask you if the 13 that
have more than trace levels, in those 13 that he found contained
nitrosamines, are you prepared to say that you know or do not know
whether they contain them?
Dr. E5TRIN. I do not know personally.
Mr. SEGAL. Nobody within CTFA is prepared to say that they have
either tested these or confirmed the absence or presence?
Dr. ESTRIN. I receive reports from a few companies that they had
sent samples to Dr. Fine of the same material and received noncon-
firmatory findings. Other companies did receive confirmatory findings.
I do not know the names of the particular products and the particular
companies off-hand.
Mr. SEGAL. Mr. Chairman, could we have those supplied for the
record; that is, the names of those companies?
Mr. Moss. The material you have just described will be supplied for
the record at this point.
Is there objection to holding the record open to receiving it? Hearing
none, such will be the order.
[The following material was received for the record:]
PAGENO="0193"
187
Avon Products, Inc. Avon Topaze 100 ngfg
9 West 57th St. Lot #33096
New York, N.Y.
Revlon Research Center Revlon Young Blush >40 ng/g
945 Zerega Ave. Lot #621
Bronx, N.Y.
Max Factor, Irt~. Max Factor Ultralucent 25,000* ngfg
1655 McCadden Place Whipped Creme Make-up 48,000 ng/g
Hollywood, CA 90028
Revlon Research Revlon Moon Drops 3,700 ngfg
945 Zerega Ave. Lot #551
Bronx, N.Y.
Helena Rubenstein, Inc. Helena Rtibenstein >1,200 nglg
300 Park Ave. Silk Fashion
New York, N.Y. Lot #F11
Max Factor, Inc. Ma~t Factor Ultralucent trace~
1655 NcCadden Place Waterproof Makeup
Hollywood, CA 90028 Lot #509
Johnson & Johnson Research Johnsons's Baby Lotion 100 nglg
H. Research Bldg. tracet
Rte. #1
No. Brunswick, N.J.
Westwood Pharmaceuticals, Inc. Ken Lotion trace~
468 Zewitt St. Lot IJK'l4
Buffalo, N.Y.
Noxell Corporatiba Noxzema Skin Cteam 8~ ngfg
11050 York Road Lot #2754
Baltimore, ND
tt
0~ren Laboratories Nutraderm Dry ND
P.O. Box 34630 Skin Lotiot~
Dallas, TX Lot #5M251
24.600 0 78 13
PAGENO="0194"
188
NAME AND COMPANY uuui RESULTS
Beirsclorf, Inc. Nivea Cream Lotion trace~
P.O. Box 529 Lot. 116241
Duke Place
S. Norwalk, CT
Gillette Company Gillette Deep Magic trace~
Prudeittial Tower Building Lot #2366
Boston, M&
Sea & Ski Corporation Sea & Skin Suntan trace~
Henley & James Labs. Lotion
P.O. Bc'x 8082 Lot #11314
Philadelphia, PA
Almay, Inc. Almay Deep Mist traces
562 5th Ave. . Extra Rich Lotion
New York, N.Y. . Lot #504
Scholl, Inc. Scholl Cocoa Butter .
213 West Shore Lotion Lot //504 trace
Chicago, IL Scholl Rough Skin
Remover >140 ng/g
Bain de Soleil Bain de Soleil 47 ngfg
Div. of Lanvin-Charles of the Suntan Creme
Ritz Lot #922
New York, N.Y.
Leeming-Pacquin Extra Strength >22 ngfg
Division of Pfizer, Inc. Desitin
235 E. 42nd St.
New York, N.Y.
Clairol, Inc. Clairol Herbal 260 ngfg
2 BI*nchley Road Essence
Stamford, CT
JohnBreck, Inc. Breck Shampoo traca~
697 Route #46 . Dry Hair
Clifton, N.J. Lot #4177
Rogers Wholesalers, Inc. PPP Baby Shampoo 100 ng/g
(Distributor of Product) Lot //F29H
122-20 Nerrick Blvd.
Jamaica, N.L
Gilman Brothers, Inc. PPP Baby Shampoo 100 ng/g
(Distributor of Product) Lot #F29H
20 Freeport St.
Dorchester, NA
PAGENO="0195"
NAME AND COMPANY
189
PRODUCT
The Nennen Company
Hanover Ave.
t~rristown, N.J.
Sterliog Winthrop Research Inst.
Rerinsselaier, N.Y.
Proctor and Gamble, Inc..
P.O~. Box 599
Cincinnati, OH
Wella Corpora1~ion
524 Grand Ave.
Englewood, N.J.
Clairol, Inc.
2 Blathley Road
Stamford, CT
Helene Curtfs, Inc.
Nennen Baby
Magic Shampoo
Lot #5JH
Diaperene Cradól
Lot #Sl350L
Head & Shbulders
Shampoo
Lot 1!~065686,
Wella Balsam
Lot #5r14
Clairol Creme .68 nglg
Formula Hair Color
*
Identity of NDE1A confirmed by high resolution mass spectrometry
Trace, Less than 10 ng/g
ND, Less than 1 ngfg
trace~
NDtt
>70 ~ng/g
tracet
Hel~iie Curtis . . >27 ngfg
Everynight Extra~-Body
Conditioner Lot #1094
PAGENO="0196"
190
Mr. SEGAL. Dr. Corbett, I would like to switch to a statement you
make concerning hair dyes on October 17, 1977:
There is now a substantial body of research sponsored by the hair coloring
industry, and by respected outside scientists, which confirms the safety of hair
dyes.
Who were the outside respected scientists?
Mr. CORBETT. I must say I think "supports" would have been a
better word to use, rather than "confirms."
Mr. Moss. Would you speak up?
Mr. CORBETT. I said that I now think that "supports" would have
been a better word than "confirms."
Mr. SEGAL. You would not today use the phrase you used on Octo-
ber 17 that confirms the safety? You would like to change it?
Mr. CORBETT. I think it might be interpreted to mean that I really
believe that one could prove absolute safety. Of course, I do not be-
lieve that.
Mr. SEGAL. Let us use your revised statement with "supports"
versus "confirms." Could you identify those scientists that you feel,
that is, that you identified in that study of that time or your statement
at that time, who support the safety of hair dyes?
Mr. CORBETT. Yes. This work was done virtually all in independent
laboratories.
Mr. SEGAL. I am asking for names of individuals.
Mr. CORBETT. But I have to look up some of them because I do not
know who was the responsible person for the studies that were done.
Mr. SEGAL. Would you include Dr. Hammond?
Mr. CORBETT. Yes.
Mr. SEGAL. How about Dr. Meigs?
Mr. CORBETT. Yes.
Mr. SEGAL. What about Dr. Kinlen?
Mr. CORBETT. Yes.
Mr. SEGAL. What about Dr. Morgan?
Mr. CORBETT. Yes.
Mr. SEGAL. Dr. Urbach?
Mr. CORBETT. Yes.
Mr. SEGAL. You would at least include those individuals?
Mr. CORBETT. This is what I said. If you want a comprehensive
list, then read the list of people who published the work. That is what
you have just done.
Mr. SEGAL. Mr. Chairman, I would like to have inserted in the
record at this point an abstract of a study done under the supervision
of Dr. Meigs of Yale.
Mr. Moss. Is there objection?
Hearing none, that will be the order.
[The abstract referred to follows:]
ABSTRACT-CANCER INCIDENCE AMONGST COSMETOLOGISTS
(By Judy Wairath, Yale University)
The purpose of this study was to determine whether cancer incidence rates
among cosmetologists differ from normal. The population under study included
all cosmetologists in Connecticut who began hairdressing school before December
31, 1965. School teachers in Connecticut were used as a comparison group and
were matched individually to the cosmetologists by year of birth and sex. Cancer
PAGENO="0197"
191
incidence rates for the Connecticut population, specific for age, sex, calendar year
and cancer site were also compared with the observed incidence rates of the cosine-
tologists. Cancer cases were ascertained through linkage of the files of the study
subjects and matched comparison subjects with the files of the Connecticut
Tumor Registry. There did not appear to be an excess risk of cancer amongst
the cosmetologists in any site, with the exception of acute leukemia. This pre-
liminary finding does, however, need additional investigation.
Mr. SEGAIJ. You have seen this before. This is the one that was
alluded to by Congressman Gore in earlier testimony where he read-
and I will read it again:
Cancer cases were ascertained through linkage of our files. . . There did not appear
to be an excess risk of cancer amongst the cosmetologists in any site, with the
exception of acute leukemia.
Is acute leukemia a form of cancer?
Dr. CORBI~TT. Yes.
Mr. SEGAL. Would you say that finding a significant excess of acute
leukemia does not conform with the statement made on page 8 of
your testimony that:
There is no direct link found by these two definitive studies showing a link
between hair dyes and cancer?
Dr. CORB1~YrP. I think I answered this question earlier by saying that
Dr. Meigs is asking himself the question as to whether the excess was
due to the apparent absence of any cases of acute leukemia among
the teacher group.
This is something he particularly wishes to study.
But there are other studies that have gone over the broad range of
different sites of cancer which come down on the side of there being
no difference and no excess.
Mr. SEGAL. We are talking about one of the individuals and one of
the studies which you defined as one of the two definitive studies. One of
the two definitive studies found an excess of acute leukemia and ended
up indicating that more wo~rk needed to be done on its confirmation.
Is that not right?
Dr. CORBETT. Dr. Meigs said this. There was a letter to me on this
subject: "Our concern about leukemia is based on the results of tables
7.5, 7.9, and 7.11, as well as section 9, pages 74-76.
"These raise the question of whether some aspect of the work--"
Mr. Moss. The Chair will have to interrupt until the item being
read is identified and the members are in possession of a copy of it.
This is a hearing, after all. It is for the purpose of informing the
Members of Congress.
Dr. CORBETT. I am sorry. I thought it was a letter he wrote to me.
In fact, it is a letter that he wrote to you.
Mr. Moss. I do not care what it is. I want to know what you are
reading from.
There is no process of intellectual osmosis going on here. I want to
know what we are discussing.
I have the letter now.
Dr. CORBETT. It is dated January 17, 1978.
Mr. Moss. Do the other members have the document?
[Document passed out to members.]
[The letter referred to follows:]
PAGENO="0198"
192
CONNECTICUT CANCER EPIDEMIOLOGY PROGRAM
PROGRAM COUNCIL Connecticut Cancer Epidetniology Unit
~n College Street
Connectkut State Dept. of Health New Haven, Connecticut o6~ao
Connecticut State Medical Society i :~L.i.L~~fj~ (uo~) 436-59n4
University of Connecticut
Yale University J. Wtsmtt Metes, M.D., Director
January 17, 1978
John S Moss
Chairman
Subnctmmittee on Oversight
and Investigations of the
Committee on Interstate and
Foreign Commerce
WASHINGTON D.C. 20515
9ear Mr. Moss:
Thank you for your inquiry of December 28, 1977 in which you quoted a*
statement of the Cosmetic, Toiletry and Fragrance Association (CTFA) and noted
that I had been identified as the scientist who had provided information about
our study of cancer risks in cosmetologists. Our Opinion that cosmetologists
?in Connecticut had not experienced an excess overall risk of cancer was based
o~a preliminary report. It is confirmed by the complete report, which is en-
closed for your use, in the form of the copyrighted dissertation prepared by
.ludy Walrath, Ph.D., entitled "Cancer Incidence Amongst Cosmetologi~ts." The
research was conducted by Dr. Walrath with consultation from Cohn White, M.B.,
B.S., Professor of Public Health (Biometry) and me, with support from the
National Cancer Institute, Grant # l-ROl-CA-2O89O-O[~.
This first study leaves several important questions unanswered and we are
necking support for a second study to increase the size of the cosmetologist
group by about 401, and try to ascertain complete follow-up for all cosmetol-
ogists. Nevertheless, I believe we can provide comments that can help you and
members of your Committee at this time. With respect to CTFA, we have had
considerable technical assistance from them, as well as a small grant ($2500)
in each of two years, to assist us with our work in this occupational health
problem. it is essential that our interpretations of results be presented as
~clearly and unequivocally as possible to all persons with interests in this
lubject. Accordingly, we are providing CTPA with copies of this correspondence.
At a time when questions about "conflict of interest" are asked frequently,
it is appropriate to explain our relationship with CTFA. One of their principal
members, Clairol, Inc., has a plant as well as headquarters in Connecticut. We
have received and will continue to solicit information from Clairol about their
manufacturing processes as well as chemicals and processes pertinent to the
PAGENO="0199"
193
3. W. Meigs to Mr. Moss, continued .
occupational and consumer uses of their products in particular and other materials
used by cosmetologists and the public. We have not solicited nor received pay-
aent for consultant services froa either CTFA or Clairol.
With respect to your first question, we assumed that licensure as a cos-
metologisl implied substantial, frequent contact with hair care and other
cosmetic preparations, in amounts greater on the average than would be experienced
by persons in other occupational groups. Many different chemicals and combinations
have been involved in these contacts over the years to Which our ~idy applies.
Our observations of cosmetologists at wor1t~onfiraed that they havi ~pportunity
for many different kinds of exposures.,
The evidence that cosmetologists in Connecticut have almost certainly, as
a group, had far greater exposure to hair care a~d other cosmetic preparations
than teachers, as a group, permitted us to design the study without including
interviews with either cosmetologists or teachers. We do not expect to interview,
persons in either group at this time. We were concerned with poseible health
risks of any or all substances used regularly by cosmetologists in their occu-
pation, and our study cannot distinguish hypothetical risks limited to hair dyes
or any other specific hair care or other preparation used by cosmetologists.
The question whether use of hair dyes, in particular, has been associated
with greater than expected incidence o~ bladder cancer will be addressed in
Con~ec~icut during the year 1978. Our Unit ~s cooperating in a national study
sponSored by the Congress, the Food and flrug Administration aqd the National
Cancer Institute, on environmental ~isk factors, particularly saccharin and other
non-nutritive sweeteners, among persons who develop bladder cancer during 1978.
Both cases and suitably selected control subjects will be interviewed and questions
about hair dyes are included in the interview schedule. Results should be avail-
able in early 1979.
Your second question opens up a etudy design issue. We selected teachers
as a matched comparison group for cosmetologists because we had access to their
licensure records and because they were generally comparable to cosmetologists
with regard to income. Our results show differences between the cancer experience
of the two groups that are reasonably attributable to so-called "class" or
cultural differences for which income alone would not be a good indicator,
You may have noted that the total group of teachers experienced significantly
more cancers of the breast and of the body of the uterus (uterine corpus) than
the total group of cosmetologists. This result is not consistent with some pre-
vious reports that beauticiafls have had a higher than expected risk for these two
cancers. Our result would, however, fit the hypothesis that among the cohorts
we studied, teachers, and especially the older teachers might have had socio-
cultural characteristics differing from cosmetologists. Such characteristics
as higher proportion of single persona, later ages at marriage and of first
pregnancies, have been shown to associate with higher than expected breast cancer
PAGENO="0200"
194
J. W, Meigs to Mr. Moss, continued .
rates and lower than expected cervical cancer rates. Dr. Wairath's results on
cervical cancer occurrence among cosmetologists compared with teachers are
consistent with this socio-cultural hypothesis. Uterine corpus cancer risk has
varied in relation to use of exogenous estrogens. We have no information about
uses of estrogens by either cosmetologists or teachers.
With respect to the latter part of your second question and your third
questio~T, 1 hav~ `already noted the probable socio-cultural differences between
teachers and cosmetologists in Connecticut that tend to limit our ability to draw
firm conclusions ab~ut occupational risk factors. This first study was designed
to learn whether large excess cancer risks had been experienced by cosmetologists.
No significant overall difference was found between the cancer experience of the
two groups.
Dr. Walrath dealt with the limitations of cosmetologist-teacher comparisons
by assessing the experience of cosmetologists for whom definite follow-up infor-
mation was available and comparing it with the experience for the total Connecticut
population of similar sex, age and time period. This latter information was
available from the Connecticut Tumor, Registry, which has been in operation since
1935. The problem of this second method of cancer risk assessment was that, for
the initial study, incomplete follow-up information for cosmetologists reduced
the total person-years of risk that could be used for the statistical calculations.
Nevertheless, the results from this work were generally in support of the cos-
metologist-teacher comparisons. The method made it possible to calculate the
expected number of cases of cancer for any desired grouping of cosmetologists and
then to compare the number of cases of that cancer observed in the `selected group
with the number expected for such a group if the members had had average Connecticut
experience.
Results of application of this method are presented in Dr. Walrath's report.
Tables 7.5, pp 98, 99; 7.9, pp 104, 105; and 7.11, pp 107, 108 provide summaries.
Table 7.5 shows that the total number of cancers observed among cosmetologists
was about 72% of the expected total (71-73% depending on the method of calculstion).
This figure is called the Standardized Incidence Ratio (SIR). Table 7.11 gives
results adjusted to take account of an assumed "~iealthy worker effect." The
assumption is made that persons who reach working age and are healthy enough to
take jobs are less likely to develop cancer than the general population of com-.
parable ages. ror Table 7.11, the SIR is adjusted upward to 100% so that the
risks of cancers relative to each other can be detected more readily.
Table 7.5 shows that there were fewer than expected cases o~ cancer of the
breast, uterine cervix, body of uterus and ovary than expected. Although you did
not ask about lung' cancer, the question of lung cancer risk among cosmetologists
has been raised. You may wish to note that the SIR for lung cancer was 78%
(Table 7.5), while the adjusted SIR (Table 7.11) was about 100%.
PAGENO="0201"
~95
.1. W. Meigs to Mr. Moss, continued .
Our concern about leukemia is based on the results of 1~ables 7.5, 7.9
and 7.11 as well as section 9, pp, 74-76. These raise the question whether some
aspect of work as a cosmetologist may contribute to the development of leukemia.
Table 7.9 does not suggest anincreased risk with increased exposure, but a
slight excess number of cases over the expected value was noted in 4 of 5 cx-
posure groups. We believe these results, when coupled with a ~1apanese report
(Ishimura, see ref. on p. 137) are sufficient to justify a second, more comp].~te
and intensive study of cosmetologists in Connecticut.
If work as a cosmetologist increases the risk of leukemia to persons in
that occupation, it is essential to interpret such a possibility with full
appreciation of the uncertainties about practical implications. Any one or a
combination of several materials or perhaps working conditions of cosmetologists
might be important. Information available at this time provides us with no
basis for an assessment of the carcinogenic risks of any particular chemical,
This issue relates to your 4th question. We believe out s~tudy ii~4i'catCs
that cosmetologists have not experienced excess risks of cancer in gen*al, since
their overall Standardized Incidence Ratio was about 72Z of expected and the so~
called "healthy worker effect" is often associated with SIR values above that
level. This does not imply that there are no specific cancer risks in this
occupation. There may be a small excess risk for leukemia and this question should
be investigated further.
Our study, like other epidemiological studies, cannot be used to prove
"safety". The results seem at this time to be consistent with the view that none
of the materials with which cosmetologists in Connecticut had contact after 1938
was a highly carcinogenic material. Such materials included, but were not
limited to hair dyes.
If you have further questions I should be pleased to try to answer them.
Sincetely yours,
J. Wister ~deigs, M.
Director
Clinical Professor, Epidemiology
JWM:lp
cc: Dr. John Corbett
PAGENO="0202"
196
Mr. MERRITT. Mr. Chairman, while that is being distributed, may
I make a comment with respect to epidemiological studies?
Mr. Moss. Is it responsive to any inquiry?
Mr. MERRITT. It is related to the subject.
Mr. Moss. Is it responsive, to the inquiry. on discussion now?
Mr. MERRITT. We will hold it until later. I was trying to save the
committee's time.
Mr. Moss. That will be fine.
Dr. Corbett, you may proceed.
Dr. CORBETT. This is not the letter I thought it was. In the letter he
wrote to me, he did not go as far as this, but his conclusion is that:
"The' results are sufficient to justify a second and more complete and
intensive study of cosmetologists in Connecticut."
As I pointed out, there were a number of studies also where no excess
of leukemia occurred.
Mr. SEGAL. Were they the two definitive studies you referred to on
page 8 of your `testimony?
Di~. CORI~ETT. Yes.
Mr. SEGAL. Which of the other two definitive studies are there?
You' identify here: "We are concerned NIOSH has chosen to rely on
two epidemiological studies." This is page 8 of your prepared state-
ment by CTFA.
"And ignore two definitive epidemioiogical studies." One is the
American Cancer Society and the other is the Yale funded one, which
we are now talking about.
You are talking about other tests beyond those?
Dr. CORBETT. No; we are talking about just these tests.
Mr. SEGAL. We are saying that one of the two tests was the one that
found an excess of acute leukemia; is that right?
Dr. CORBETT. Yes.
Mr. SEGAL. And suggests there be further followup work on that; is
that right?
Dr. CORBETT. Yes.
Mr. SEGAL. Does that confirm the safety of hair dyes?
Dr. CORBETT. It does not confirm the safety of hair dyes.
Mr. SEGAL. It does or does not?
Dr. CORBETT. In absolute terms, no, but in general terms with the
data that we have from other sources, yes. We have animal data-
Mr. SEGAL. We are talking about epidemiology. Let us stay with
that.
You have identified two definitive ones. We have talked about one
of them. You have, in effect, changed the testimony. Now you say
these studies confirm the safety and the definitive study shows no risk.
We have now identified leukemia and we have identified a need for
a followup study, and, therefore, a potential risk. Is that not correct?
Dr. CORBETT. A possibility; yes.
Mr. SEGAL. Let us now ask about the second epidemiological study,
that is, the other definitive one, which is Dr. Hammond's study.
For identification purposes I would like to ask that a presentation
of Dr. Hammond's, which was made in April 1977, which is in the
member's folders, be inserted into the record at this point.
Mr. Moss. Is there objection?
Hearing none, such is the order.
PAGENO="0203"
197
[The material referred to follows:]
AMERICAN
CANCER
SOCIETY
NEWS SERVICE
777 THIRD AVENUE
NEW YORK. N.Y. $007 /UI1$~iCan Cau~er Society's
I2t2~ 377.2E00 NINETEEIITR SCIENCE WRITEP.S' SEMINAR
- Sd~asota Hyatt House
Sarasota, Florida
April 1 6, 1977
TI
TI'
~es'~ntation: Tuesday morning, April 5
For Release: W~NESDAY AM's, April 6
-- EXCERPTED FROM:
~OME NECATIV~ FI~DING~P~~J SMALl POX~
TETANUS AND DIPRTHERL~-VACC~NE~; B!LUTICIA~S)~
AND EVALUATION OF RISKS
E. CUYLER HIIMOND, Sc.D. (64), Vice President for Epidemiology and Statistics,
Mterican Cancer Society. Dr. Hammond was born in Baltimore, Md., and received
his Doctor of Science degree (Sc.D.) from Johns Hopkins tTtiiversity. He joined
the American Cancer Society in 1946 after serving in the U.S. Army A~r Force as
Asst. Chief of the statistics div1s~on, office of the Air Surgeon. Prior to this
he served four years with the Division of Industrial Hygiene. Dr. Hammond also
is adjunct professor in community medicine, Mt. Sinai School of Medicine; a
member of the scientific advisory panel of Research to Prevent Blindness, Inc.;
assocIate editor of Environmantal Research; advisory editor of Ca-A Cancer .~ournal
for C1I~ici~~; and a member of the Board of Directors and past presIdent of the
New Yora Academy of Son,'eo
PAGENO="0204"
108
SOME NEGATIVE FIflDINGS
(POLTO, SNALL POX, TETANUS AND DIPHTRERIA~VACCINtS~ BEAUTICIANS)
~D EVALUATION OF RISKS
E. Cuyler Hanunond, Sc.D.
Z~,.ø~peMedPt~j*~vrk `~thi ~
o~heb1ico-c~rc±nocsrd~~carc inogens-in
~ ectremc~
tthe~oth~.
Some people are alarmed., to a far greater degree than is
~ They fear to eat anything
but natural food grown without nan-made fertilizers and insenti-
cides and with nothing added later. They think that air pollution
will cause then to die of cancar as will contact with manifold
products of industry. They do not ask `what is harmful? They
ask "what, if anything, is safe?"
Some workers are fearful of losing their jobs in these
tines of unemployment. For example, a friend of mine, who had
reason to suspect that a certain substance with which he works
is carcinogenic, recently said to us: `For God sake don't prove
that it causes cancer. If you do, it will be banned and I
wifl ldse my job. At my age, I will never be able to find any
other decent job." This is not an uncommon attitude.
PAGENO="0205"
199
H~inn~ond
`~pàge2
A growing number of people are becoming annoyed if not angry
about the whole affair.
"What are they going to prohibit next? Sex?"
Many of these people express the opinion that government and
scientists should stop their meddling and leave people alone.
They are also becoming highly skeptical of pronouncements made
by "authorities" including medical and scientific "authprities".
If this attitude becomes widespread, it will seriotisly endanger
our efforts to control cancer.
It is not our object to frighten people. It is not our
object to put people Out of work; and it is certainly not our
object to take all pleasure out of life. Our object is to reduce
the risk of cancer in so far as it is feasible to do so. reas3.bility
depends upon many elements, riot the least of which are public
attitudes.
In ny~opinioti~thbt'~w~y to develop realistic attitudes is
t~frankly adlait the limitations in~ our present knowledge and in
~ between what we knew and
wI~r-weoiily stispéct.' And when we speak of risk, express the
degree of risk in terms which are me~ningLul to the aver~ine ~
~ t.t) .l~
exciting and j~e~V wide ~ttCfltiOfl in both the i~flj~ ~OSS
arid pu±~iic r.ewe Lt~~c~.' Negative findings ~ ~.`h~eh seem to
L~
~, ~f
PAGENO="0206"
200
Hammond
page 3
sho* that a substance is harmless - tend to be dull and there-
fore usually receive little attention. Fo~th-i-sreason,-IwilL
s~tart b~ describing several negative findings. They areof in-
t~erest only in that they tend to counteract unwarranted fears~.
Beauticians
There has been speculation that some, and perhaps many,
of the various chemical agents used by or on women for beauti-
ficataon are carcinogenic. This has caused worry among many
women - especIally among those most heavily exposed: beauticians.
Epidemiologic evidence is now available on this matter.
Over 1,000,000 men and women in 25 states were enrolled
in a long term study by volunteer workers of the American Can-
cer Society. Upon enrol0.memt, each of them answered a lengthy
questionnaire. P~ndings~presentedbeloware based upon data
ay~ilable after 13 years of trabimg.
Of some 589,000 female subjects - all of whom were over
the age of 30 and most of whom w~!e over the age of 145 at the
start of the study - 5,125 said that they were beauticians.
By the matched group procedure, we matched the beauticians with
non-beauticians on age, race, education1 place of residence
(large metropolitan area vs rural or less populated area),
amount of cigarette smoking, past history of cancer, and past
history of heart disease.
Matches were found for 5,117 of the 5,125 beauticians.
In most instances, many non-beauticians were found as matches
for each of the 5,117 beauticians. This increased the statisrn-
tlcal stability of the findings.
PAGENO="0207"
201
Hammond
Page ~
During the course of the st~d7, 32]. of the beauticians died.
Adjustedfor the sIze of the tw~ gr~~ and standardized for age,
351 of the~beauticians dIed, ThIs smal- difference (in favor of
the beauticians) is not statIstical].]! sigrIficant. 113 of the
beauticIans dIed of cancer. Adjusted for size of the two groups,
115 of the ncri~-beauticians dIed of cancer. p~~"1s'virtual1y
no dIfference. There-was not a single site of cancer from which
significantly more beauticians than non_beauticians d~.ed.
The fIndings were essentIally the same during each of
twelve successive years of tracIng.
I~exposure~associate&with.the occupation of beaUticiam
has resulted in an increase in death rates from cancer of any
s~t~;~the increase Is too small to show up in a study of over
5,000 people over a period of 13 years.
It could be that soz~e "beauty aid" introduced in recent
years is highly carcinogenic but tins not been used suff~.cieflt1Y
long for the effects to become atparent, *Therefore~in spite
~of our fIndIngs, I belIeve that all recently introduced "beauty
aids" (and those proposed for introductidn) should be tested
for possible carcinogenic effects.
Polio Vaccine (SV 9~~)
Research carried cut by virologists between ].9514 and early
1961 revealed that some batches of polio vaccine produced up to
that time were contaminated, with living simian virus )4Q (SV LW).
(Later, leading virologlsts told me that they thought that most
if not all of the batches produced up to that time were at least
PAGENO="0208"
TABLE I
b) If Death Rates are Increased from Age 40 on by:
PROBABILiTY OF SURVIVING TO AGES 65 AND 75
AND LIFE EXFECTArIC! FOR U.S. WHITE MM.ES STANTING AT AGE 20
a) If Death Rates are Increased from Age 20 on by:
U.S.
White Males
1974
1%
2%
5%
7%
10%
15%
25%
70.73
70.49
70.24
69.52
69.03
68.32
67.14
64.85
44.13
43.77
43.41
42.35
41.66
40.64
39.00
35.91
Prob. Surviving from
Age 20 to Age 65 (%)
Prob. Surviving from
Age 20 to Age 75 (%)
Life Expectancy
at Age 20 (yrs.)
Prob. Surviving from
Age 20 to Age 65 (%)
Prob. Surviving from
Age 20 to Age 75 (%)
Life Expectancy
at Age 20 (yrs.)
U.S.
White Males
1974
70.73
44.13
50.95
50%
59.44
29.19
46.23
50%
60.60
29.76
46.93
1%
70.52
43.79
50.85
100%
49.93
19.26
42.93
100%
51.88
20.02
44.22
70.30
43.44
50.75
200%
35.16
8.31
38.36
200%
37.98
8.98
4 0.61
5%
69.65
42.43~
50.45
7% 10%
69.22 68.58
41.77 40.80
50.26 49.98
15%
67.53
39.22
49.54
25%
65.47
36.25
48.71
PAGENO="0209"
PA!3LR II
PERCENT OF DEATUS FROM ALL CAUSES
FOR SELECTED CAUSES OF DEA~1I
White_Males, U.S. 1974
(.~,lx~! of Death
20-~9 30-39
-s--
ACE GROUP
4(3-49 50-~9 60-69 70-79 80+
all. Cavises
100.000 100.000 100.000 100.000 100.000 100.000 100.000
.41 ~`jc.~:ar
11.11/0
10,727
1i.rg
0.122
1.997
6.819
9.319
9.214
6.107
2.240
C~i~nL~;ctUtTh
0.216
1.147
1.696
2.458
2.921
2.803
1.158
`3Lc~e~ch
0.037
fl*315
.0.750
0.079
0.976
0.974
0.765
Liver
0.048
0.137
0.243
0.338
(3.393
0.326
0.206
Pancrt~as
0.041
0.366
0.929
1.346
1.321
1.108
0.654
ProaL.tto
0.03.1
0.014
0.130.
0.570
1.511
2.660
2.744
0i.~dder
0.004
u.082
0.226
0.458
0.738
0.916
0.762
Eidney
0.059
0.247
. 0.598
0.70~J
0.614
0.127
0.215
Lcukeiuia
1.024
1.261
0.789
0.701
0./56
0.793
0.646
1~c1)eu:ic Ht~rt Disease
0.898 11.390 31.880 39.265 40.400 40.819 42.466
PAGENO="0210"
204
Mr. SEGAL. On Monday of this week, Dr. Corbett, we had testi-
mony presented into the record criticizing the two NIOSH reports
by Dr. Alvin Feinstein. He described, in his criticizing the NIOSH
report, the following gross flaws and fallacies. This was entered into
the record on Monday.
Point No. 1:
Although the suspected ediologic agent is hair dyes, no effort was made to dis-
tinguish whether the person's occupation was labeled as hairdressers and cosme-
tologists actually used or was exposed to hair dyes.
Did Dr. Hammond meet this criteria?
Dr. CORBETT. I do not know.
Mr. SEGAL. I must state, Mr. Chairman, that he was asked that
question yesterday. He indicated he did not.
Since the category includes electrologists, manicurists, beauty schoolteachers,
shampooers, requests for scientific evidence would have included an inquiry to
determine whether the patients were, in fact, exposed.
Do you know whether an inquiry was made to find out whether
these cosmetologists in Dr. Hammond's study were, in fact, inter-
viewed?
Dr. CORBETP. No.
Mr. SEGAL. You do not know, or you know they were not?
DR. CORBETT. I do not know that they were interviewed on every
question.
Mr. SEGAL. Dr. Hammond indicated to us that they were not.
The second important gross flaw and fallacy described by Dr.
Feinstein was:
A second important item of scientific evidence is the dose response curve.
Was the risk of cancer greater in people who had used hair dyes in larger amounts
and for longer periods of employment? The investigators made no effort to
obtain such evidence.
Have you, or do you know whether or not Dr. Hammond ever
obtained such evidence?
Dr. CORBETT. I think he followed them for 13 years. I do not know
that he asked them when they started in the profession of hair dressing.
I think he made the assumption that since they were between 30
and 40 years old at the start of the study, that they had already been
in the profession for a number of years.
Mr. SEGAL. In a telephone conversation with him yesterday, he
indicated that he did not make an effort to obtain such evidence.
Now, we find that the first two gross flaws and fallacies described
by Dr. Feinstein refer to the same gross flaws and fallacies in the study
that you declare as one of the two definitive studies on epidemiology.
Do you still feel that would hold, that is, that you would stand
behind Dr. Hammond's study as a definitive study on epidemiology?
Dr. CORBETT. I think it is superior to the one that Dr. Feinstein-
Mr. SEGAL. That is not the question. Do you feel that it is a defin-
itive study on the epidemiology of hair dyes?
Dr. CORBETP. As far as it goes, yes.
Mr. SEGAL. May I read to you the last paragraph of Dr. Hammond's
statement? It says:
These findings-
PAGENO="0211"
205
it is the last three paragraphs~
These findings were essentially the same during each of the 12 successive years
of tracing. If exposure associated with the occupation of the beauticians has
resulted in an increase in death rates from cancer or any other site, the increase
is too small to show up in a study of oyer 5,~OO people over a period of 13 years.
~Do you know whether ~scientists generally feel that the period of
time of 13 years is sufficient to determine cancer?
lDr. CORBETT. They do not. I think this is on~ of the misunderstand-
ings there has been about Dr. Hammond's study. There is an assump-
tion that they all became hairdressers on day 1 of that 13 years.
I am sure that assumption is not justified.
Mr. S1~GAL. Do you know how many of them had exposures of
greater than 20 years out of the 5,000?
Dr. CORBETT. It would seem likely, given the fact-
Mr. SEGAL. Do you know how many?
Dr. OORBEPT. No.
Mr SEGAL The last paragraph says "It could be that some beauty
aid . . ."-and I am not sure what he means by "beauty aid"-but
would you know what he means by that, Dr. Corbett?
[No response.]
Mr. SEGAL.
introduced in recent years as highly carcinogenic, but has not been used
sufficiently for the effects to become apparent. Therefore, in spite of our findings,
I believe that our recently introduced beauty aids and those proposed for intro-
duction should be tested for possible carcinogenic effects~
Would you think that confirms safety of hair dyes?
Dr. COR~ETT. The hair dyes-as I have told you before this
morning-have been in use for 70 years. They are not recently
introduced.
Mr. SEGAL. Have they all been the same formulation?
Dr. CORBETT. As a chemist in this industry, I hide my head in
shame and say so: "Yes. We have very few new materials introduced
into hair dyes."
Mr. SEGAL. What about the general statement: "Some beauty aid
introduced in ~recent years could be highly carcinogenic."? Have
you introduced any new ingredients in hair dyes in the last 70 years?
Mr. OORBETT. Oh, yes. In the last 70 years, yes.
Mr. SEGAL. Do you think it is possible that a hair dye would fall
within this categorization of a "beauty aid"?
Mr. CORBEPT. Yes; I would think so.
Mr. SEGAL. So, based on the conclusion that he makes here, it is
possible that hair dyes are. within the purview of his study? They
might be classified as possibly introduced in the last several years as
being highly carcinogenic?
Would that be the case?
Dr. OORBETT. It could, yes. Whether it is likely, or not, is a subject
for considerable debate.
Mr. SEGAL. You mentioned before when we were talking about
the epidemiology-and I apologize for having cut you off at that point
because I intend to get to it now-but there was the issue of absorption.
PAGENO="0212"
206
We are talking about animal studies. There have been studies done
by the National Cancer Institute that have identified six agents
causing cancer in animals. Is that not true?
Dr. OORBETT. I believe so; yes.
Mr. SEGAL. For identification purposes, if you have the same chart
that we had on Monday, these include: 4-amino~2~nitrophenol;
2,4-diarninoanisole sulfate; direct black 38; direct blue 6; 2-nitro-
1 ,4-phenylenediamine; and 2,4-toluenediamine.
Is that correct?
Dr. CORBETT. That is correct.
Mr. SEGAL. An answer that you gave earlier this morning was
that-and at that point you were only talking about 2,4-DAA-but
you said it was found to cause cancer at high doses and therefore
presented a potential risk.
Is that correct?
Dr. CORBETT. In the absence of other data, yes.
Mr. SEGAL. In the absence of other data, you were prepared to say
that 2,4.DAA presents a potential risk based on animal studies; is
that correct?
Dr. CORBETT. Yes,
Mr. SEGAL. Would you make that same claim for the other five?
Yo~ have already said that in different ways on direct black 38 and
direct blue 6, that they were benzidine-derivatives that converted to
benzidine in the body; is that correct?
Dr. CORBETT. That is correct.
Mr. SEGAL. Would you make the same statement for the remaining
three?
Dr. CORBETT. The remaining three are the ones on which we have
animal test data of our own.
Mr. SEGAL. Were these feeding studies or skin paintings?
Dr. CORBETT. Skin painting studies.
Mr. SEGAL. Do you have data on feeding studies?
Dr. CORBETT. No.
Mr. SEGAL. You have no feeding data at all on any of the other
three?
Dr. CORBETT. Not for carcinogenicity.
Mr. SEGAL. All right. The next question, then, is this. Relative to
absorption, do you believe that these ingredients that are placed on
the scalp are absorbed into the human body?
Dr. CORBETT. It was precisely the recognition of this that got us
to institute our safety testing program back in the late 1960's.
Mr. SEGAL. And absorption goes into the bloodstream of human
beings?
Dr. C0RBETT. Yes.
Mr. SEGAL. And presumably is excreted or retained in the human
body; is that right? One or the other or a combination?
Dr. CORBETT. Or change or decomposed, et cetera.
Mr. SEGAL. Do you know for sure that all of the absorbed material
is excreted?
Dr. CORBETT. No; we do not.
Mr. SEGAL. Do you know for sure that a portion of it is retained in
the human body?
Dr. CORBETT. No; we do not know that either.
Mr. SEGAL. You have studies, however, that indicate that 80 to 90
percent is excreted within 3 or 4 or 5 days; is that right?
Dr. CoRB~TT. Yes.
PAGENO="0213"
207
Mr. S~GAL. Would that lead you to subtract from 100 percent and
say that in some cases, after 5 days, a portion of that material ab-
sorbed might remain in the human body?
Dr. CORBETT. If you qualify it by the word "might," then I could
agree with it. One of the problems with that type of experimentation
is that there is never 100 percent recovery, even if you take the body,
mascerate it, and determine the amount in the body and the amount
that came out. It never comes to 100 percent. The methodology is
not that accurate.
Mr. SEGAL. Do you know what happens to the amount that is
retained in the human body?
Dr. COEBETT. We do not even know it is.
Mr. SEGAL. Have you done studies to determine that?
Dr. CORBETT. If we would have done that, we would have known
that some is retained. We do not know it.
Mr. SEGAL. Does that lead you to then come out with the con-
clusion that you cannot tell with assurety that hair dyes are safe?
You cannot confirm and you cannot even support that hair dyes
are s.afe because you do not know what happens to the material
when it goes into the human body.
Is that right?
Dr. CORBETT. I think one does not have to know everything in
order to support a particular proposition. So, I think I can say
"supports."
Mr. SEGAL. You would not say "confirms" or "proves"?
Dr. CORBETT. I find it difficult, as a scientist, to keep being asked:
"Will I say that hair dyes are safe in the absolute sense?" when
everybody knows I cannot say that. As a scientist, I cannot.
Mr. SEGAL. But it is difficult for the American people to understa~id
that when on October 17, 1977, you said: "There is now a substantial
body of research, sponsored by the hair coloring industry, and by
respected outside scientists, which confirms the safety of hair dyes."
You are now saying that you do not believe that it confirms the
safety of hair dyes.
Dr. CORBETT. Each piece of evidence on its own confirms. It
does not mean confirms in the absolute sense. I can get into a rhe-
torical argument, but I am sure we do not want to. We are talking
about one word.
Mr. SEGAL. But we are also talking about how one describes to the
American public the safety and nonsafety of hair dyes.
Dr. CORBETT. If you really believe that the word "supports" would
mean something really different to the American public than the word
"confirms," then I apologize. I do not think it would be recognized
as a particularly different word, which is the reason that it was in
there in the first place.
Mr. SEGAL. We have gone down the list.
Mr. Moss. Let me get that again. I am a little puzzled. You care-
fully used the term "support" as a substitute for "confirms"?
Dr. CORBETT. Yes.
Mr. Moss. Now you say that you doubt if the American public
discerns any significant difference?
Dr. CORBETT. I do not think it is inconsistent.
PAGENO="0214"
208
Mr. Moss. I have been representing the American public for 30
years in public life. I have high regard for its intelligence. I think it
knows the difference between "support" and "confirm." It is partic-
ularly trUe when you relate the results of a scientific test or experiment
or study. There is a great difference. It is not a simple matter of
insignificant semantics. It is a matter of very substantive intent on
your own. part.
You want to change the word from "confirm" because it does not
"confirm" to "support" which might tend that at some point in the
future to "confirm." But in only "supports" at the moment?
Dr. CORBETT. Yes.
Mr. Moss. There is a great difference.
Dr. CORBETP. I said so at the beginning of the session.
Mr. Moss. You have not weighted the significance of your own
careful choice of words, or you do not demonstrate very much respect
for the intelligence of this large body of consumers.
Dr. CORBETP. I assure you it is the former.
Mr. Moss. I am glad to hear that it is the former.
Mr. SEGAL. Just to continue without going through each individual
scientific study that you indicated in the past that was used to
confirm..-and now you are saying "support," we asked each one of
the sciei~tists that was on the list that I mentioned before: Dr. Kinlen,
Dr. Morgan, Dr. Hammond, and Dr. Urbach, whether they felt
their materials supported it.
We used the word "confirm" of the safety of hair dyes. Without
exception, all of them said that would not be confirmed.
Many of them in response indicated that they could not support-
and I will use the word "support"-a positive conclusion from a
negative finding.
Do you believe that you can support a positive conclusion from a
negative finding?
Dr. CORBETT. That sounds a little tautological to me.
Mr. SEGAL. There is a significant difference, Dr. Corbett, if on one
hand you say, as Dr. Kinlen said-and I guess I will have to ask-
Dr. CORBETT. It is exactly the same question you asked before:
"Can I prove absolute safety?" I have already answered no. You
have asked the question in a different way this time.
Mr. ~EGAL. I am willing to understand that you no longer say you
can confirm, but I am willing to ask this.
Do you believe that these scientists will support your position?
Dr. COEBETT. I cannot understand why they would not say that
it "supports" the position.
Mr. ~EGAL. I would like to read the letter from Dr. Morgan sent
to Chairman Moss. I ask that it be inserted into the record.
Mr. Moss. Without objection, so ordered.
[The letter referred to follows :1
PAGENO="0215"
209
FACULTY OF MEDICINE `~
DEPARTMENT OF PREVENTIVE MEDIC1NE
AND BIOSTATISTICS
p~' / ~ UNIVEIISITY OF TORONTO
90 Gerrard StW Toronto Ontario
January 11, 1978
Mr. John E. Moss
HOuse of Representatives
Chairman
Subcommittee on Oversight
and Investigations
Congress of the United States
of America
Washington, D.C. 20515
Dear Mr. Moss:
Enclosed you will find a copy of the results of our study
conceroing the relationship of liairdyes to bladder cancer. I would
emphasize that this study was used by the industry without the consent
of any of the authors. Although ~e were unable to find any relation-
ship between hair dye use and bladder cancer, it is possible that such
a relationship may occur and be detectable with larger numbers of
patients. This does not mean that I believe our study "confirms the
safety of hair dyes." Rather, we have failed to demonstrate any asso-
ciation between hair dye use and bladder cancer.
Although I am cautious abqut interpreting our own results,
I would, hope that your committee would be equally cautious in the
evaluation of non-human data to assess eafety of compounds for humans.
Tours sincerely,
RWM/smk Robert W. ~oxg~n, M.D.
-Professor
End.
PAGENO="0216"
210
troduce new ideas and bring about de- 3. The medical development team
velopment without suppressing local mi- should provide for a flexible, planned
tiative. Accordingly, after 4 years the phase-out period in order to afford
team was withdrawn slowly, the last predictability and avoid suppressing
* MEDICO .phyaician leaving in 1968. local initiative.
Since that time the hospital has been 4. An educational program must be
without any foreign staff. This policy conducted on a continuous basis as it
was adhered to despite many requests is essential that permanent trainhd
for a longer period of service and such counterpart personnel be available.
* local comment towards the end of the 5. Outsiders should never compete
project as "this hospital will stop de- with the locally available service but
* . veloping as soon as you leave." add to it something that is new and
In November 1976 I returned to the unavailable.
Klsang District Hospital to see what 6. It in bad policy to supply dis-
* :.::~: had happened to our project and to posable equipment funded from abroad;
visit old friends. I found that progress only reusable equipment should be in-
had continued at a rapid rate and that troduced.
all the innovations we had introduced Unquestionably the great improve-
were functioning in an expanded form ment n economic conditions in Malay
The central sterile supply room h~ sia in the last decade has resulted in
~ operated at full capacity since we left improvement of medical services and
and now s ppli s two ope at g rooms has been the most important factor in
~ instead of one. The blood bank was the improvement of Malaysian mcdi-
functioning well An enlargement to the cine However the Kluang District
library and a lecture room had been Hospital would never have progressed
added. A completely new and larger without the help and leadership of the
laboratory had been built, was well CARE-MEDICO team. It was the
staffed and was capable of carrying out opinion of the physicians and other
an extensive range of complex bacterio- hospital staff that CARE-MEDICO
logic studies. Two roentgenogram ma- had concentrated the development into
chines were functioning and the inten- a short space of time, after which
::: sive care unit was busy and had been progress was easier.
moved closer to the operating room. Thanks go to the many individual
Full electronic monitoring and resusci- donors, volunteers and staff of CARE-
* . ~ tation were available. MEDICO and particularly to the many
The change was remarkable con interested Malaysians both in govern
sidering the situation in 1964 when ment and in the private sector, who
the hospital had only a small outpatient helped over the last decade to make
department with dispensary, several this Canadian project a success.
wards only one operating room and JOHN R TAYLOR MD FRcs(cl
a small laboratory where only a few 67O~ Finch Ave. W
tents could be performed. Toronto, Oct.
It was the opinion of the medical
staff that CARE-MEDICO had shown Hair dyes and bladder cancer
* .::~ the way with a pilot project of hospital
development that was later duplicated To the editor: Recent work has dem-
in many district hospitals in she region. onstráted the mutageniciey of hair dyes
::::~ It was encouraging that many young, in bacterial mutant systems.1' By far
recently graduated physicians at one the greatest number of dyes are known
time considered the addition of a labo- to be absorbed through the skin and,
ratory, an intensive care unit, a central therefore, on the assumption that most
sterile supply room and an improved carcinogens are also mutagens,3 dyes
..".:. operating room to be the norm in hos- must be regarded as potential car-
* ::::::; pital development. cinogens in man. It is speculated
The lessons we learned from thin un- that the carcinogenic or mutagenic ef-
dertaking can be summarized as fol- fects of these chemicals may be due
* .... lows: to their extensive reaction with deoxyri-
* 1. Development plans should be in- bonucleic acid.4-'
atituted in consultation with the local Although the results of earlier tents
government and only after considerable performed on dogs and rodents did not
time is spent working in the hospital indicate that hair dyes are carcino-
to reach conclusions as to what the gens" there is some preliminary epi-
hospital can beat use. demiologic evidence for this belief in
~. S~ve~ ~l h.spitvl departments should the higher incidence of bladder cancer
be developed to a certain equal level iii l.aiber~, hairdressers and beauti-
simultaneously rather than in sequence, cians.e~ However, a study from Massa-
on the principle that, for example, the chusetts discovered no excess risk
operating room, laboratory, blood bank, among female hairdressers.i Searle and
hospital wards and intensive care unit colleagues found some carcinogenic
are interdependent, activity in their tests on mice. Four
CMA JOURNAL/NOVEMBER 19, 1977/VOL. 117 lt3t
PAGENO="0217"
~w
z
o
m
2.
-
y
-3
3
PAGENO="0218"
212
Mr. SEGAL. It says:
Enclosed you will find a copy of the results of our study concerning the relation-
ship of hairdye~ to bladder cancer. I would emphasize that this study was used
by the industry without the consent of any of the authors.
Although we were unable to find any relationship between hair dye use and
bladder cancer, it is possible that such a relationship may occur and be detectable
with larger numbers of patients.
This does not mean that I believe our study "confirms the safety of hair dyes."
Rather, we have failed to demonstrate any association between hair dye use and
bladder cancer.
Do you think that letter can be used by you to say that Dr. Morgan
supports the safety of hair dyes?
Dr. CORBETP. I do not believe I ever used that letter. It was not
written to me.
Mr. SEGAIJ. No, but you used Dr. Morgan, from the Faculty of
Medicine, Department of Preventive Medicine and Biostatistics,
University of Toronto, Toronto, Canada, as one of the individuals
who, at that time, was used by you to confirm the safety of hair dyes.
I am now asking: "Do you think that this letter should be used by
you to indicate this supports the safety of hair dyes?"
Dr. COBBETT. Although I am cautious about interpreting our own
results, I would hope that your committee would, be equally cautious
in the evaluation of nonhuman data to assess the safety of compounds
for humans.
I do not see why not. His final sentence is again another way of
expressing the fact that one cannot prove absolute safety. So, you
get this equivocation all the time. It certainly supports the absence
of a relationship between bladder cancer and hair dyes.
Mr. SEGAL. He says: "We have failed to demonstrate any associa-
tion." Does that support safety?
Mr. COEBETT. It supports the position that is part and parcel of
the safety of hair dyes, namely, that there is no association between
hair dyes and the development of cancer.
That certainly supports the position. I cannot see where you are
going with this argument.
Mr. SEGAL. I have no further questions, Mr. Chairman.
Mr. Moss. The Chair wants to try now to come to a determination
for future scheduling. It is quite obvious that it will not be possible,
due to the nature of floor business now underway in the House Cham-
ber, to conclude these hearings today.
The Chair is of the opinion that we can dispense with the witnesses
now before us.
Does any member at this point have questions to direct to these
particular witnesses?
If not, the Chair will excuse them with the thanks of the committee.
We will announce very promptly, as soon as the Chair determines
the a~vai1abi1ity of members for tomorrow, whether or not we can
hear witnesses tomorrow or will have to defer for a week.
With that, the committee will stand adjourned at this time.
[Whereupon, at 12:40 p.m., the committee adjourned, subject to
the call of the Chair.]
PAGENO="0219"
CANCER-CAUSING CHEMICALS
Safety of Cosmetics and Hair Dyes
THUR8DA~,. PEBRUARY 2, 1978
HousE o~ REPRESENTATIVES,
SUBCOMMITr~E ON Ov~nsIGnT AND INVESTIGATIONS,
COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE,
Wa8hington, D.C.
The subcommittee met, pursuant to notice, at 10 a.m., in room
2322, Rayburn House Office Building, Hon. Andrew Maguire pre-
siding [Hon. John E. Moss, chairman].
Mr. MAGUIRE. The subcommittee will hem order.
Today we begin the third day of hearings on the "War .on Cancer."
We will cOntinue our focus on the safety of hair dyes and other cos-
metic products Earlier in this series, the subcommittee was informed
by the National Cancer Institute-NCI-that at least six hair dye
ingredients have been shown to be carcinogenic in animals. Two of
these ingredients are benzidine derivatives-a known human
carcinogen.
On the second day of hearings, we heard from representatives of
the Cosmetic, Toiletry and Fragrance Association-CTFA-that
they acknowledge the existence of nitrosamines, an extremely per-
vasive animal carcinogen, in numerous cosmetic products and were
committed to the elimination of these chemicals from their products.
Today, we will hear from Dr. David Fine who will present his scientific
results on nitrosamines in cosmetics.
With respect to the issue of hair dyes, CTFA representatives
acknowledged that ingredients of hair dyes were found to be muta~
genic by the Ames test and that hair dye ingredients found by the
Cancer Institute to be carcinogenic could be absorbed into the human
body and find their way into the human blood stream.
Testimony was also received demonstrating that industry' studies
are not available to determine whether these carcinogenic agents
are retained, or significantly metabolized into deleterious agents
inside the human body. Dr. John Corbett from CTFA testified that
as much as 10 percent of the amount of hair dye that is absorbed
into the human body might remain~there for a period of at least 3,
4, or 5 days.
There were several unanswered questions resulting from previous
testimony. We hope that testimony presented today will shed addi-
tional light upon these issues. These include, with respect to nitros-
amines, whether they are absorbed into the human. body and whether
the industry tests of ingredients as opposed to final products are
appropriate. In addition, with respect to hair dyes, the issue of
(213)
PAGENO="0220"
214
whether undertaking only skin painting studies is appropriate for
determination of safety will also be addressed.
I would first like to call upon Dr. Joseph Highland with the Environ-
mental Defense Fund.
TESTIMONY OP JOSEPH HIGHLAND, PH. D., DIRECTOR, TOXIC
CHEMICALS PROGRAM, ENVIRONMENTAL DEFENSE FUND, AND
LESLIE DACH, SCIENCE ASSOCIATE, ACCOMPANIED BY ANITA
JOHNSON, STAFF ATTORNEY, EDP; AND JOHN P. CORBETT, PH. D~,
CHAIRMAN, HAIR DYE TECHNICAL COMMITTEE, THE COSMETIC
TOILETRY AND FRAGRANCE ASSOCIATION
Dr. HIGHLAND. Thank you, Mr. Chairman. I would like to thank
you and the members of the committee for the opportunity to appear
here today. We will present a brief summary of the written statement
which we have given to the committee and hope that written state-
ment will be incorporated into the record.
Mr. MAGUIRE. Without objection your full statement will be
printed in the record [see p. 220].
Dr. HIGHLAND. I am Dr. Joseph Highland, director of the toxic
chemicais program of the Environmental Defense Fund. With me
today on my right is Leslie Dach, science associate at EDF. EDF is
a nonprofit public interest group with over 45,000 members. It has
long advocated the elimination of unnecessary human exposure to
toxic chemicals. In May and again in September of 1977 EDF testi-
fied before this committee on the regulation by the Consumer Products
Safety Commission on flame retardant Tris. In October 1977 EDF
petitiot~ed the Food and Drug Administration to require that all
hair dyes containing 4-methoxy-m-phenylenediamine carry a label
warning consumers of the cancer hazard posed by this chemical.
FDA proposed regulations accepting this petition in the Federal
Register January 6, 1977. In comments submitted to FDA on January
11, 1978, EDF has also asked that the provisional approval for the
use of the color additive lead acetate in hair dyes be terminated.
Lead acetate causes cancer in animals and has been shown to pene-
trate the skin of humans.
We are here today to discuss the health hazards posed by cosmetics.
Over $7 billion worth of cosmetics are sold each year. Currently
there are over 24,000 different cosmetic formulations containing about
8,000 ingredients. The American people are thus exposed to thousands
of cosmetic ingredients about which little if any health effects infor-
mation is available.
We ~an expect that many of these chemicals in cosmetics that we
put on our faces, hands, and heads enter our bodies. Some, like hair
dyes ingredients, absorb through the skin. Others, like lipsticks, are
ingested. In light of such vast human exposure and the potential for
harm, it can no longer be considered acceptable to allow the market-
ing of untested cosmetic ingredients. The legitimate concerns for
public health and well-being demand that action be taken immediately
to insure that every cosmetic product sold the American people is
safe for use.
PAGENO="0221"
215
You have heard a presentation by the Cosmetic, Toiletry &
Fragrance Association. What CTF4 has offered is a standard plea
for self-regulation. They agreed to the need for safety substantiation
prior to marketing but want to do it themselves by their own protocols
and without the involvement of the Food and Drug Administration.
This is simply unacceptable. They contend that cosmetics are safe
but they offer no scientific proof to establish this fact.
Even when faced with a situation in which N-nitrosodiethanola-
mine, a known carcinogen, is present in a variety of widely used
cosmetic products, the industry continues to question whether this
contaminant poses a potential hazard to public health and has failed
to take the necessary steps to resolve this critical issue.
Moreover, a careful review of the scientific evidence on what CTFA
claims is one of the best tested cosmetic products-hair dyes-clearly
reveals that their* pronouncements of safety are unsubstantiated by
fact.
CTFA asserts that Congress, by its own declarations, in 1938,
concluded that the benefits of cosmetics outweigh the risks caused
by their use. Obviously, the 1938 Food, Drug and Cosmetic Act was an.
attempt by Congress to insure public protection, not a declaration
accepting risk. But the events over the past decades indicate that
there is immedjate need today to revise the Food, Drug and Cosmetic
Act to better insure consumer protection.
CTFA claims that FDA already has substantial and sufficient
authority to regulate cosmetic products. Such a. statement borders
on being ludicrous in light of the fact that, in reality, FDA has no
statutory authority to require that manufacturers test their products
before they enter thefl marketplace. A cosmetic producer does not
violate the law even if it fails to conduct a single safety test either
before or after introducing a new product.
Moreover, the FDA has no authority to require cosmetic manu-
facturers to provide the necessary information that would enable the
agency to conduct its own premarket and evaluation.
Manufacturers cannot be compelled to submit ingredient lists,
consumer complaints, or test data to the agency.
Consumer products, such as hair dyes, sold for use in beauty salons
do not have to be labeled with th~ ingredients they contain. Cosmetic
manufacturers are not even required to inform the FDA that they
or their products exist.
Last week, in these hearings, OTFA claimed that further regulatory
authority was not needed by the FDA because the agency already
has promulgated regulations requiring any manufacturer who fails to
substantiate the safety of cosmetic~ products to include~ the following
statement on the product label. I' quote, "Warning, the safety of this
product has not been determined." .
This regulation has never been enforced by the FDA. The agency
authority to issue it has been questioned. Even if it were enforced, it
would be inadequate for the following reasons.
The FDA has no authority to inspect or require the submission of
data on which the manufacturer's safety claim is based. No definition
of safety is provided and the tests on which, the safety is to be deter-
mined are not described.
PAGENO="0222"
216
Moreover, the ~v~arning label as worded does not identify it for the
consumer whether an actual risk exists, and if it does, what the nature
of that risk is. Consumers could conceivably face shelves of cosmetics
full of such labeled products and be unable to make a judgment as to
which ~f the products to avoid~
Finally, CTFA contends that its own safety programs are sufficient
to insure the protection of public health. But the history of hair dyes
is a striking example of the contrary.
Mr. Dach and I would like to briefly review that history before
offering our closing remarks.
Almost 33 million Americans regularly dye their hair. This figure
represents nearly 40 percent over the age of 15 and almost 50 percent
of all women over the age of 40. Consumers spend over $300 million a
year on hair dyes. The vast majority of hair dyes are known as. coal
tar dyes because the dye chemicals used to be derived from coal tar
from the distillation of bituminous coal.
It is these dyes that we will focus our remarks on. It is these dyes
that the industry contends have been shown to be safe for use.
Our written testimony reviews in detail the scientific evidence
compiled to date upon which a judgment of safety or risk must be
made. We believe without a doubt that this evidence fails to establish
the safety of hair dyes. Rather, it supports our contention that very
real risks exist to consumers using these products.
Mr. Dach will now summarize the data on five important parameters
relating to hair dye risk: absorption, teratogenicity, mutagenicity,
carciziogenicity, and epidemiology.
TESTIMONY OF LESLIE DACH
Mr. DAd. Everything we know about hair dye ingredients indi-
cates that they penetrate the skin. All hair dye ingredients so far
tested, whether semipermanent or permanent, including chemicals
similar to the structure of the benzidine-derived dyes discussed last
week that have been put on the skin of animals or man, have been
subsequently detected in their bloodstreams.
Bruce Ames has estimated that approximately 1 percent of the
coloring agents in hair dyes are absorbed in the bloodstream each time
a person dyes their hair. Over a lifetime of use this clearly results in
significant absorption from a toxicological perspective. If a hair dye
chemical has toxic properties, we can therefore expect people using
that dye to be at risk.
It has~ become clear recently from scientific studies that hair dye
ingredients do possess toxic properties. Recently, scientific studies
have shown that some hair dye ingredients cause birth defects in
animals and may therefore pose similar risks to humans.
Recently published data shows that a permanent hair dye ingredi-
ent, 2,5-toluenediamine, causes malformations of the face, head, and
ribs from the offspring of mothers who have received a single injection
of this ingredient during pregnancy.
In the second study fetuses of pregnant mice whose skin was painted
with permanent hair dye had a statistically significant increase in
skeletal malformations when compared to fetuses whose mothers were
not exposed to the dye. While these results are not definitive for
PAGENO="0223"
217
assessing human risk, they are clearly a cause for concern considering
the large number of pregnant women who regularly dye their hair.
Moreover, they clearly indicate that industry's claims of safety are not
accurate.
The two positive animal studies I have mentioned. are especially
significant in light of the frequently higher sensitivity of humans
compared to animals to the chemical induction pf birth defects. For
example, humans are approximately 60 times more sensitive than mice
and 700 times more sensitive than hamsters to the teratogenic effects
of thalidomide.
The skin painting study I have described is also of interest because
it was industry study and points out again the problems of allowing
industry to conduct their own safety tests according to their own
protocol and then entrusting determinations of safety to industry's
scientists.
The doses used in the study were clearly below the doses recom
mended by scientific and regulatory bodies for animal teratogenicity
tests aimed at assessing human risk. In addition, despite the statis-
tically significant results described~ the authors concluded without
providing adequate evidence for that conclusion that the results were
not biologically significant.
Hair dye ingredients and hair dyes have also been shown to be
mutagenic in a variety of tests including the Ames test and tests for
mutagenesis, and drosophila, and mammalian cells in culture.
As Dr. Griesemer, from NOT, concluded last week these tests are
highly predictive of carcinogencity. For example, the Ames test has
been shown to corrrectly identify approximately 9 out of 10 carcinogenic
chemicals.
Positive results in mutation assays are also of concern because of the
number of genetic diseases which are apparent in the human popuia~.
tion. Ames tested 150 out of 169, that is, he found that 150 out of 169
permanent hair dyes that he tested were positive in his test. Similarly
most of the 25 semipermanent hair dyes he tested were also positive.
The mutagenic properties of a number of other permanent, semi-
permanent temporary hair dyes have been corroborated by other
scientists and other types of tests. In addition, a number of permanent
and semipermanent hair dye 4ngredients have also been shown~to be
positive.
Phe correlation between mutageni~ity and carcinogenicity has been
borne out by National Cancer Tnstjtute tests. Five currently used hair
dye ingredients are positive in these carcinogenesis bioassays. These
ingredients are used in a majority of permanent hair dyes and in a
number of semipermanent hair dyes. OTFA's claims that these NOT
studies are irrelevant to human risks are unfounded. Although the NOT
bioassays are part of a screening program, they are adequately
scientific to assess human risk. One need not conduct further studies to
justify regulatory action.
Indeed, alimajor Federal regulatory agencies-OSHA, EPA, FDA,
and OPSO-have used maximum tolerated dose studies as a basis
for identifying and regulating chemicals which pose a human
carcinogenic risk.
PAGENO="0224"
218
For example, the proposed OSHA cancer policy states:
* Testing of animals at constant high exposure levels at or approaching the maxi-
mum tolerated dose is not inappropriate and is indeed required to overcome
statistical insensitivity of laboratory bioassays conducted with a limited number
of animals.
Federal agencies have repeatedly used maximum tolerated dOse
feeding studies to regulate chemicals to which people are exposed
through the skin. For example, the Consumer Product Safety Com-
mission has banned the flame retardant chemical Tris on the basis
of an NCI feeding study although the vast route of exposure to humans
was through the skin. Quoting the OSHA cancer policy:
In cases where compounds are absorbed by experimental animals, and circu-
lated systemically, it seems reasonable to regard the route of administration as
irrelevant to weigh the potential risks to men.
Again, two Federal regulatory agencies have relied on these NCI
tests on hair dyes to justify actions. FDA in its January 6 Federal
Register nOtice proposing requirement of labeling and posters in
beauty parlors relied on these NCI studies. Similarly NIOSH in its
warning to people employed in beauty salons also relied on the NCI
findings.
In addition to criticizing the NCI studies, CTFA further claims
that its own skin painting studies demonstrate the safety of hair dyes.
To the contrary these studies do nothing of the kind. The doses used
are simply too small to compensate for the small number of animals.
For these reasons these studies have been criticized by numerous
scientists in the scientific literature.
For example, Bruce Ames has commented that one of the studies
cited by industry could not have detected a chemical that increased
cancer by 5 percent. Five percent cancer rate in the population of
people who dye their hair would be about 1.6 million cancer cases a
year. Clearly safety cannot be determined by an experiment that
leaves this much to be desired.
Moreover, EDF's analysis of the latest industry skin painting study
indicates that even under the conditions used in that assay with mice
where the skin was painted with eitli~r one or two permanent hair
dyes had a higher number'of benign liver tumors of the type that often
become malignant compared to animals not exposed to the dyes. Yet,
industry continues to claim that these studies confirm the safety of
hair dyes.
There has been much discussion of the epidemiological evidence on
hair dyes. It is our conclusion that epidemiological studies do not in
any way contradict these positive animal findings of carcinogenicity.
Indeed if anything, they suggest elevated cancer risk for people classi-
fied as beauticians, cosmetologists, or hairdressers.
In addition to the NIOSH study discussed last week, three other
studies have shown increased cancer rates for people in this occupa-
tional category. No matter what criticisms industry may level at
these studies, they certainly cannot be turned around and held up as
proof of safety.
The committee has already publicly examined the two epidemio-
logical studies held by CTFA as definitive.
The tests done on hair dye users similarly do not indicate the saf ety
of hair dyes. They either have not looked at enough cancer sites or
PAGENO="0225"
219
have not allowed for the necessary period of time to expire between
the exposure to the dye and onset of symptoms that could be detected
in a study.
Dr. HIGHLAND. The evidence summarized by Mr. Dach leaves no
doubt that CTFA's contention that hair dye products are safe is
scientifically unfounded.
The American public deserves something more than unsupported
claims of safety. They must be provided with a regulatory process
that insures that their health and safety will not be jeopardized merely
for the sale of another commercial product. Such a regulatory process
does not exist today.
Mr. Merritt of the CTFA suggested last week that prior to enact-
ment of legislation which would create an adequate regulatory struc-
ture that a National Academy of Sciences panel be convened to re-
view the critical scientific issue.
Such an effort would be pointless and create further unwarranted
delays in the establishment of an effective regulatory process. NAS
panels have looked at these scientific issues before in the cases of
chlordane and hetachiorate, and most recently for drinking water.
They have found that the evidence such as that currently available
on hair dyes is sufficient to trigger regulations to protect public
health and even cause a product to be removed from the market.
New legislation is clearly and critically needed which will require
premarket approval of new cosmetic ingredients based on the evalua-
tion of well-defined toxilogical safety data. FDA must be notified of
the existence of all current cosmetic formulations and any intent to
introduce new formulations into the marketplace.
All health and safety data must be public information and available
to all for critical scientific review. All cosmetics must be required to
carry full and complete labeling information so that consumers know
what chemicals they are being exposed to.
For cosmetics that are currently being marketed, a review of poten-
tial health and safety problems associated with use must be under-
taken. For far too long the legitimate concerns of the Congress, the
FDA, and the public over the safety of cosmetics have gone un-
answered. It is time now to enact legislation to insure human safety
and well-being, and to provide the FDA with sufficient resources so
that this critical area of human exposure to potentially hazardous
chemicals is properly regulated.
This completes our statement. Obviously we will be glad to answer
any questions.
Before I stop I would like to introduce Ms. Anita Johnson who is
the staff attorney at EDF. Thank you very much.
[Testimony resumes on p. 304.]
[Dr. Highland's and Mr. Dach's prepared statement follows:]
24-600 0 - 78 - 15
PAGENO="0226"
220
Environmental.
~ Defense
)IJ)I Fund* 1525 18th Street, NW, Washington, D.C. 20036 * 202/833-1484
January 25, 1978
TESTIMONY OF THE
ENVIRONMENTAL DEFENSE FUND
BEFORE THE
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATION
OFTHE
HOUSE COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE
ON THE SUBJECT OF
COSMETIC SAFETY
OffiCEs *1: EAST SETAUKET. NY (MAIN OPFICEU NEW YORK CITY (PROGRAM SUPPORT OPFIOEI: WASHINGTON OCi SERKELEY, CALIFORNIA; DENVER. COLORADO
P100.0 on 100% R*oycldPapot.
PAGENO="0227"
221
TABLE. OF CONTENTS
58
68
72
75
77.
82
1
4
25
31
37*
Introduction
Chemistry and Use of Hair Pyes
Absorption
Mutagenicity
Animal carcinogenicity
Epidemiology :
Teratoger~icity
Regulatory Authority.
* Proposals for Legislative changes
* References * *
Appendix A
PAGENO="0228"
222
Introduction
Good Morning. Mr. Chairman, members of the Coimoittee, I am
Dr. Joseph Highland, Director of the Toxic Chemicals Program of the
Environmental Defense Fund (EDF). With me today is Leslie Dach,
Science Associate at EDF. EDF is a non-profit, publig interest
group with over 45,000 members that has long advocated elimination
of unnecessary human exposure to toxic chemicals. In May and again
in September, 1977, EDF testified before this Committee on the
regulation by the Consumer Products Safet~ Commission of the flame
retardant Tris. In October 1977, EDF petitioned the FDA to require
all hair dyes containing 4-methoxy-m-phenylenediamine (4HMPp) to
carry a label warning consumers of the cancer hazard posed by 4MZWD.
FDA proposed regulations accepting this petition in the Federal
Register of January 6, 1977. In comments submitted to FDA on January
11, 1976, EDF has also asked that the provisional approv~l for the use
of the color additive lead acetate in haiz~ dyes be terminated. Lead
acetate causes cancer in animals and has been shown to penetrate the
skin.
We are here today to discuss the health hazards posed by
cosmetics. Over 7 billion dollars worth of, cosmetics are sold each
year. Currently there are over 24,000 different cosmetic formulations
containing about 8,000 ingredients. Each year this number increases.
This amounts to about 9 billion units a year, or 45 units for each
1/
man, woman arid child in America. Thus, the American people are
exposed to thousands of cosmetic ingredients, ~ngredients about which
we have little, if any, health effects information. We simply don't
PAGENO="0229"
223
know what these chemicals can do to people. Nor, given the prosent
stacuatory ar.ci regulatory situation, are we likely to find out.
FDA cannot require manufacturers to conduct safety tests. It can't
even demand to see the results of tests, no matter how shocking they
may be, no matter how many consumers may be hurt. And FDA claims not
to have the resources to do the tests themselves.
We can expect many of the chemicals in cosmetics that we put on
our faces, hands and heads to enter our bodies. Some, like hair dye
ingredients, absorb through the skin. Others, like lipsticks, are
ingested. Thus, toxic cosmetic ingredients can be expected to cause
illness and perhaps death among consumers. We needn't here repeat
the gruesome statistics that describe the cancer epidemic in America,
or the portion of those statistics that can be attributed to environ-
mental causes. What needs emphasis is the responsibility of govern-
ment and industry to minimize exposure to chemicals that have the
ability to kill us.
The Cosr~etics, Toiletry and Fragrance Association (CT?A), the
trade association representing industries which sell about $300 million
of hair dyes a year, tells us that cosmetics are safe, that there is
little reason for concern. Certainly, they cannot claim that they
have tested even a small proportion of cosmetic ingredients for
safety. And to claim that the evidence to date reveals no substantial
hazard merely emphasizes the lack of safety testing currently under-
way. Furthermore, contrary to CTFA's claims, scientific evidence
developed over the last year clearly shows that cosmetics pose a
number of serious health hazards.
PAGENO="0230"
224
For example, scientists have recently shown that N-Nitro-
sodiethanolaisine, a compound known to cause cancer in animals and
a member of a family of compounds (the nitrosarnines) that are potent
carcinogens in all species looked at so far, is present in a wide variety
of skin care products, shampoos, lotions, and cosmetics. Another
example -- and this brings us to the focus of our testimony here
today -- is the National Cancer Institute's (NCI) recent findings
that 6 hair dye ingredients cause cancer in animals, and thus pose a
presumptive carcinogenic risk to humans.
PAGENO="0231"
225
Chemistry and Use of Hair Dyes
About 33 million American women regularly dye their hair. This
figure represents nearly 40% of all women over the age of 13 and
almost 50% of women ovet 40 years old. Consumers spend over 300
2/
rAillion dollars a year on hair dyes.
The vast majority of hair dyes are known as coal tar dyes,
because the dye chemicals used to be derived from coal tar, tar
obtained through distillation of bituminous coal. A small propor-
tion of dyes use metallic or vegetable colors. In the following
discussion we will focus on the coal tar dyes.
A number of companies market coal tar dyes. These include
* Clairol, Cosmair, Alberto Culver, Revlon, Redken, Toni, Ozon, and
Helene Curtis. Clairol, a subsidiary of Bristol Myers, has about
* 70% of the U.S. hair dye market. Cosmair's subsidiary, L'Oreal,
has about 15 to 20%. About 12 to 15% of Bristol Myers' U.S. profits
3/
derive from sales of Clairol hair dyes.
There are three types of coal tar dyes. Temporary hair dyes
or color rinses are used to add highlights and brightness to natural
color, improve shades of grey hair, and blend unevenly-colored hair.
The first rinses were introduced in 1922, and were patterned after
4/
similar products used to color textiles. Itinses are usually
applied to the baàe of the hair, and combed through to the ti~p. The
dyes are deposited on the hair fiber and usually do not actually
penetrate the fiber. Thus they wash out during shampooing. The
desired color is obtained through the use of a mixture of colored
chemicals. The chemicals used are acid dyes of the type used in
PAGENO="0232"
226
-5-
5/
wool dyeing (see Figure 1).
* 0 NH__QCH
OcJi -
Aod Vic~et 43
HO3S..ONN)~fll~00H
SOH
Tortrazre
(yeilow)
The second type of dyes, semi-permanent dyes, last a bit longer,
wearing off after sevexal shampoos. They are.often used to blend
streaked hair, to improv~ the col~ring of white or gray hair, or to
acid highlights to naturally blonde 1~air. Again, the desired shade
is acheived through use of a combination of dyes. The chemicals
used are usually aromatic airines, such as nitrophenylenediames, and
aitroaminophenols. Typical dyes and their colørs are shown in
Table 1. Semi-permanent ciyes are usually applied to hair in a
shampoo base for 20-40 minutes before being rinsed out.
The most widely-used dyes, accounting for. about 75% of the market,
are the permanent dyes, first introduced as a standard commercial
product in 1910. The dyes use small, colorless, low molecular weight
chemicals, usually aromatic aniines such as 2,4DAA, which penetrate
PAGENO="0233"
227
Table 1
6/
~es Used in Semi-Permanent Nair Colors
Chemical Name CTFA Dictionary Name Color
2-'Nitro p-phenylenediamine 2-Nitro-p-phenylenediamifle I~ed
4~Nitro-o-phenYleflOdiamine 4-Nitro-o-phenY lenediainine Yellow
2-Amino- 4-nitrophenol 2-Amino- 4-nitrophenOl Yellow
C.l. Acid Orange #3 Acid Orange #3 Orange
the hair shaft. They are then oxidized by hydrogen peroxide into
larger, colored molecules which become locked inside the hair. The
resulting color is not removed by shampoo, and monthly dyeing i~
generally needed only to color new hair growth.
In addition to hydrogen peroxide, two types of dye chemicals,
are used in permanent dyes, primary intermediates and couplers, to
give the desired color. These dyes also contain other components,
including stabilizers, detergents, anti-oxidizers and alkalizers.~
The primary intermediates are usually ortho or para aromatic
diamines or para aminophenols. Present in excess amounts they are
oxidized by the hydrogen peroxide to reactive intermediates which
yield colored products when joined with either unoxidized primary
intermediates or couplers. The couplers are usually meta diamines,
mets aninophenols, mete phenols or pyrazolones. 2,4DAA, for example,
is a coupler.
In a typical hair dye reaction (see figure 2,page 7) with
2,4DAA, the primary intermediate, for example paraphenylenediamine,
is oxidized to form p-benzoquinone diimine. This diimine reacts
with 2,4DAAto give a triaminodiphenylarnine, which then undergoes
oxidation to the 2-aittinoindamine dye. The indainine dye is a
violet-blue color.
PAGENO="0234"
228
Figure 2
NHL NH OO4~
-~r~---> () ÷
NHz NH
?AMP~ENYLNEDW~ VASZ~nr~ONEDUMP4E 2'~ DM
N~cxN2c~L
Z.PMINO%NDAM~NE T~AOPHEt'~YA~1N~
Because a typical hair dye oontains several couplers and primary
intermediates, numerous colored dye products are formed. The combina-
tion of these products dtermines the final shade.
The hair dye chemicals identified as carcinogenic by the National
Cancer Institute are used in the vast majority of permanent hair dyes
and a number of semi-permanent dyes. Based on information supplied
to FDA by industry in a voluntary registration program, over 400
permanent hair dyes contain 4MMPD (2,4DAA) or its sulfate salt (see
Table 2 ). About 300 permanent or semi-permanent hair dyes contain
2NPPD or its sulfate salt (see Table 3 ). Over 70 hair dyes list
PAGENO="0235"
220
4A2N1 as an ingredient (see Table 4). The Government Accounting
Office (GAO) reported that 7 temporary dyes contain Direct Black 38
8/
and one temporary dye contains Direct Blue 6. Because the voluntary
registration may i~ot result in FDA's having a complete list of hair
dyes containing a given ingredient, the numbers cited above may be
short of the actual number of products containing a given ingredient.
* Regardless of the exact total, it is clear that the vast majority øf
hair dyes contain at least one cancer-causing ingredient, ax)d that
* therefore the vast majority of ~33 million Americans are at risk.
PAGENO="0236"
L1Oroal Preference Salon Formula
Blue Black
Ddrk Brown
Datk Ash Brown
Medium Brown
Medium Ash Brown
Light Brown
Light Ash Brown
Dark Ash Blonde
Medium Ash Blonde
Ash Blonde
Light Ash Blonde
Dur~ished Copper
Reddish Blonde
Lighter Gold
Light Reddish Blonde
L'Oreal Preference Permanent
Crerse-In Nair Color
Blue Black
Soft Black
Dark Brown
Dark Ash Brown
Nadium Brown
Medium Ash Brown
Light Brown
Light Ash Brown
Dark Ash Blonde
Ash Blonde
Light Ash Blonde
Extra Light Ash Blonde
Lightest Auburn
onde Auburn
Medium Ash Blonde
L'Oreal Drabber Moonlight
L'Oreai~ Drabber Moonmist
L'Oreal Excellence
Permanent Flair Color
Blue Black
Dark Brown
Medium Brown
Light Brown
Light Ash Brown
Medium Ash Blonde
Ash Blonde
Light Ash Blonde
Very Light Ash Blonde
Natural Black
Deep Ash Brown
L'Oreal Preference
Perfect Blonds
Light Beige
Soft beige
Perfect Platinum Ash
Perfect Deep Ash
L'Oreal Super Blonde Toners
* Super Light Beige
Super Soft Beige
Super Platinum Ash
Light Platinum Ash
Silver Beige
L'Oreal Excellence Permanent
Shampoo-In Color
* Blue Black
* Dark Brown
Medium Brown
Light Brown
Light AshBrown
Deep Ash Blonde
Medium Ash Blonde
* Ash Blonde
Light Ash Blonde
Very Light Ash Blonde
Burnished Copper
Platinum Ash
Tawny Ash
Frosted Beige
Natural Black
Deep Ash Brown
Soft Ash Brown
230
ABLE ~
L'Oreal Young Blonde Ash Gentle
N~T~Li~htener
PAGENO="0237"
TABLE 2 (continund)
L'Oreal Excel'enCe
Creme Sh~uspoo Color
Blue Black
Dark Brown
Brown
Light Drown
Light Ash Brown
Deep Ash Blonde
Medium Ash Blonde
Ash Blonde
Light Ash Blonde
Pearl Ashene
Extra Light Ash Blonde
Extra Z~ight Beige Blonde
Platinum Ash
Tawny Ash
* BeigeArgant
bark Ash Brown
Medium Ash Brown
Dark Drabber
* Light Drabber
Miss Clairol~ Hair Color Bath
Arctic Blonde-
Autumn Mist
Berrywood
Black Azure
Black Velvet
Blue Black
Chestnut Brown
Coffee Brown
Ermine
Flame
Flaxen Blonde
Golden Apricot
Mazy Mist
Money Red -.
* Lt~ Smokey Ash Blonde
Medium Smokey Ash Blonde
Moongold
Moonhaze
MooBlit.-BrQwn----- -
Red~Oak
Sable Brown-~
Soft Mist
Starlight
Suntlonde Brown- - -
£u~iJ.t. BrowA_
Sunset Brown
Sunny Auburfl
Topaz
Winter Wheat
Clairol Nice and~
Natural Ash Brown
Natural Black
Natural Blue Black
Natural Dark Auburn
Natural Dark Brown
Natural Deep Auburn
Natural Light Ash Blonde
Natural Light Ash Brown
Natural Light Auburn
Natural Light Beige Blonde
Natural Light Brown
Natural Medium Ash Blonde
Natural Medium Brown
Natural Pale Ash Blonde
Natural Pale Blonde
Natural Tawny Auburn
Miss Clairol Shampoo Formula
Autumn Mist
Black Azure
Black . Velvet
Chestnut Brown
Coffee Brown
Coppertone
Flame
~Flaxen Blonde
Go),den Apricot
Moongold
* Moonhaze
Noonlit BrOwn
-Red Ginger
Sable Brown
Sparkling Sherry
Sunbronze
Sunlit Brown
Topaz
Winter Wheat
Miss Clairol Creme ~`ornula
Arctic Blonde
Autumn Mist
Black Azure
Black Velvet
Chestnut Brown
Cof fee Brown
Coppertone
Ermine
Flame
Flaxen Blonde
* Golden Apricot
Money Red
231
.1
PAGENO="0238"
232
TABLE 2 (continued)
Miss Clairol Crerne Formula
(Cant' d)
Moongold
Cherry Silver
Moo~haze
Moonlit Brown
Sable Brown
Sparkling Sherry
Starlight
Sunblor~de Brown
Sun Bronze
Sunlit Brown
Sunset Brown
Sunny ~uhurn
Topaz
Winter Wheat
Clairol Balsam Color
Ash Blonde
Auburn
Black
Dark Ash Brown
Dark Blonde
Darkest Brown
Golden Brown
Palest Ash Blonde
Palest Blonde
Light Brown
Medium Ash Brown
Medium Golden Brown
Light Ash Blonde
Clairel True Brunette
Light Golden Brown
Medium Ash Brown
Medium Brown
Dark Ash Brown
Dark Sable Brown
Darkest Brown
Deep Reddish Brown
Black
~ç~~p~nde
Completely Beige
Completely Flaxen
Completely Honey
Completely Platinum
Completely Towhead
Clairol R~d Fashion
Cherry Silver
Pink Silver
Sun Silver
Clairol Naturally Blonde
Autumn Ash
Cool White
Dusky Fawn
Evening Ash
* Fair-Haired Blonde
Natural Pearl
Opaline Amber
Opalina Ash
Opaline Beige
Platinum Breeze
Platinum Surf
Sifted Sand
Silver Treasure
Softly Blonde
Sumner Haze
Sunny Beige
Sun Touch -
Swedish Crystal
Swedish Taffy
Truly Beige
Willow Blonde
Clairol 5-minute Color
Black
Blonde
Dark Brown
Light Brown
Medium Brown
Cool Ash
Dark Ash
Gentle Platinum
Golden Blonde
Light Beige
Light Platinum
Lightest Blonde
True Beige
Whisper White
White Platinum
Lady Clairol Lady Lights
Golden Whisper
Hazy Honey
Honeysuckle Blonde
Moon Beige
Moonlit Ice
Spun Honey
Starlit Sand
Touch o~ Taffy
Clairol Futuretone Non-Asn~o~ia Toner
PAGENO="0239"
TABLE 2 (continued)
Clairol Creme Toner
Baby Pearl
Blush Pearl
Champagne Beige
Champagne Ice
Champagne Parfait
Champagne Sherbet
Champagne Toast
~xtra Light Platinum
Honey Chiffon
Ivory Chiffon
Mood Mist
Platinum Beige
Silver Beige
Silver Platinum
Sterling Pearl
Sunshine Flonde
Tan Pearl
White Beige
Breck Hair Color
Dark Brown
Palest Blonde
Ultra Light Blonde
Medium Ash Blonde
Dark Ash Blonde
Light Ash Drown
Medium Brown
Natural Black
Clairol Sal c~Srunettes
- Light Golden Ash
~edium GoldenAsli
Dark Ash
Light Smokey Brown
Light Golden Ash
MediumSmokey Brown
Darkest Smokey. Brown
Helene Curtis Coloressence Creme
Hair Color
Light Drabber
Dark Drabber
Light Ash Blonde
Ultra Light Ash Blonde
Pastel Blonde
Medium Brown
Light Brown
Dark Brown
Dark Ash Blonde
Dark )~uburn
Light Auburn
Black
* Medium Gold Brown
* Helene Curtis Ultra Coloreseence
Creme Color
* Baroque Black
Sunburst Brown
Light Drabber
Ivory Blond
Heather Blond
Autumn Blond
* Gossamer Blond
- Keavenly Brown
Pecan
* Helene Curtis Ultra Tone Creme ~oner
OzonCreme Color
Rich Light Auburn
* Rich Light Brown
*Rich Dark Brown
Rich (Lig1~t Drab Toner)
Rich Dark Drab Toner
* Rich. Light Golden Brown
Rich Dark Drab Blonde
Rich Black & Blue Black
* Rich Real Copper
Riøh Medium Brown
* Rich Bright Red
Revlon Colorsilk
Light Ash Brown
Medium Ash Blonde
Medium Warm Brown
233
Clairol Sunn~er Blonde Lightener
Frosty White
Whisper Blond
Miriam Collins
Hair Dye Blue Pearl
Hair Dye Stardust
Tones Exotic Lite Silver Blonde
Toner Gardenia ~Beige
Toner Honey Dew Beige
Toner Moon Light ~lon6e
toner Pearl Platinum
PAGENO="0240"
TAL~I.~ 2 (cor~tinu~a~
ion Colorsilk (cont'd)
Medium Drown
Light Brown
Pale Ash Blonde
Dark Ash Blonde
Strawberry Blonde
Medium Ash Brown
Medium Dark Brown
Dark Brown
Brown Black
Black
Blue Black
Revlon Younghair Natural Color
Toner
Medium Smoky Brown
Light Smoky Brown
Dark Smoky Brown
Light Ash Brown
Medium Ash Brown
Laght Brown
Dark Brown
Black
Smoky. Blonde
Natural Medium Brown
Redken Custom Cretne Colour
Sable Brown
Ebony A~h
True Ash
Dark Blonde A~h
Crane Blonde
BlOnde Ash
Lightest Blor.de Ash
Ultra White Silver
~Ultra White Blonde
Redken/Lapinal Amino Color
Dark Golden Brown
Nedium Coide~ Brown
Dark Natural Ash Brown
Medium Natural Ash Brrwn
Light Natural Ash Brown
D~rk Natural Ash Blonde
Medium Natural Ash Blonde
Lightest Natural Ash Brown
Rodken Drabber
Smoky Blonde
Blue Lady
COLOR RINSES AND SEMI-PER~1ANENT
HAIR DYES DO NOT CONTAIN 4-MMPD.
234
* Redken Hair Toner
Silver Platinum
Blue Snow
Sterling Silver
Redken Tender Toner Hair Color Creme
Creme Mauve
Pearl Platinum
Honey Mist
Redken Pastel Poner Hair Color
Ultra Light Platinum
Toni Hair Color for Innocent~
Black
Light Brown
Medium Brown
Dark Brown
Pale Ash Blonde
Ash Blonde
Light As1~ Blonde
PAGENO="0241"
235
~NN~N~
I I
Z~~I I
Ii I
I ~
~ ~ ~
~I.
24~6OO 0 - 18 - 16
PAGENO="0242"
TABIE 3 (contilsuod)
HAiR OYE PP000CIs
CoNToFNI~o
_ - - CBS NO. 005307147 BPI0040_P_PHOLENEOIAMINE -
NIT P_?VYLFNIUIAMIPAI
R4ANY HAYES
01/19/78-
*
CPIs
HUMMER
- - - - -- - - CBS
*
~
*
- -
CLAIROL INC
F0035059
EOO35060
F0035079
FOO3SRMR
FOO350~g
F0035168
F4035]73
P0035174
P0035176
F0035107
F00351R)
F003516s
FOT3SIFS
MISS CLAIROL SHAMPOO FORMULA BLACK AZURE - 5?S - - - -- - 005307142
NICE AND EASY NOTUIOAI MLti BLACY 174 005307142
TRUE BRUNETTE LEER REODI5HPTROWN - - 005307142
bobs CARE P-FAIR COLOR 100105 jR~;coj
00570714?
GREAT 5Ay LIGHT RLDIUM OPOAFA -----------005307142 -.
GREAT DAY DOOR RAVo,. (JLACO - 00530714?
MISS CLAIROL HAIr COLOR BATH ELOPE - - -- - - *~__~ ~*__ 0O5307I~
HISS CLAIROL HAIR CP-;LUR PlATO-I COP O-TG1E 00030714?
HISS CLAIROL HAIR COLOR BATH 5PARGLING 500IRRY - - - - 005307142
MISS CLAIROL HAIR COLOR BATH RED CIGSEP 005307147
RED 0050100 FIRL SILVER. - *~ -- ~~~~0053o7L45*
RED FASHION SiN SILVER 005307142
RED FASHION PINK SILVER - -- - -- - - *-__ - ----__-~~ - - - -- 0TS3u7l4~
CEO FASHION
*
P00351MB
P0035193
- P0035194
P0035190
P0035199
F00352OT
-
sItvrR 005307147
FIVE MINUTE COLOR AG-TURN --*-__* ---_- --__**__~ - ------__ ---00530714?
GlEE AGO EASY NATURAL PALE 05H 0105SF 00530 7142
NICE AND EASY NATUTYVL LIEU-iT HE 151
NICE ASS EASY NATURAL ISA 600RN 0O53O7l~.?ç-
NICE OTTO EASY NATURAL ROLE EUOrrcSE - - - - - - -- - - - - - * - -- - - 000)0 7147
NICE ASP) PA5~
P0035751
PIATUPOL LIGHT ASH YTOPiDE 005307142
NICE AND EASY
- - -
P0035707
F0O35203
P0035704
NATURAL OFOLUEN 6LONOE - - - - - - - - - ------ 005)0714?
NICE AND EASY NATURAL MEDIUM ASH ALOSDE bOS3G7ISY
NICE ANT EASY NATURAL REDDiSH BLONDE ~-~-----OCS307042__
NICE A~4D EASY
P0A3570,S
NATURAL LIEU-U AUUJRN 005307142 -
NICE AND FAST
*
P0035701
NATURAL OARs AUBURN
- - - - -- - - -*- - - - --_ 0OS307I~7
P-lICE ASS EASY
P0035707
NATO-PAL LIGHT ASO P0005 005307142
NICE AND EASY
~.
P00302DB
- FAO3S?o9
P0035226
P0035227
NATURAL LIGHT BOORS - - - -- - - - -- - 005307142
GilL AND EASY FJ0TIRRL MFDIUP- RVORs 005307162
NICE 051) EAST NATURAL 000o RROWN ~ -_--_-0IS307142 -
CAERE TONER COOARPRGNE BEIGE 005)07142
COOERE
-
P0035720
SILVER BEIGE - - *~ - - -- - - -oooooiio.~
CR101 TONO-io
P0035231
ROTE BEIGE - 806307142
CUbE TONEP
P0035237
- - P0030234
P0035235
HONEy CoIFFOs - - - - ----*--- - - - - 00530714?
CRLAE TONER i'FACiO CHIFFON 005307142
CRIME TOIlER CAIR0000GI ICE - -- - ~
CAERE
F003523N
TONER CIPRAPASGE SACARET 005707142
CAERE
*
P0035737
TONER C000PAGNC PARFAIT - - - - - **~ -- - - 000307142 -
CRIME TONER
P0030744
TOAST 005307142
NATURALLY
- -
-
FF030245
P0035746
310551 PLATINUM SURE - - - - -- - - 005307142
LAGY CLAIROL ENVY LIUHOS 0005 BEIGE - - 814 00530714,
HOPJPALLT MlT'TUE NATURAL HO AOL -- - -- ~--000o7042_
COMPLETE RLONSE
*
COMCsF TELl 00511 115 000307142
LADY CLA100L
.
LIE-ABS AOi3O5UCYLE BLONDE 012 - 005307142
PJATTJRBLLY
-
P0035247
-
lAITA-MAIRLI) 01091)1
406 - 00530714?
COMPLETE RLO~D)E
- - -
.
-
*
- -
-- -- - -
P003524$
COOPLETELY RE 16 167 - - - - - 00530 7142 -
LADY CLAIROL EAQY LIYRTS 5PUN HONEY Alt
005307142
NATURALLY ELOIADE GUTSY REbEL -- -. - 457 - ---- 0053071&2 --
1000 CLAIROL LADY
-
-3020 HOlly 018 0003A7142
NATURALLY BLONDE TALLY 01161
PAGENO="0243"
TABLE 3 (continued)
01/19/70 - HAIR DYE PRODUCTS
* CONTAIN~ND
*__._SSS5......_SS.SSSSCAS NO. 0R5307142_2-N1TPDP-PHENTLENEDIkMINE~__
RITRO-P-PHENYLONFDIAMINE
OPIS - - BRAND NAMES S.- - - - ---_-.--. - -. .- -- CÁO - -- -
* NUMBER -
CLAIROl. INC -
#0035250 COMPLETE BLONDE COMPLETELY TOWHEAD - -- 161 -. * __--- ----------- ------------ - --- -005307L42 --
- 1Aç>Y CLAIROL LADY LIC$TS TOUCH OF TAFFY - 822 5 005301142
* - - NATURALLY BLONDE SIFTED SAND -. 410. - ~~__-__- __~-_ ~_ 0OS307l4~
#0035251 COMPLETE BLONDE COMPLETELY ASH BLONDE 163 - 005307142
.S__LADY CLAIROLLAQY LIGHTS STARLIT SATAD_ 824_____~ 00530744?--
* NATURALLY BLONDE SWEDISH CRYSTAL 411 005307142
#0035252 NATURALLY BLONDE AUTUMN ASH - - _:.____-__------------- *-----------005307142
#0035253 NATURALLY RLONOE EVENING ASH - 005307142
- - - #00-35254 NATURALLY BLONDE 00512 FAWN - - - ~_~___-- - ___------------~~--- -~ -------- 005307162
00035255 NAtURALLY RLOFAUE SOFTLY BLONDE 005307142
- #0035256 NATURALLY BLONDE SUN TOUCH - __.__~ - 005302162 -_
- #0035257 NATURALLY BLONDE AItLOB OLONDE - 005307142
- #8035255 NATURALLY BLONDE 8LONDL GLOW ____________~ ______ 005-307162-
#0035259 MISS CLAIROL HAIR COT_OR OATH SUNLIT BROWN 5 005307142
- #0035260 MISS CLAIROL HAIR COLOR OATH POOFALII BROWN. ~ _.___ .._____._-_--_-_---------~-~~--~ 005307142
10035161 MISS CLAIROL HAIR COLDS BATH WiNTER WHEAT - 00G3G7C42~
F0035262 MISS CLAIROL HAIR COLOR BATH SPRING HONEY___S.___. - - _fl053OZlA2i-~_.
* #0035263 MISS CLAIROL AlP COLOR BATH AUTUMN MIST 00S307i4?~
#0135204 NATURALLY BLONDE OPALINC AMBER - _!_________________~_~_~_______.___00G307142L
#0025265 NATURALLY BLONDE OPALINE -BEIGE - 005307142
#0035266 NATURALLY BLONDE 0PALINE ASPi ~ __---------005307042
#0035267 MISS CLAIROL CRETE FORMULA ARTIC BLONDE - 00530714?
- - . #0035268 MISS.CLADROL CRANE -FORMULA HONEY ALO 029 - ~_..i1lS3OX142__
MISS CLAIROL HAIR COLOR OATH HONEY 740 - 029 005307142
- #0031269 MISS CLAIROL CREHL FORMULA SUNNY AUBURN - _..~_.-031
MISS CLAIROL HAIR COLOR BATH SUNNY AUBURN 031 00530?L42
- - 10035)55 NATURALLY BLONDE SWEDISH TAFFY - - ___~__________ S_S _______SS 005307142
#0035411 MISS CLAIROL HAIR COLON MATH HONEY RED 005-307142
#0135412 MISS CLAIROL HAIR COLOR MATH SUNNY AUBURN 00510714Z.__
#0035424 MISS CLAIROL CREME FOJOp(JLA SUNYILONUE BROWN - 00530714?
F6135425 14155 CLAIROL CRANE FORMULA SUNSET BROWN - ~ 005307142
-#0035427 FUTUTETONE NON AMUDFTIA TONER OARS ASH 005307142
- 10035428 FOTURETORE NON 0MMONIA TONER COOL ASH - --- - ------ _~------------------ 0~S3G~1~2 - -
F0035429 IUTURETDFAE HON AMMONIA TOWER LIGHTEST BLONDE - 0053*7142
- #0035430 FUTURETONE NON AMMONIA TONER OOLDEN OLONDE.__S._ 0~S3O7142_-
10035431 FUTUAFATSONE TON AMMONIA TONER LIGHT BEIGE 005007142
- 1003541Y EUTLIRETONE NON DM40514 TOOlER TRUE BEIGE - - -_-_--- ---- - -- *----- 005301142 --
10035453 MISS CLAIROL HAIR COLON MATH S(TNSCT BROWN 00-5307142
10035450 MISS CLAIROL HAIR COLUY-( BATH SUFBLONT)E BROWN - - - - -- -- __*_. ____-_--_---- - ___- 005307142--
F0035517 MISS CLAIROL HOER COT_OH BATH LACTIC BLONDE 005307142
-- - #0035534 FUTARTETONE NON AMMONIA TONER OEPiTLE.PLATlNUN____.___-___._--~ - - ____~_0053I714Z---
#0035635 FUTUPETONE FIGS AMMONIA TONER ROISTER WHItE * - * 005307142
#0035545 MISS CLAIROL HAIR COLOR BATH PEORYW000 - - __-- - - 005300142
F0035S52 M155 CLAIROL HAIR COLOR BATH DID (TAR 005307142
- #0035553 BEAUTIFUL BROWNS CEDAR-RED BRYAN S - -- ----- - -- - - ------ 005307142
F053556' BEAUTIFUL OPYRNS OYSW000 140DM 005301142
FOO3T5(l NICE AND FAST NATURAL 1AROY AUBURN 111 -- _ __.____- _
* F0035S~2 PICE AND FAST NATURAL DEER AUWIS~UN 005357142
P0*35569 FYDOUSLTCOIE ND AMMONIA TUOOA SOFT STRAWBERRY - - 005307142
PAGENO="0244"
Tz~rJJ 3 (cer:tir7ucd)
01/jR/IA - - s*Io url IH(h:;JCTS .. - .. ~. -- -
- _. COO HO, 009397162 ~-S11-P-v1fN0uJ*HI6t._~_
On IR3_1_P#~EL1t0IrILRI.~t
COIS bOL9U 880(5 - - - ... 1. - . . coo
88119
CLAIROL 11.0
F u095575 8159 (17140'. HaIR 001CR BATH RLO?C-FST GOLD - . - - .--.-- ~- -- .---- .--..- 00593174/
1753.574 HISS CL87~n1 `~AIR ~0t0 f0)~ (83n7r)551 IfIrl 0053371.-
F1O3~-~i 15755 CL'!~-L (~1E I n'nj7 A I fAt 511518 - . -. . - . . --. -- 009th...
~355r9 `155 01*1~11 CA[H~ IC4~n.tA C0R~o 511410
10031129 R05S&a C/TSR ~ f(.Af ~ 010501 - .. ___.__ . ___________________-----
10035702 51.01 F;"i-t OTIS 1IG~9 GOLLIP ASH 003 00535714
0003570o 1-3s5 CL'lAOL HAIR CCLOi4 6110 &LU-OLICA Si ____~_____~-. - 00~7jii4
Fc53575~ CAErE 11.10 0000 FIST 33' 0053077
11035709 CR11-C Tt~fP SU?4SIIOE 8101.00 334 - ----- ------ - - ---- --- - - 000)oll.-:
COSMAIR fEC
10010300 tOFLAT tFCEtI0650 COORS 5820050- COLOR 6.1 1151 ASH IROOH__.___ -. ._~~~00S)07L1.
L'tO'EEE. E':U.LEhCE IA~(L7T 807* COLCO to t ic-it Iso -OOwW . - 0011.0071..
L'O~ AL ICFIIEPI.1 P0k'ot'rT s.o'4n-o~ In COnCH 65 LIGhT 1517 800oN - - ____~~___ - 0003071-..
100)9321 (`00081 OXCILLCSI ~ so~0C COLt 7.1 0F7~ A~ 81.0101 0003070':
1'O~1oL FCIIL(61 RfoA4~T c-lOGO 1 COLO- To 0% 14- 05H E0oHIlt. - - ._____ __~____ 0013010%::
15019302 (`nISAI. t0-CL11PO1 COOP-I Sh~-Pc-0 Cl-IC-S 7,15 013111 ASPI 001n.%1 OAloJcIl'-2
-- - .. I'oOCAL 11.1110%-Cl fE4'lILIT *I° COIlS 7 1//A ~It}1Lo-T ASH BLOIrOL_ -.__________________ . 005107142
(`00701 IoCItl*#SC P -~1NT 5158--OS In Cn0GH 7 1/4 A 81011)1 AS-I 61000 C00i714/
10019393 I'S-ALAl loClziLSCL (`1150 515015035 IOLCA 0.1 ASH Is003L - _______ - 000307142
1'OOEOI 11(0701 110000107 rsI° CoLt? HA 0511 1.1.5/1 00514114?
(`001*1 I'CCILIP.CE VHon.'rt 51o1-ç-~ IS COLCo PA 151 HLCP-IO( .. ._________~_~. 035307747
10019304 1'O-'EOL 110(ILOPCE CAP-PIE SHAH'0O COLOR 8.11 04.-IC-SI BLOSTlE 00530714
.- - - 1'O~1AL EYC(111N01 1181-'AnLPr! 081* COLOR 6 I//A 0808781.57 IIL000E_._ ~- 00530114
100071 O'C'IIESCE P041451ST S-4A~7-c-3 So CC,nc0 6 1/2* (15*51580771 SLOHOC 050)C71-
10059365 L'O~tot. 0000LL(P4/E CAll-pt 5-008 r~ 00100 9 080111 5c-& - ... - - _ - .o_.__ - - _. -- ~. ~C533l74
IOAIAL I000(LCo.01 P(ObRn78n1 I `1~ COO 9 PASTEL E'.~51n( 1053071~ -
- L'081*L EoCtLl0%-C1 PE6'nAoIst 500*700 717 COIL-n I 705111 IL040C -- .___~._______ _-_ 00530710.
10019306 LOOP-AT.. 1/CF11ISCL Cr100 coA.-A53 CO1O~ 9.1 11100 ASH 61.0101 0C33C714~
- -- l'OPIAl E'TOLLIT/L FCPrur0T 8013 CDLI-- 9* 110111 0SHILO::OL__
- 1000*1 toCILTEsCI 10800SnSI 5TLr3~0O fIn COLcA 98 LIGHT ASP Buo*OC 0-053-70%-
100)9307 ~0:11tL (/01111601 Cl-I-I Solo-eD 0/1.009.1016101 8681111 - - __ __-__--- 00530714.
- 10*781 E'~LL1~Ct CFL~1 5157HPC~ 10104 9.IuA 1915 LIST ASP 610101 - 00010/1':
- (`00(01 (051111-401 1-t0.-A:4151 01* CO1~'3 9 1/00 vOl-p 11007 ASH 0101-31 - ~~__._ - 00037744
* t'O(OL 71017(14(1 11 --o-n1'-nf 5~A"?0O 1w (1104 5 I//A VOPY LIGHT 0511 01 005337)c
10019308 L'OE;L (,C~L11NC1 011151 SATA-0030 C/LC~ 905 (oTIs LI0151bLl&C0L0-IEaC ______________________________-00530014L
10719359 L'OSt*L 7711111011 C01~-L ~(La?55 0014l- 4) (&~o In~lAN 0003-371'
* - - - LOPC0L (P011115(1. II ~MIIntii1 8*10 10t00 41 0A44 *t;sjoPi * __ ~_-. 01031714
100C01 (1011114(1 610010111 500090/ 14 COLCA 46 SARO AUBURN 03~3Ch1'r
18019310 1001*1 ErlEtlTrrCt CAb-I 015715200 (0100 43 610 IIP-cy - - _~_ ._____-__-_-~------ 401.30114/
1'OQ( *1 110CO1IP.C1 IIA1ASET.1 5085100 II: (0/1007 70 410) PE#P*Y 005301141
1001931L L'0El~ 1/11111011. CrIol S0A~25) 1011.0 64 110151 013089 --000111714?
- L'IIOIIL (`01111011 0L8571lnT 010 COLOR 77 11401 AT/HURlO 005371142
L'00111 110(1(1801 114°R*SLI01 515120,0 IN COLtS 62 IbAro At700RN - - -_- -.------------ 005 107142
* 100193(2 (`1.71*1 1/CILILl-CI 71800847 SOARP0Q IN Cr3108 11 500041515(0 Cul-PER 000117147
: 10)19313 1'O1EAL 1*017 11901 CHERT S-A*000 CCLO7 8.3 0018114 P-L0~0( -~-------- --. --- -. --- 0*5307142
l'oo*C 100IILIP.C1 PC-AASLOT 00*1100 Is (0104 73 1-111-114 PILOtrUC 005307142
1(019314 L'C°EAL t'01111011 CPCPIE $A~25Q IfliOR B.'. 011-olSo 510~*O1 - -_-__- ~- ~- -~---
(`001*1 (1(111011 11*01,641 58*15000 111 COLOR S~0 410)150 8107100 005327142
- (00)9315 L'O'L*Ll/ClllLrC( COIPIC SH*IPOO (-010~4 010057 01IS~J~~~, ~ ~__._.-15_-____
PAGENO="0245"
TABLE 3 (continued)
Co
-. *1/19fl8 . *
- -- - -*---,*---- --- --~ . . CAS P;0._
- . (pis .~. . -
14218 DYC PRODUCIS .- -. --_ -- - ...--.--- - ---_---~ -- -
tOS121NEsG
7142 _Z-til 1P0-PPp~EN!LDt011510t
Ni 000-P-4sU400142041 0"lr~~
-r
81O~ fl2~S -~ - ~--- - . .. ---- _-*----- - -. ____~ ..~~CA$.--
C0514114 0P4C
- . 10019312 t'O~AL C1t1t~tCt PMA~t4T 55*MPOG 114 cote' #01 RCi~c IOE - -- -.-- ~ - .
- 10019300 i'O*f *1 1,C1I.1ENC £1211 2H~-~OQ £0120 pL*0]PP4 £544 10 0oS3001'Z
£xcu.isCE S(P4A'1t40 P4A'POO IN C0LC-4 IOIP4UM 251 lOP - -. ~.__.__..--------- 53571.2
-- o~'ooE#t
F00193U ~ ~ C~fP~ 0.~(~OP ~ £~M lID 0053271'2
* ..1P424L L1C(ILSC( c~*'4t041 ~PO~ IN C0209 T&1!.12214 100 --
- 10021041 1~Wt&t. C(11F4C2 ~ S~0"'-0C C{1OP 4.1 A~0 £204 12005 023201.-
* ._ - - -- L'C~At. (`CEt.tChCS 1 Mt-2251 14A1~ COt-OS 4.2 0~EP #514 550004 . - ~__ .__.____-__---------
(`2~(*t~ Cti1~1.CF~ PC P°o'.1'41. S~00 IN £25040 4.2 01(9 *541 8470*21 0CS~57I'?
`C0L1(1C1. C2L~2t4~-~'PCO COLOP 2.1 tD14~ £51 853*5 ~ 002)071~?
. 10025182
* 1'05001 (tOtlfNCC 9(99*4751 A04'fl3 IN C0I.P4 5.4 St-IT *210 85044 OOS3olP-2
- -- - 10021183 2~0*L (`Ct.1(Nt~( C~t"( 7~10"P0O C2IOP.7.Z COPS I4410ESCCUT PIDNOf
Ik1)tcCO'OT 210NflP~ - CP430714?
- 10021104 L'0~F&t. 1%CELt.F1sC CPEM( 54'2550 Ct-sOP A.? POISIUM
- - - roQ7jP45 1~0PCA1 Is 11.50422 (P101 SI'~PO0 C2t.(~R 9.7 11290 .I010CSCPN1 2L0001 ._-__-_--____--.-.--*------
- L'0~!At 33005. Rt0O~3P PS~' 211012 H*jP t124l41t~P .
- - 1002-1194 L0~(Lt. P2(1(0(04CC 10 .~P41*! P45045 1.4 ISAIR CCII? LISI4L*Sli OR0b4*8k___~.__..-~-------------------
t'200L1. F'(1P4ftC( 5~t(~. 4 0&tLA-tl4~T *54 (42C4*'* (`.1 057271k.
P~'P4C5 ~9'AI-tT C2" 15 1-4*P4. Cut-3M CARs_4SH_Bt001OLJA....~
71 (050-744
- 5'OPF*I P21111204CC ROt--CS 52-901* 12470
10021197 1*00(01 PP&1P4E4(~ ~50-11 P40-Il IN 1401.1 CC(25 1410 *28.81.3802.7. ~ ~
- 010?1*1 12(1502Nd 2*105 17o-9012 COltill *5)' 5IO04C 7.15 0123270-2
- 1002*149 t'O*fAt P2-1040.5C6 ~1~''(~~ C~E~C IS H*P4 COIlS £28 810801 PA..__.........----------------- 0253C704Z
4.1 0453711'?
(`COAt- 24CFOPEP.CI 5*101 194ot't* £58
910119051 p *5.257 (241401 30 p42540 COl_00 pft37E(.$LQ#575.9
0453571
- 1,000*1 74(f (0212-CS 511(70 42451* 9*701:1. 5*_~59( ~
oCr(4'P4C F.1~8f.o241 C~41T5 14 P4010 CObS £7IRO *0800414 48 . - 4053011-4
1(721204 1~O0f £1
10-021202 12(100*1 P~F1(4ENC 91490.2*1 C4'24 55 P4*14 £0100 Lid-HI *01014(4 69 - P47-3274'
- 1.05101 F~E1P4E?-C1 001125(4221121*102041 *~c-~* o-&
£4243055 PItA 011231 71-
- 011221206 1 ~P4~4t- P'-2F2'-(570 Pf14 2412120 20591 04 -*10 C~ 311
-- - *.*. -- * - L~ootE. PojF0j114o;( oozes 110-331* 10-2 1004142 43 8053271'
lipNTfcI *374404421 718 -
144021207 15~2f Al Pr(1c0(1.-45( p1Pp#1-5~1 C40'E 05
- 1201(01 P11PoP4~ 11105 1~ot2t-t Suo#lS'110 C-JPPF~ 7.4 ..____.-_~-*-*-_ ~ .. £053270-
PP(141(PEP~~0- P4t~L I~ sAle Ct-I-OS 0101401 *U43UR~4R04 02S30-71-
100212411 1024AL
.
r1E1'1-INC( 4*415 P1~u11 PIIIZOISN P*.O'42E *,4 *- -. ._*._~_________._
1,43~41.1
10521209 1'5141 pPIFO2-EN( 01*7't51#I (4.1~t 1* 1.215 Cø13~ 202020 14104401 *o - P453074-
- - - 10(75*0-CL 5*1.125 *2-0121* LC1.0114-PL07tO5 P.3._... 1153172- -
21(110(7(1 5*149 1C.0'(2* 2(44 C0(~3 IN s*1R COLOR 9.03 1.09 201.. (~5:07I- -
10421219 150041
0-05034(2-lI ~#tt4 0,57j0* 112-90 P14)2124 911.11 4.4 - . COS37~i--
- 20571211 t'2of#l
044CF~44(2.C( 9(53111 PICNIc PPPI(CT L1P4T 2(161 lolL 002)071'-
10021212 (`02121.
-
-
544(9 1101-31 14..1~ 0412212 512.40 (4010.1. 1147* . - - - . . -**- ~ - -
* -
- 1"0-10I
* 10021213 L'C4~2t 14(110(1.11 10~I~Ct 52~;9$ IESFICT 54-17 2-1.11.1. 10 18 . 0053770
- - - - - - - - 134101 c.~(P 5125.21 4Q~f4 5pP(P SC-1T 9(160 1304 ..
- 00521214 1.12121 457 F7*F17( Pl1-14C1 o2025 01*1(21 P1*11OH *SH 10 IC 712
.
5445P 44.0401. tjt.P* 5t-1'PP P1ATtsu~ ~P4 ICTC . (153071--
(0*(A1
0~211~0~5 5(I(~T 1-04)02404 10007(1 (1t(~ OS' 10 00 . 0053'1
5~O.)( 73I'S s12414 12410C01( 921(5 1041 -. . - -- . .* (P43:70-
-* 10024278 (.53071
- 1CC'4779 100101 ~P40 04.00424 `2'2S ~t419 (15041 21011500 1004
- -. -* 20024284 19*0514 2071* 441221. 9*-.4S 501(4 sIt-v(Q 11.14(. 5011
PAGENO="0246"
- ----`- *--- -- -- CAS
TABLE 3 (continued)
01/19/18 5408 DAt P0000CIS - ,~
CONTAINISO
- ,. - ., CAR SO. 008307142 - _________________ _______
TLITROP-PH(NyLCNEOI4M4~j(
BRAWL) (LAMES
CAIS -
NU°AYER
GILLETTE Cu PEPSONAL ~5IO~ ç~)"(
P00)6449 lUST HOOP COLOR FOR INNOCENT COLOR GOLDEN BROWS 310 (COLOR SOLI -_ - ~---~- --------- 005301442
P0045450 TONI HAIR COLOR POP INN(UCLP'(T COLOR MLDflJPO GOLDEN BROWN 330 (COLOR ROLl 005307142
P00)6451 1081 5010 COLOR POP INNOCENT COLOR 721 RLOPLU)E 110 (COLOR 5011 , -- ~ - - ___ - 005307142
-P001045'( 10(41 (`(AIR COLOR FOR iNNOCENT COLOR AURU,UPA( 220 (COlOR SOIL 005307142
.FOOIH4SS TONi HAIR COLOR FOR INNOCENT COLOR AULAiRS BLONDE 180,(COLOR SOLL,,.._________ _____________
P00-44450 TOLL! HAIR COLOR POP INNOCENT COLOR HONEY 810506 (70 (COLOR 501) 005301142
-` HELENE CUJQT)$ )SDU5TPIE~ INC - -~ - - - - -- - - -
P0010355 UlTRA TONE CAERE 103-ER HONEY COIR 305 005301142
P0011377 ULTRA TOOL COERL TONER GOLD ACCERLTE0 076 -- --- ------ ------ ---- - ------------- - 005307442-
P00(135/ (ULTRA COLAPESNFNCE CAUSE COLOR SLUNR1jRST POowU~ HO 3~ 005307142
P00113&.ULTRA- TONE CAERE 100CR IVORY BLUSH 11-1,, -005307142---_
Pooiiys ULTRA COLOPESSENCE CPC-E COLOP STOPLICIT REQ 3-IC 33 005307142
P0011446 ULTRA COLORSSENCE CREPE COLOR RUOUTRIL HOlE MC 45 - ___- - ~ 005307142
ULTRA COLOPESSENCE COEME COLA? COEDER (LOW NC 44 005307142
- ((LISA CGLOTLLSSENCE CPLP4E COCOS PELT RAY HO 67 - - - ----- --------- ------ -005307(42-
P0011440 ((1102 COLOPESSEPLCE CAERE COLOR SlOb HLOSLU SC 42 005307(42', -
- -- - -- (ULT4A COLOTLSSEPCL CAERE COLOR OCEANiC P1040 HO 26,,,,,,,,,,_,,.~,,_,__,,,,,_,,
ULTRA COLOPEYSENCE CREST COLOR S0RTUGTIHE bLOND 41 27 005307142°
P001)470 ULTRA COLOTESSEPACE CAERE LOLOR SPOoR SATIN -(C 48, - - ~ --__--_ -- ---- 005307142 -
ULTRA COLORESSELCE CAERE COLOR WAlSiT AC ST 005307142 -
P001)473 ULTRA CTL~RESSEPCL CAERE COLOR INIOUSE FED MC 06 ____ __- - ~--._ -- - ------- -015307162
P00)1474 COLOOESAENCE CRERERLIR COLOR 31R P701(04 "(OAR STOWS 005307)42
- -. , -- - COLORT'SSLNCE CR151 PAIR COLOR 43 MEOIUM HEO'BROws __________- __-_ -----005307(4/_.
P0011478 COLARFSSENCE CAERE (AIR COLOR 33 1 tORT OAR-P BROwS- 005307142
COLOOESSECE C°CME HAIR COLOR 44 (00 PLC-ALE - - - - -- -------_ ---- - - -- ---.--__--_ -- -- - -- - 0053o7j~ -
COLELESSELCE CPEMC HAIR EULER 47 (`ALE (`UEO bLONDE 005307142
P0011479 COLONCASEICE CAERE HAIL COLOR 420256 AUFLURN ______ -.---__ ~-----~----_-__~ 005307142 -
COL000'SSESCE CAERE (AlA COLOR 46 11051 OL,HOLN 005307142
P0011404 COLOPESSEPOCE CR00, HAIR COLOR 31 0250,WAP:f R300PE ~ -005307242-,-
F001I453 COLOPEALEPLCE CAERE HAILL COLOR 49 (CUILLIANT RED 00531-7147
P1(01 140 COLOPESSLPLCE CAERE (21(0 CoL OR 56 IVLTENOE 3-TOO ,,-. ,,,_,____~ ~ - ---- 0053A7l4~ -
308(1 H RRCCN INC
PROIROi ARLCK 5010 COLOR NO 7 LIUPT GOLDEN BLONDE ~, , - ,,,,, - -- ~ ---- - 005307142 -
00019810 (URECO (`(AIR COlOR PLO (S LIMO RADAR - 0053-07142
- -- P0017571 (URECE HAIR COLOR NO 24 (`(OLDEN A$UAER,4LONQE,_,,,-_ -005-307042---
FP0IA0872 0)22Cc HAIR COLOR NO ?1 LIE/IT LOoN 005307142
P00-18013 BOECN ((AIR COCOA 8029 004008 SCOURS -- --_-_ 00S307(42, -
~A0(A876 H0ECR (LAIR COLOR NO 1 ULTRA LIGHT RLONOE * - 005307142
P0015019 0R0c ~AI5 COLOR N) 1611(51 *574 dROWN --------- *---- - - --005307042-
P00103-RD 00610 HAIR COLOR LEO (6.5 GINGERHROwN - 005307142
MIRIAM COIL INS P3-I'- PEACH LAOS CV - - ___________________ _______________
P0029123 lI~i LULIOHI RED 1033 - 005307(42
P0022327 hAT P000ISM 710500 (03 - - - - - - ----------- ---005317142
P0072320 (LAIR DYE REAL COPPER 1044 - 005307142
P0022379 (`(AIR EYE IICL-T 003-URN )R65 - -- - ---- --- --- -------------00S307142
P0072311 (LOlA TOP LOE001SIL RAYON (047 . 005307142
P0022337 TORCH 010s0 PEI0E - - * ____ ______________________
P00?2341 TOILER FROSTY ~EIOE - 000307(42
- - - P0022342 lOsER rPTSTY ~ - ~ ~ --------~--.~ ~~`.-~----
PAGENO="0247"
- TABLE 3 (continued) -
01/19/78 - HAIR DYE PRODUCTS . __
COo4TAINlN~,
~. .. CAR NO. - O05307R42~ ?-NlTRO-P-PHENULENEOIAHlNE.~_________________________
NITPO~P~PHENYLENEOIHUIP4E
CPOS - . BRA190TIAPES - - _~_ CAS
005 P*OD~CTS 017
--EOG14UM- 0705 CACHE COLOR RICH LTOHT AUBURN . -- - -- __-_ __- -_-.----.---- 005307142--
70014119 DON CPEM COLOR RICH LIGHT BROwN 005397142
FDO~4I2O 0705 CPEVF COlOR RICH REDDISH BOORS - . . -- - -_ 005307142
T0014I24 0705 CREPE COLOR RICH LIGHT HOsCo ILONDE u053o7147
70014125 0205 CRIME COLOR RICH LIGHT HONEY SOLO _.__~_________ __~~___..__~___C053l2142----
- 70014120 02DM CREPE COLOR RICH LIGHT ODLOEN BRORN - 005307102
700I402R 0/ON CRLMF COLOR RICH lARK DRAB BLONDE . __- _--. --_----------- - --- -. -.005307142
- 7001412) 0705 CORNS COLOR RICH CHAHPAGG RL0000E - 005307142
- (0914131 0705 CREME COLOR RICH MEDIUM ASH PL090E - . ____-------- ---- 0003o71'.2---
- 70014-13/ 0705 CALME COLOR RICH REDDISH BLONLIE 005307042
- 10004133 0/ON CPEKE COLOR RJCH REAL COPPER - ~ _~_~00530i142--
- #001413H 0205 ~EHE COLOR RICH HONEY BLONDE 005307142
- 70014139 0705 COENE COLOR RICH BPEOHT RED -- -- .~.. _~___._00S307142_-_
- 70014140 0705 CPEMF COLOR RICH PALE CHAMPAGNE BLONDE - 005307142
- - PLOVER LAROEAT001ES INC - -. ...___.~_ ___________ -- - -
#0000106 TICELED PINE NO 300 CUSTOM CREPE COLOUR 005307142
FP0IPIO8RUPOUNOY WINE NO 100 CUSTOM CREMECOLOUR_._ __..0Tl53A7142~~
-. #0016110 100)175 FLUME NO 344 CURIO-i CREME COLOUR - - 00S307L42~
- 70011594 11051 STRAWBERRY 1110510 NO 700 CUSTOM ClICHE COLOUR... ... - _._-__---------------- ~---- -- - -.--. 005307142-
#007.8001 PUSSy ELAiC in 41.6 CUSTOM CREPE COLOUR 005307142
~0o~77~ REOcEN/LAPINAL AMINO COLOR tIGHTEST GOLOEUA 800AM 40 - -- _-.__-..------- -.-----~ ---.---.- --005307142 . -
#0008271 PFDcETI,LAPINUL AMINO COLOR PEOIUM 0010(P) OPOWN 20 005307142
- 70010272. 7EDTEN/L&PINAL AMINO COLOR DARN GOLDEN BROWN IG__._ _. . 005307142---
- 7*0)8273 RCOKEH/AAPINAL AMINO COLOR LIGHTEST NATURAL ASH 88005 005307142
7OU18274 RET)SITR/LAP1NAL AMINO COLOR 110)11 NATURAL ASH BROWN ~ -- ~~~--------~- ~~-~------------ - 0*5307142- -
F.00i91»=75 PLORRR/LAOP)AL AMINO COLOR 4001DM NATURAL ASH BROWN 244 000530F1~.2
- - #0000276 PEOKEN/LARINAL AMINO COLOR MEDIUM NATURAL ASH BEOTIDE 65 - .____-._----- _~-- ------005307542
#0018277 1(~4çEP)/~ADI5R~ AMINO COLOR OARS NATURAL ASIA BLONDE SN - 005400714?
-- - - - #0018/lB RLOICET-AfL.AWINAL AMINO COLOR 0)097 NATURAl AStS.8600N1N_______________________________________ -----005307142----.
70018279 MAflOAEN1LARINRL AMINO COlOR 5411K GOLDEN 01040 SO 005307142
- - EOOIR280 REETEN/LARINEL AMINO COLOR 11091 GOLDEN HIGHS _____.____.______ 005307142
#Q010?R1 RCONEN/l.APINRL AMINO COLOR MEDIUM C.OLOEN BLONDE 60 005327142
-. REVICHONC ---------.-.----.-.--- ----------- . -
-. #0018474 REVLON COLORSILS 115)00 ASH BROWN - 005007142
._._.#00I0475 REVLON COL0050LS 400009 4SH RLONE ._~ --_______ 00S30714Z-~
- 70018476 ~E(LON CT)) OTSILK lEnTIl WARM BROWN 005307142
- . - #007.6477 PEvLOT COLURSILE MEDIUM BROWN - . ..... .--- --_- - __-. 00530714? -
10001)470 1FVLOI COACOlcIIE 11090 BROWN 007307142
70018479 ~VLOM COLOATILS 0710(5 BLONDE -- --. -- - 005307147 --
- #0010706 REVLON COIflOcILS POLE ASH BLONDE . . 005302047 -
-- - - .F09107*H - REVLON CR1084118 LI~1T GOLDEN HL000E ~ _____~-__~ _..__....005307142-..
- 7701P77.9 P~VLON CO ORSILS 0377 ASH 81050 - 005307142
* #0018710 REVLON COLONSILA SVHA44ERRY 0101101 - - __ - 005301)62 - -
70010711 REvLON CT)) DOlLS 810119 AUBURN . 005307142
- #0R19712 REVLON CR1015111) DABS BROOMS - - -... ----- 005307142
* 100)8103 0*5)05 CC-IOOSIL1) BEDIM A5H BROWN - 00530712
- - F0I1P71~ RI/ION CCLOPcIL.N MEDIUM I)ARB 40049 - - - - - _____________ -..__AAS3)7142-
* 1001071S REVLON C5.OHSILK 001 RPOMN - 0053071'?
- 70019716 PEvt0s COIDAYIIs A/FAN IA AF~ - -r
PAGENO="0248"
TLBLE 3 (ccntinu~c.i)
- 01/19/SR 1401Q DsE ~~ofl'iCic . . ~ --
Co 1*
- CR5 NO. C5530?142 ?-N1Tk9-PHfS(LENEo!oM1~ .._~ ~ ._~__._
C~1S .. NPAHO NAMES - -
HUM (P
PEVtO!',P(ALIslIC
(0050910 YOIJHGHMJP 000IJPP-t. COL0~ TOMOR OM-~ ASH RNOWPI . .. -- oos3o~1-
(0051018 YOIJ5UP4AIP tICS MI.O1U~ SMOMY 81080 00530?)-
t00?1J379 VOUTUHAIR UCI 1551 -14050 444-089 . . - - . . - - . Q0~3~7~
(00504100 Y0IJ15444)P UCI O'~~( S'Usy YQOIPI 0053011-S
- - -- F410?10(41 Y055TM4AI° HC7 LISP] f-1~ R~0S ..._. ..L.... ~ ~ - CGS3S71~'
)001RO2 yOkjU(,4019 OCT 841)00-' ASH pACIWN 005304.
F&0~'1Y']3 Y0J144~-'4A!R OCT (3544] 400814 - 0053071.
(0021494 Y]405H817 `444 00.40 tM~ 0053571.
(0021005 00~'oG4-PoTY 441 434t.C4c - - - - . -- . -. . -- -- - - - . -
70021895 Y44U05-]A30 ICY S~05I FLOODS 0053071'
- - - - 1002)597 Y0,35(4818 OCT 45050 -_._..__~_ ____. ~._.___~_.___._._~_ - __-_~___-__
10021898 S0451,#48IP tIC] 0000004 0(01(40 80O~34 ooS3o?l~s
CARSOOI 1PODIJCTS CO . -
FOO12'192 G(IDEFOOY DA54~ `H LOVELY PERMA74CNT S40SM4'OO Ill HAflOCOLUT kI A1004UR4I - -- - - -
PAGENO="0249"
TABLE 3 (continued)
01/10/78 0*10 Dv( PRO7flJCTS - -
C7P4T* 11111-IS
- - - - - - - CAS ~*O. 977061*50 -- 2_5ITPQ_P_P140MYt.ENEO1l~11M~ SuLfATE.-___------------------------------
CPIS BP*NU PIAM[5 COS
- - Rt.U'cEN LSROIIATOPIES INC ~ -
~0*11Q)5 HSt)ltlM STOIW1-EI100 5~5157f 115 1-OS CuSTO1 COLOUO 977O6111~Cl
-- 000)8702 171(0 014111 ~0 647 CUSTOI' CRIME C~L~u~ - - ___-_- __~----- _9770611157
000)5013 TIll-Ut) p10500 #0 401- CUSTOM CR101 (010178 9770617)50
-- - - - 008180)7 (1701 010.00 500 CUSTOM ~ COLOUR - --C -- - -. -- --C- -- ._ ..
100100)8 81*1-C #0 533 CUSTOM 10111 CR10110 9770611-50
PAGENO="0250"
TABLE4 ---.---. -~ ---------- --
81/19/16 HAIR 0E P000UCTS -
CONTAINIAG
- - - - -. .- -- - ~ ~ - CA5 NO. CO0119346 4.AAI40~2_N1TRQpME,AOL
BRAND UAH(5
CAS
LOIS
BE 1
* ..~. CLAIROL INC - - - - _________
10034015 MISS CLAIROL. SHAMPOO FORMULA P-T00000LD 000115346
10035160 MISS CLAIROL DAITT COLOR BOTH FLAOE,4 BLONDE - - - - - - - -- -- -- - - - ---~---__- ------___-___.. - 000119366 -
10035(58 MISS CLAIROL 1010 CC~ol MATH FLAT-P 000119340
- - 10035169 MISS CLAIROL HAIR COLOR 041(4 TOPAZ - -_ - -- - -._-_. - - -- -- 0001143.6 -
- 10035172 MISS CLAIROL HAIR COLOR (OATH 5014 MRON/I-
-. F0135173 HISS CLAIROL HAIR.COLOR (OATH C04'PLPTOSE
- 10035174 MISS CLAIROL ((AIR COLOR HATI S2APLI0 SHERRY 0001193.6
-.... Foo:5116 MISS CLAIROL HOIM COLOR A3ATH RED SIIAPOB - - ---------------------------------- --000119346 --
* 10035103 1(0 FASHION 04)14 SILvER 000119345
- F003S1~4 RED FASHION P1140 SILVER- - _--__- --__~ - -- ~ 000119366 -
- 10035165 RED E0Sl1IO'1 CHERRY SILVER 0001 17346
-- - 10034106 SILVER DROPS*~~* --~ - -- 000115366..
- FC0351V1 FIVE MI44IJTE (01041 BEOPIOE 0001193'.6
* 10035100 FIVE MINUTE CRUX AURORA - - _**_ **_ *~_ 00Sl15J.~
100)5193 NICE A140 EASY NATURAL PALL A5H RLOI4OE - . 000119346
100)5194 NICE 6140 EASY NATURAL LIGHT BEIGE HLONOE . _*~ 0001153~'.
- E003519v NICE A-ID EASY NVT~3PY1 ASH (WORN 000114145 1
F 0034213 CAERE. TQDPR 50 TOWHEAD -. 0TCl14340~~
- 10034214 CAERE TOsFA IOU SANDY EL000L 0001(93461-I
10035245 CAERE TONER 00000 LITE A - - - -- *~ - - - ** - - 0000193661
10034210 CPEOE 101410 EXTRA LITE B 000114346
10034217 CPC~E TOIlER EXTRA LITE 5ILOERY RLOUDE . - - - - - -- -- 000414346
100340(8 CAERE T0414 5110(0 SPOsE 000(19346
10035719 CAERE TONER SILVER OLD - - - - ~
10035220 CAERE TONOR POOY4RIA(O BLONDE 000(14340
- 10034221 C0EX'E TOS5R STRAW.4E000 BLONDE -- ------- - - ---- --_- -- -- - _---_ - 0001193.6
- 10035223 CRE'E TOIlER 0110(41 PLATINUM . 000119346
- 14035220 CAERE T0TAFç C000IADSE ELIDE - - 0501(93o6 --
- 10035221 CECRE 00011 SILVER OLIVE OOA1(93-5
- -- 1003527 CREXE TOIlER NOSE OLIVE ______________
10134229 CREME TOIlER (IUTT(PCUP FF105 001IIflos
10035230 CAERE TEllER 100.41 CHTFFO14 ** *~_ - 000119340
10035031 CAERE TONER ~04EY CHIFFON 000(14366
- 10035734 CAERE TONER C(IARPAGNE ICE _*~ ~ CO0I4s3~
10035239 CAERE (ONTO CHOYPO9sE SHEERLy 000110046
* 10034239 CPLAL 10059 CHAPPRUSE PARFAlI _________
- 10035?37 CRL"E 104(0 EIIARPA&.E TOAST 0001IS3'.6
- *. 10030238 CAERE 0044CR MARS PEAPL - - -- - -- -"~- - - ------------------- -000115346 --
* 1003004S LAOS CLAIROL LADY LIGHTS MOON (((bE 814 000119346
- - NATURALLY ELOSLIE NATURAL PEARL - . -- 405 - * - _. ~ ~ --000114346
10035240 COMPLETE RL000E COMPLETELY HONEY 165 000119346
LADY. CLAIXOL LADY LIGHTS XOYIE240CKL( $LONOE_.._ ________
NATURALLY ALO.DE (AlA-HAIRED RL040L 406 . 000119346
00035247 COMPLETO RLONDE COMPLETELY OLIVE - 167 - - . 000119346 -
* LADY CLAIROL LAOY LIGHTS SPUN HONEY - 816 090119346
-~ NATURALLY BLOUSE SOT-lAY BEIGE - - 407 - - - _*___ - -_ 0001193,4
10034248 LADY CLAIROL EAOY LIGHTS HA7Y MOlLY 818 000119345
KATUPALLY 01045 TRULY REIGI 408 __._._ ~ 001I1936A_
* F003S7~9 COMPLETE BLONDE COMPLFTEL0 FLAXEN 169 000119140
- LAOS CLAIROL LAOS LIG4ITSM(ILDEUA.HISPER - ~. `~RRX~ ~I00T)I(5(46 ~
PAGENO="0251"
CPIS
NLT'BER
CAS
-- - .-. - - - -- - -- ------ - - --- - - -
* CLAIR(!L INC *~ -
rooTS2o1 UR000ALEY 4104.ETE 5401406 HA7E - 409 000119346
.00035250 COMPLETE BLONDE COMPLLTELO TOWYTCOD * - 161 - .. __-_-__---.-- _~_- -- -0001193.6 -
1600 CLOIPOL SOY LIGHTS TOUCH or TAUI-T- 822 000113546
TIAIORALIY 1400400. SIFTLU 0040 410 - - ___. - _____ 006113)47
00035251 CR871001 010601 COMPIITILY ASH 0104400. 063 oRG
- LADY CLAIROL LADY LIGHTS 0129111 5260 ___.______824~ ________ ~-000I19346 --
* - NATURALLY 010401 SwEDISH CRYSTAL 411 000119346
- - - 10035252 N4100ALLY BLONDE AU1000 ASH - - .. . _----_----.- 000019346 --
- 00025253 TAATIJRALIY RLOI.Dt-EVRNING ASH - O0O1193oY~
- - 00035256 000000ILo 01050 IUS~Y FAWN - -- ---- --------- - *-- - 000119346 -
09015255 NATURALLY 0104,1* SOFTLY 610500. 000119346
0000S256 NATURALLY OLOsUL SUN TOUCH - ____~_.~ -- 000119346--
-- 00035257 NATURALLY 1107401 WILLOW T3LO'-&DE - - 000119346
00035259 NATURALLY 13L0440E 010606 GLOW .~_* -- -- ____..*.*____ -- 000119346 -
- 00035259 MOSS CLAIROL #40114 COLOR OATH SU7&IT BROWN 000119346
00035260 HISS CLAIPOL HAIR COLOR OATH MOONLIT BROWN .._*_- - _-~-_-.- ___._---__- 000119346 -
- 00035290 14155 CLAIPOL HAIR CR1041 BATH 016110 WHFAT 0001193464
00035262. HISS CLAIROL -4019 CR100 OATH 5RPI~40 HONEL...L.._.___._..~_ 0001I9340~.,
* 00035263 MISS CLAIROL lAIR COLOR MATH 0010413 MIST 0001193460.
- 10035264 NATURALLY BL0NUE OPALINE 1140AM ---- *.* *~.._-~~~-.--...-----.- -~ 00O1I9346~
10035265 NATURALLY BLONDE OPALINE I4EIOE - 000111346
-, 00035266 NATURALLY 010601 0001160. ASH - -- ~_-- ---.--*- ---**-.---.--*-- -.- __. --_---.. 0001)93.6--
00035355 NATURALLY BLONDE. SWEDISH TAFFY 000119346
- ~ 00356.9 NICE.400 EASY 64001001 LIGHT BEIGE BLONOE8103_._..________
- 00035654 NICE *00 EASY NAT~0AL PALL ASH BLOOLTE 1101 000119346
02014 00000CTS DIV - *._-*-. _...___-__-.-___*---_- __--.-----.--------------- -
* 00004010 02010 CR0.4-IF COLOR RICH LIGHT AUBURN 000119346
- -- - 0001.120 0700 CR1140 COLOR RICH REDDiSH 000014 -. - *. ..____. ..___*_____--~-----------.------ 000119346
00016126 0200 CRIME COLOR RICH L1HHT GOLDEN BROWN 000119066
* *____f0016032..OZON CARRIE COLOR RICH 60.001514 PLOIIUC._...._...
-- 10014133 0_ON C~E14E COLOR RICH HEAL COPPER - 000119361
-- 00014130 0200 CRETE COLOR RICH BRIGHT RED ...._ _._ - - ..._.___~_ ..._ *__________*- 000119346 -
- R6O.(1PW LABORATORIES INC -
- - 00012009 CHEMPAGNI BLONDE HO 1040 CUSTOM CRIME COLOUR - ~.~*~~--.--------* ---------------- *~---- ---_--000119366 - -
- 00018016 WICHITA WHEAT `40 9?6 CUSTOM CRIMP COLOUR - 000119)46
- 00018476 REvLON COLOPSTLT( MEllON WARM I~ROwN 800119346
00018710 REVLON COL085ILK STRAWBERRY BLONDE - *.... - -_*____-*- - ---- - *--- 000119346
100)071) REVLON COLORSIEK RECTUM AUBURN 000)19346
- * 00010712 REVLON COLORSILK 10006 AUBURN - * - - - - - - - - -- *-------.- - -_- -- - - ---.- 000119346 -
- RIVLGWR0ALISTIC -
- 10020007 *YOUNITHAIR NCT 64)00400. - ___ ..___~__._.~___..____._____.0001I9346 -
-- 10021088 YOt,NOHAIR OCT NATURAL MEDIUM 80046 000119)46
CARSON PRODUCTS CO - . -- ---
- FOO18~i92 GODEFROY 0917K `14 LOVELY PERMAT$EHT STIAM000IPR HAIRCOLOR KIT 600086
- * TAT3LE 4 (continued)
- - 01/19/78 HAIR Dvi PRODUCTS
CONT616INS
- - -. -- - - -- - * - - - - - COO NO. 000119346 - 4~VMIH02NITROPNEP40L
BRAPSI NOMAD
-- --. PAGE 2-------
PAGENO="0252"
246
-25-
Absorption
Numerous scientific studies indicate that the aromatic Compounds
used as dyeing agents in hair dyes can penetrate human skin. Indeed,
to the best of our knowledge, all hair dye ingredients so far tested
have entered the bloodstream of the species tested. Moreover,
Maibach at al. have demonstrated that the scalp is a preferred
cite of absorption, allowing about 4 times as much penetration as the
forearm.
In studi.es with semipermanent hair dye chemicals numerous authors
10/
have demonstrated penetration. Frenkel and Drody showed percutaneous
11/
absorption of Mc blue #1 in rats and rabbits. Maibach ~t al.
detected hair dye chemicals from two commercially distributed sgmi-
permanent dyes in the urine of humans, rats and rabbits after their
12/
hair or fur was dyed with the product. Two authors have raported
urine discoloration in women, suggesting presence of dye chemicals in
the urino, after hair dyeing with commercially availablo semi-
permanent dyes.
Similar results have been observed with permanent hair dye
ingredients. Exploratory akin penetration studies conducted for FDA
13/
by Feldmann and Maibach indicated that 4~kPD is found in the urine
of humans and monkeys after applicotion to the skin. l4~ labeled
4Mi~TD was applied to the forearm of 6 adult males for 24 hours and
urine collected for 5 days. The estimated mean total penetration
durini this five-day period was 3% of tha applied amount.
l4'
Kiase et al. applied MPD, P?D ar.d 2,5TDA to the abdom~n of
dogs. All three compounds penet~ated the skin, as determined by
blood or urine measurements taken ofter the 3 hours of application.
PAGENO="0253"
247
-26-
Oepending on the solvent in which the PPD was applied, either 1.1%
or 6.7% PPO was absorbed. Anout 2.9% 2,STDA was absorbed. If
hydrogen peroxide was added to the ?PD before application, no pene-
tration was recorded. Howaver, the measureft~ent technique used was
sensitive only to about .2% absorption. 2,5TDA was found in the
urine of dogs following £pplication of 2,STbA and hydrogen peroxide.
No 2,STDA' was found £n the blood, but the limit of the measurement
technique was also 0.2%.
NieCe and Rauschetmeasured the absorption of 2,5TDA through
human skin. The hair of 5 persons was dyed with a simplified hair
dye prapardtion contain~Og 2,5TDA, hydrogen pero*ide and the coupler
resorcinol for 40 minutes. The hair and scdlp were then thoroughly
washed. The authors found that an avetage amOunt of 3.66 mg per
persoi~ of the diacetyl derivative.of 2,5TDA was excreted in the
urine during the two days after dyeing. Based on calculations
derived from injecting a known amount of 2,5TDA intO humans, the
authors calculated that 4.6 xr~ or 0.33% of the applied 2,5TDA was
absorbed.
The penetration of 2,BTDA in rats and dogs has also been studied
16/
byHruby. Animals wete exposed to radioactively-labeled 2,5TDA
in hair dye formulations containing other primary intermedietes and
couplers. The fothulations, similar to coxrme~cially available hair
dyes, were mixed with hydrogen peroxide before application. In the
rat studies, the dye formulations were applied for 30 minutes and
than the skin was washed and dried. After 24 hours the animals
were sacrificed~ In the dog studies the formulation was applied for
3 hours and then the skin was wanhed and dried. Blood, urine and
PAGENO="0254"
248
-27-
feces were collected for 5 days. Results indicated that 0.21l%±
0.04% 2,5TDA absorbed through rat skin from a formulation containing
4.0% 2,5TDA. 5.2% ofthe radioactivity remained in the siteof
application, suggesting that absorption may continue even after
thorough washing. If so, absorption would exceed the 0.211% measured
after the 24-hour sampling period. 0.208% 2,5TOA absorbed through
rat skin from a formulation containing 3% 2,5TDA. 9.3% of the
radioactivity remained in the skin at the site of application.
Approximately 0.218% of 2,5TDA absorbed through the skin of the dogs
tested.
17/
Feldmann and Maibach have shown that labeled 2,4TDA is
absorbed in significant amounts through monkey and human akin. The
authors estimate, based on measurements taken over a 120-hour period,
that approximately 46% of the applied 2,4TDA penetrated the skin of
monkeys and approximately 2O~ penetrated the forearm of humans. In
a similar study with labeled PPD, about 12.7 ± 7% per person of the
applied PPD was found oVer. a 5-day pétiod in the urine of six human
18/
subjects. This figure was not corrected for retention in the
body.. Skin penetration of PPD is also supported by the repeated
association of PPD-containing hair dye products with the development
19/
of cutaneous reactions in humans.
All of the studies described so far have measured only the
absorption of the primary intermediate or couplers. No measurement
has been made of the absorption of the inultiringed colored products
of the hair dye process. However, studies with multiringed aromatic
PAGENO="0255"
249
-28-
compounds similar in structute to the colored products of permanent
* hair dyes strongly suggest that these products are also absorbed. For
example, the semi-permanent hair dye chemicals described earlier in
20/
this section. are multiringed aromatic compounds. Kiese et al.
report that the multiringed compound, l3androwski's base, formed while
dyeing hair with permanent hair dyes containing PPD and hydrogen
peroxide, absorbs through the skin of dogs. Similarly, there is
extensive evidence that the aromatic amine, and known human carcinogen,
23/
benzidine absorbs through the skin. Evidence also exists for the
absorption of other aromatic amine carcinogens. Based on this
kind of supportive evidence, Mies concludes that ag mt~ch as 1% of
hair dye amines (primary intermediates, couplers, and colored multi-
ringed products) are absorbed by the average person using a
22/
commercially available, permanent hair dye.
The studies descFibed above, quantifying the absorption of
primary intermediates or couplers from commercially available perma-
nent hair dyes, ~upport a general claim that anywhere from 0.2 to
0.35% of ~he amount of each chemical applied to the scalp is absorbed
through the skin when a person dyes their hair. Based on this
percentage, it is cflear that consumer exposure to hair dye chemicals
can be considerable. As an exaipplo, the average person dyeing his
or her hair once a month, using a dye with an average amount of
2,4DAA (600/mg dyeing), puts 7.2.g of 2,4DAA on their heads each year.
Using the 0.33% absorption figure for 2,STDA, one can estimate the
absorption occurring from the use ~f2,'4t~AA~~see Table 5 , page
~/ It i~'clear that several factors influence the validity of this
comparison-..th~ relative rates of absorption through the skin of
2,4 DAA and 2,S'-diatnin~toluene and the pèrcènt of each comp~ound
placed on the scalp available for absorption. While these factors
may differ for both compounds, quantitative information on each is
nor available at this time.
PAGENO="0256"
250
-29-
TABLE 5
Absorption of 2,4DAA
Amount of 2,4DAA in Product Estimated Amount of 2,~4!~
Absorbed~j~~g~
As Percent of Product Monthli Yearly
600 ]. 2 24
1200 2 4 48
3000 5 10 120
for example, where 1 per cent or 600 mg of the product is 2,4DAA,
the estimated yearly absorption is 24 mg.
Theze estimates of absorption are consistent with the data of
2~'
Ames et al.~ As mentioned, Ames concluded that "a woman under-
going one hair dyeing (with about 4g of amines) could absorb as much
as 40 mg (1%) of hair dye chemicals (precursors, products and side
products) through the scalp." Assuming that hair dyeing occurs
monthly, this is equivalent to 480mg absorbed per year. In a
formulation currently under test for carcinogenicity by the CTFA,
2,4DAA is present as 2% of the total product and approximately
25% of the unreacted amnines. Our estimate in Table 5 that 48 mg
of 2,4DAA would be absorbed from such a formulation seems reasomable
because 2,4DM comprises over 25% of the ur~reacted `amines and 48 mg
is only 10% of the total amount of amines estimated by Ames to be
absorbed. Clearly, data on the rate of formation of products and
side products and the rates of absorption of all precursors, pro-
ducts and side products must be known to quantify precisely the
absorption of 2,4DAA.
It is interesting to compare the estimated amount of 2,4DAA
absorbed with the amount of the known human aromatic amine carcinogen
PAGENO="0257"
251
-~30-
benzidine needed to cause a significant increase in cancer rates.
Such a comparison is not intended to imply that these chemicals have
the same carcinogenit potency. The validity of such an assumption is
unknown. However, such a comparison is meaningful in evaluating
human exposure to 2,4DAA.
An estimated cumulative dose of 200 mg/kg of benzidine gave 52%
tumors among a group of workers; an estimated cumulative dose of
50 mg/kg gave 22% tumors among another group. A woman dyeing her
hair with a dye containing 5% 2,4DAA would receive a cumulative
dose of approximately 50 mg/kg in only twenty years. Many people
dye their hair for that period of time.
It is clear that a consumer's exposure to 2,4DAA over a life-
time of hair dyeing can approximate levels of occupational exposure
to the known human carcinogen benzidene that have resulted in
unacceptable cancer incidences. This is clearly a cause for concern.
Moreover, this c~omparison is based solely On the absorption of one
coupler. A person using hair dyes will aleo absorb similar amounts
* of other primary intermediates and couplers, and unknown but
signifibant~ amounts of multiringed products.
24.600 0 78 . 17
PAGENO="0258"
252
-31-
Mutagenici~y~
A number of hair dye chemicals and commercially available hair
dye products cause gene or chromosome mutations in bacterial cells,
mammalian cells, or insects. Gene or point mutations are changes
in the base pair sequence of DNA. Chromosome mutations involve
changes in the number or structure of chromosomes.
The induction of mutations by hair dyes is significant to human
disease incidence for two broad reasons. First, numerous crippling
human diseases are caused by mutations, for example, mongolism.
Second, a positive result in certain tests for mutagenicity is considered
a highly reliable predictor of a chemical's cancer-causing .ability.
The Ames test for bacterial mutations and the test for morphological
transformation of mammalian cells in culture, for example, accurately
24/
identify about nine out of ten cancer-causing chemicals.The
Occupational Safety and Health Administration's cancer policy accepts
a positive result in assays for mutagenesis in bacteria, yeast,
prosophila, mammalian Somatic or germinal cells, DNA damage or repair
or in vitro neoplastic transformation of mammalian cells in lieu of
a second animal bioassay as sufficient to ic~entify a carcinogenic
25/
chemical
Gene Mutations
26/
Ames, et al. tested 169 permanent hair dyes for mutagenicity
in the bacteria Salmonella typhimuriun. The dyes, made by 8 different
companies, were bought by the author *at two local drug stores. One
hundred and fifty out of the 169 formulatiofls tested were mutagenic,
with mutagenic hair dyes found in the product line of each company
tested. The authors also tested 18 individual chemicals in
PAGENO="0259"
253
-32--
permanent hair dye formulatiorts. Nine of the 18 were intitagenic.
The mtttagenic compounds, beginning with the most strongly inutagenic,
were: 2,4DAA, 4-NOPD, 2-NPPD, 2,5t)AA, 2ASNP, MPD, OPD, 2A4NP, and 2,5TDA.
The authors also reported marked increase in the mutagenicity of
certain hair dye chemicals after mixing with hydrogen peroxide. The
mutagenicity of three para-dianiino compounds, PPD, 2,5DAA, and 2,5TDA
was dramatically increased after oxidation by hydrogen peroxide;
mutagenicity of the latter two ccmpounds irtoreased over 40-fold,
27/
Similarly, preliminary results of NCI experiments indioate that
the oxidation products of 2,4DAA, PPD and hydrogen peroxide are many
* times more mutagenic in the Ames test than 2,4DAA alone. These
results are especially significant for assessing human risk posed
by hair dye use because large amounts of these oxidation products
* are formed on.a person's head during the dyeing process.
Ames et. al also examined 25 semi-permanent hair dyes. Most of
* these were mutagenic in the Ames test..
A number of hair dyes were tested for mutagenicity in Salmonella
* by Searle, et al. These dyes were proprietary preparations and
therefore their ingredients were not~ reported by the authors. Seven
of the 11 dyes were strongly mutagenic. Of these, six did not require
microsomal activation. Thin layer chromatography on the mutaqenic
dyes indicated that 6 of the 7 dyes contained fractions o~ high
mutagenicity correspoth5ing to 2-NNPD and/or 4-NOPD. 4-NOPD Was about
3 times more potent than 2-NPPD. The identity o~ the mutagenic
agent in the one hair dye that required microsomal activation was
not precisely identified, The dye, however, was noted to contain an
azo-dye metal derivative and an amino nitrophenol.
PAGENO="0260"
254
-33.-
29/
Venitt and Searle tested numerous semi-permanent, permanent
and temporary hair dyes for mutagenicity on the Ames teèt. Neither
the names of the products nor all their ingredients were revealed.
All eight semi-permanent dyes were mutagenic. Most of the products
contained 2-NPPD and/or 4-NOPD. Similarly, all thirteen permanent
dyes were mutagenic after S-9 activation. Three hair dye ingredients,
OPD, MPD and PPD, were mutagenic after S-9 activation. Significantly,
mutagenic activity increased when hydrogen peroxide (H202) was mixed
with the individual ingredients. Six temporary hair dyes were also
investigated. All were mutagenic after 5-9 activation.
30/
In the Ames tests by Sugimurá numerous semi-permanent and
permanent hair dye ingredients were found to be mutagenic. Specifi-
cally, the following ingredients .were positive: 2NPPD, 4NOPD,
2A4NP, 2A5NP, 2,4TDA, 2,5TDA, 2,4DAA, 2,515AA, OPD, MPD and PPD. The
mutagenicity of 4NOPD and 2,SDAA were also demonstrated in Salmonella
31/ *
by Mohn and deSerres. 4NOPD and 2,4DAA are alsomu.tagenic.in
32/
yeast. -
33/
Palmer et al~Thested hair dye ingredients for mutagenicity in
mammalian cells. NPD, 2NPPD, and 4NOPD were positive. 2,4DAA gave
a questionable response and 2,SDAA was negative. However, the assay
was carried out without microsomal activation.
Chromosome Mutations
Several, studies have shown that hair dyes and their ingredients
34/
cause chromosome mutations in cultured mammalian cells. Searle et al.
PAGENO="0261"
255
-34-
found that 2NPPD causes a considerable number of chromosome and
chromatid gaps and breaks in cultures of human peripheral blood
lymphocytes. Cells incubated with 4NOPD do not show chromosome mute-
35/
tions. Xirkland and VenitEreported that Chinese hamster cells
cultured with 4NOPD and 2NPPD have a marked increase in the percentage
of metaphases containing chromosome aberrations and in the number of
aberrations per cell. Benedict indicated that 4NOPD and 2NPPD also
cause chromatid breaks in cultured hamster cells, and that 2bPPD
exposure. results in abnormal metaphases of the type related to
malignant transformation and oncogenesis. In addition, Benedict~
pepørted that 2NPPD and 4NOPD cause morphological transformation of
cultured mouse cells. The transformAtions are of the type that usually
produce sarcomas when injected ihto immuno suppressed mice.
Animal Studies
-~
B]ijleVen found that PPD, 2,4DAA, 2,4!tDA and 4NOPD induce
sex-linked recessive lethal mutations in Droso~hila melanogas~ç~.
The peak mutagenic activity occurred in metabolically active sperm
cells.
38/.
Hossack and Richardson tested hair dye ingredients for muta-
genicity using the rat micronucleus test. All of the following
chemicals were negative: PPD, 2,4DAA, 4NOPD, 2NPPD, PAP, MAP, 2A4NP
and 2,STDA. Prom the perspective of predicting chemical c5cino~--
genicity, this test has a high number of false negatives.
40/
Burnett at al. reported no dominant lethal effect in rats of
2NPPD, 4NOPD, MPD, OPD, PPD, 2,5TDA, 2,4DAA, 2,5DAA, 2A4NP, 2ASNP
and 4A2NP~ ~he relevance of these results for predicting carcinO-
genicity is marred by the high number of false negatives reported.
PAGENO="0262"
256
-35..
for carcinogenic compounds £n dominant lethal tests.
Moreover, the doses and number of animals used were too small to
assure accurate resu~Lts.
Summary
Table 6 on page 36 summarizes the positive mutagenicity data
for hair dye ingredients. Table 7 lists ingredients whose mt~ta-
genicity is increased by mixing with hydrogen peroxide.
TABLE 7
Ingredients with Increased Mutagenic Activity on Ames Test After
Mixing with Hydrogen Peroxide (H202)
2,5DAA
PPD
2,5TDA
2, 4DAA
opo
MPD
It is obvious that a large number of hair dye ingredients are muta-
genic in a variety of tests, including measures of gene and
chromosomal mutations in bacteria, yeast, Drosophila and a variety
of cultured mammalian cells. The studies described above also
indicate that a majority of marketed hair dyes, permanent, semi-
permanent and temporary, are mutagenic. In light of the correlation
between mutagenicity and carcinogenesis and the potential for human
genetic di~ease, these results must be considered alarming.
PAGENO="0263"
TABLE 6 Animal
Pounds Carcino-
Tests for Mutagenicity used/yr gem
Mammalian Mammalian
Mouse Chromosome Morphological
~gredients Ames Yeast Lymphoma Mutations Transformation Orosophila
2,4DAA Ames Moyer Blijleven 25,000 yes
Sugimura
4~0PD Vennitt & Moyer Palmer Kirkland ~Benedict Blijieven 7,500
Searle Benedict
Móhn, Ames
Sugimura
Searle
2,5DAA
2,5DAA Ames
Sugilnura
Mohn. 7
2A5NP Ames
Sugimura 500 7 ~
cr
MPD Ames Palmer 500 7
Vennitt &
Searle
Sugimura
2A4NP Ames 1,000 ?
2,5TDA Ames
Sugimura 22,000 no
PPD+H202 Ames
2NPPD Sugimura Palmer Searle. Benedict 24,000 yes
Searle, Ames
Venitt &
Searle
OPD Venitt & Searle
Sugimura
PPD Venitt & Searle BlijleVefl 75,000
Sugirnura
PAGENO="0264"
258
-37-
Animal Carcinogeni~~
The carcinogenicity of hair dye formulations and individual
hair dye chemicals has been evaluated in animals through inges-
tion and skin painting studies. These studies, reviewed below,
indicate clearly that exposure to hair dyes and hair dye ingre-
dients either through ingestion or skin painting, results i~n an
increased incidence of tumors. Specifically, NCI data indicates
that 2,4DAA, 4A2NP, direct black 38, direct blue 6, 2NPPD and
2,4TDA are carcinogenic iii rodents.
Feeding Studies
42/
A recent report from the NCI summarizing the results of
a study in which 2,4DAA was fed to mice and rats concluded,
"Under the conditions of this bioassay, technica3~.qrade
2,4 diaminoanisole sulfate was carcinogenic to both sexes o~
both species."
The NCI ~periment was conducted according to Standard
carctnogenesrs bioassay protocols. Rats (Fisher P344) of both
sexes were fed ad libitum diets containing either 1200 (low
dose), 5000 (high dose) or 0 (control groups) parts per million
(ppm) of 2,4 DAA. There were 50 rats in each group (except for
the male rat high dose control group, which had 49). Similarly,
three groups, each containing 50 male and 50 female mice (A.R.
Schmidt B6C3P1) were placed on ad libitum diets containing
1200 (low dose), 2400 (high dose) or 0 (control group) ppm 2,4 DM.
After approximately two years, the animals were sacrificed and
pathologically examined for cancer. Results of these examinations
PAGENO="0265"
Adenocarcinoma, NOS; 4%
Papillary Adenocarcinoma;~ (2/43)
Follicular-Cell Carcinoma;
or Papillary Cystadeno-
carcinoma, tCS
P~denocarcinoma, NOB; 4%
Papillary Adenocarcinoma;. (2/4B)
Pollicular-Cell Menoma;
Pollicülar-Ceil Carcinoma;
Papillary Cystadcnoma UO~;
or Papillary Cystadenocarcinoma,
NOB
In the high dose group the number of rat8 having either one of three
groups of thyroid. tumors or adenocarcinoma, NOB was significantly
greater than the correapondizr~ control gtoup.
~/ The figure indicates the ratio of twnór bearing animals found
to the total number of animals examined.
~J The p values listed were determined by the Fisher exact test.
259
38-
are pre~sented in Tables 8 - 17.
Male rats showed a statistically significant increase in a
wide spectrum of thyroid tumors (Table 8).
*TABLE8
Tncidence of Thyroid Tumors in Male P~a~
~pe of Tumor Incidence of Tumor
Low Dose High Dose ~w High
Control Control Dose Dose
Adenocarcinonta, NOB 4% 0% 2% 29%
(2/45)tJ. (0/48) . (3/47) (14/49)
P 0.05-
C--Cell Adunoma or.
Carcinoma . 2%
(1/45)
2% 9% 20%
(1/48) (4/47) (11/49)
p~0.O5
0% 4% 35%
(0/48) (2/47) (17/49)
p(0 .05
0% 4% 40%
(0/48) (2/47) (20/49)
p<0.O5
PAGENO="0266"
260
* -39-
A statistically significant increase of epithelial tumors of
the integumentary system was aino observed among male rats. These
tumors were fow}d in the skin (Table ~), the preputial gland
(Tablo l~, and the ear canal'and zymbal gland (Table 11)'.
TABLE 9*
Incidence of Skin Tumor in Male_~ts
Low Dose
Control
0%
(0/4 6)
Incidence of Tunio~
ifigh Dose Low High
Control Dose Dose
0% 0% 10%
(0/48) (0/48) (5/49)
p<0.O5
Type of Tumor
Squamous-Cell Carcinoma
Basal-Cell Carcinoma
Sabaceous Menocarcinoma
Sebaceous Adenoma
Fibrosis.
Fibrosarcoma
Squamous-Cell Carcinoma,
Baa al-Cell Carcinoma,
or Sebaceous Adenocarcinoma
All Tumors
0%
(0/46) (0/48)
0% * 0%
(0/46) * (0/48)
0% 0%
(0/46) (0/48)
0%
(0/46) (0/48)
0% 0%
(0/46) (0/48)
0% 0%
(0/46) (0/48)
0% 0%
(0/46) (0/48)
2%
4%
(1/48)
(2/49)
2%
6%
(1/40)
(3/49)
0%
2%
(0/48)
(1/49)
8%
2%
(3/48)
(1/49)
*
2%
(1/48)
4%
(2/48)
2%
(1/49)
18%
(9/49)
,
.
p.<0.05
12%
(6/48)
24%
(12/49)
p7
PAGENO="0345"
3~9
Dr. FINE. These are some examples of known human exposures
to N-nitrosamine compounds. This is an attempt at this. Someofle is
inhaling air and there is a certain N~nitrosamine level at a certain
factory. They may be eating a bacon sandwicWor they may be working
with pesticides or working with cosmetics. How do you try to relate
the exposure?
What we have done is to assume a normal lifestyle with a person
working in a city who may inhale 10 cubic meters of air a day, and a
person using cosmetics may apply 1 gram of cosmetics to their face
a day.
From this you can begin to correlate at least what the different
exposures are.
bgesting of'foods at the very most could be about 1 microgram per
day of nitrosodiethanolamine or N-nitrosodiethanolamine, exposure
to cutting'fluids, may be anything from 25 to 250 micrograms per day
by inhalation and up to 25,000 by contact with the skin.
Cosmetics, with a single application of the ones we have looked at,
could be anything between 50 and 100 micrograms per day.
* Smoking a pack of cigarettes of 20 cigarettes a day would. account
for about 3 or 4 micrograms per day. So, one can `begin to correlate
`these numbers.
What this still does not take into account is two aspects. No. 1,
the different exposure :routes Some of these are by inhalation or
skin cofrtact or ingestion.
Secondly, the various relative toxicity of a' compound should be
taken into account. Sonie are relatively potent carcinogens and some
are moderate. At the present time I do not thiñk' `any scientist can
make a better correlation than that. We dO not know' how to extrapo~
late, beyond that kind of ~uimbers which you can calculate and have
confidence in. The restis guess.
Ms. LEAL. Last week there were questions raised by CTFA between
drawing conclusions `or drawing a link between eancer~causing agents
in animala and their applicability to humans. Can you cothment on
that?. . `
Dr FINE As a resoai ch chemist, I think that is out of my line of
"expertise. I would be getting into areas that I know very little about.
Ms. L~AL. Do you know of any' scientific knowledge that would'
shed some light on~that? ` ,` `
Dr. FINE. Let me quote some things about N ~nitrosamines which
are known. `. **
There are about 130 N-nitrosammes which baire been-or corn-
pouhds, to be `more s'cientificalW' correct, which have ~been tested in
animal experiments. Of these, aboutfr 100, or 70 percent approximately,
are, or havO~ been shown to be, carcinogenic in animal experiments.
The animals which have been studied., of which there have been
18 different sp6ciesT, include the rat, mouse, hamster, Chinese hamster,
guinea pig, rabbit, dog, trout, parakeet, and monkey If it is carcino~
genie in one species, it is carcinogenic in the other species.
In the case of the N-nitrosamines, the sites of the tumors vary,
sometimes depending on how it was obtained, that is, whether it was
by mgestion oi~ inhalation) and also the chemical structure of the
nitroso ~cornpounds. Tumors that -have been `produced' can' be in the
kidney, larynx, or lung, or ~brain, deponding `on' the ~trueture.'
PAGENO="0346"
340
This body of evidence is in the literature about the nitroso com-
pounds with animal experiments.
There have been studies at very low doses going down to feeding an
animal at doses as low as a part per million, in the case of three
N-nitrosamines.
In the case of N~nitrosodiethylamine, a study in Germany,
showed that one part per million in the diet of 100 animals was statis-
tically significant and gave tumors above the background. That is
abQut the lowest dose that has been looked at with N-nitrosamines.
As for human studies, there are no studies that I have seen-posi-
tive or negative-on looking to see if humans are, that is, if there is
any epidemiological data related to N-nitrosamines.
The reason there are not any studies is that until 3 years ago
N-nitrosamines were not known to be a major problem with man. They
were known to be potent animal carcinogens and to be present in foods
at low levels. But a human population had not been identified to
which they had been exposed, so that an epidemiologist could go out
and study it.
At the present time there are now three or four such populations. You
have rocket fuel workers in Baltimore and certain pesticide agricul-
tural workers and people who use cosmetics and machinists who
use cutting fluids.
I know of several ongoing epidemiological studies which are be-
ginning to see if there is a correlation, but so far that correlation has
not been made. People are just beginning to try.
To say that there is no correlation has to be qualified with the fact
that no one has looked at it.
Ms. LEAL. Thank you, Dr. Fine, Thank you, Mr. Chairman.
Mr, MAGUIRE. You talked about shelitime. Have you attempted
to define in any way the relationship between the formation of
N-nitrosamines in products and periods of time on the shelf or after
the cosmetic is actually placed in the container?
Dr. FINE. We have just begun to do those studies now in our
laboratory. It was only a couple of months ago that we found that
the O~nitro compounds, on particular one in cosmetics called bronopol,
could act as a nitrosating agent. In fact, it was more efficient at the
neutral condition in a cosmetic than sodium nitrate would have been.
It created more N-nitrosamines than sodium nitrate would have.
With that finding, we now have the studies underway. We do not
yet have any data on that.
I would like to comment here on what that leads into, Mr. ChaiF-
man. There has been a lot of discussion this morning and last Thurs-
day, which I heard, on testing ingredients.
In one case in the original study we looked at two ladies' makeups,
the same color, the same shade, and by the same manufacturer.
One was water based and one was some other base. In one we found
the highest level that we reported which was 50,000 parts per billion.
In the other we found nothing.
Mr. MAGUIRE. Which was which?
Dr. FINE. I do not recall the name. It is in the data.
Here we have a situation where apparently many of the ingredients
were identical. One or two of them may have been changed, or the
concentratlon changed, I do not know what the change was.
PAGENO="0347"
341
But that~ingredient which was o~hanged made all th~ differenèe in
forming the N-nitrosamines and in not forming them. So, if you are
testing ingredients only you have to be very careful that the ingre-
dients are inert and are not reacting with time with the products.
Otherwise you can test a lot of ingredients. and certify them safe under
any kind of test that you can think of and then find that there still
is a hazard in the final product.~
Mr. MAOUIRE. Apparently there also are combinations of ingre-
dients which do not result in hazardous findings~; is that right?
Dr. Fii~. Oertainly~
From the chemistry one can develop classes of compounds, which
when mixed with each other are quite innocuous, or other products
that they may form with time which are quite innocuone
Mr. MAGUIRE. Does this imply that there are now in existence
safe substitutes that would preclude our having this difficulty with
certain cosmetics containing N-nitrosamines?
Dr. FINE. I would have to answer "Yes" for the following two
reasons. In some cosmetics we found very high levels of N-nitros-
arnines and in others we found very low levels. If we know what the
ingredients were in the low levels, those products. are obviously,
comp~redto the high levels, relatively safe.
It is, therefore, possible to manufacturer or make cosmetics which
do not contain Lnitrosamines.
We have now found that certain bacteriacides can form the N~nitros-
amine when mixed with the amine in the cosmetic. However, there
seem to be cosmetics on the market which contain other bacteriacides
or other ways of preventing bacteria growing in the cosmetic~ with
time.
So, it would seem that it is a very soluble problem.
Something similar arose with pesticides at these hearings sometime
back. Some companies had very high levels of dimethylnitrosamine
in their pesticide products. The problem was they were marketing
their products in cans which had been treated with sodium nitrite.
They took the sodium nitrite out of their cans anxi their problem
almost went away.
I think in the cosmetic area, paying attention to what the in~redi-
ents are and how they react, will probably solve the problem. Many
companies already have that solution.
Mr MAGUIRE Are these chemical reactons which result in N-nitros-
amines a function simply of the chemical componen'ts in the mixture,
or are they also variable in relation to changes in temperature or
agitation or any other factors?
Dr. FINE. Mainly the constituents. A temperatureii~ almost any
chemical reaction would tend to increase the rate The higher the
the temperature, the more rapid the rate of chemical reaction
Similarly is the agitation The more rapidly you agitate, the more
you mix things, and the more rapidly it will go But-
Mr MAGUIRE But you feel the big~ disparities you have found in
essentially similar products are the result of the chemical constituents
rather than these other factors; is that right?~
Dr. FINE. Thatis correct. ~-
Also, we feel we have the explanation in that we now have found
that some of the ingredients that cosmetics contain both the precursors
I
PAGENO="0348"
342
which form the N-nitrosamines. Two are needed and they are both
in the cosmetics.
Mr. MAGUIRE. The C-nitro compond that you are talking about,
is that a newly found compound which nobody knew about or nobody
knew that it had nitrosating qualities?
Dr. FINE. It was a known compound and widely used. There are
other very widely known compounds which have very similar chemical
structures. Although we have not tested them specifically, we would
expect them to form N~nitrosamines. Some of these are used as dyes
in cosmetics and some of them are used as bacteriacides in cosmetics
and some of them are used as perfumes. Many perfumes are C-nitro
compounds.
This does not only apply to cosmetics. Many pesticides are 0-nitro
compounds. We believe the same chemistry would help explain the
problem in cosmetics.
Mr. MAGUIRE. Have you received any support from NSF or
anybody else to continue this kind of work? What is the status of
your research now with respect to examining some to these additional
questions?
Dr. FINE. Our funding from the National Science Foundation is to
look at the generic problem of N-nitrosamines in the evnironment. We
have looked at chemistry, pesticides, and cosmetics, which are just
a few examples of the chemistry.
The way the program was set up when we got our support from
NSF, we could not get into too much depth with anyone, because
these aspects fell under the control of different agencies in this case,
the Food and Drug Administration.
So, and we do not have continue support of work on cosmetics.
Work that we have on-going is that we are planning to do some
absorption studies. We are hoping that the FDA may support that
in the future.
Mr. MAGUIRE. With respect to cosmetics?
Dr. FINE. Yes. That is not being supported by the NSF. That
is our own support.
As far as the chemistry is concerned, the mechanisms of how N-
nitrosamines are formed, again, we are hoping we can get support to
continue our work.
Mr. MAGUIRE. Are there any other categories that you are planning
to work on now with respect to a preliminary assessment of the N-
nitrosamine question? You mentioned pesticides in cutting oils, and
now cosmetics. Are there other categories?
Dr. FINE. The categories we are looking at are chemicals of com-
merce: industrial chemicals, pharmaceutical drugs, and things like
shoe polishes and floor waxes-
Mr. MAGUIRE. You are going to do that?
Dr. FINE. Some of them actually are in progress.
Mr. MAGUIRE. I see.
You indicated that the information about N-nitrosamines in cos-
metics had been transmitted some time ago to the FDA.
Dr. FINE. That is correct.
Mr. MAGUIRE. Have you received from them directly, or do you
have, any indirect information as to what, if anything, they have done
on either matter?.
PAGENO="0349"
343
Dr. Fi~. We have had several meetings with FDA where in one
cas e they came to see our labs. .1 havebeen down to see FDA scientists
on several occasions since then.
We discussed with them our latest findings on the mechanism of
w hat may be happening. in cosmetics about 5 or 6 weeks ago. We have
s ubmitted to FDA research proposals for continuing this work. We
d o notknow~ yet what the outcome of that will be.
Mr MAGmEE But they have not, to your knowledge, taken any
action with respect to the cosmetics in questior~? I am talking about
as far as their availability to the public is concerned
Dr FINE My understanding, or what I have been told, is that
they do not have the jurisdiction to restrict the sale of cosmetics
Mr MAGUIRE Do you know whether they have notified the
manufacturers, or hare you notified the ma~ufácturers in any formal
way as. to the results?
Dr. FINE. We notified, when the results were released initially in
March of last year, the manufacturers by telegram under the signature
of the National Science Foundation, notifying each manufacturer of
the findings in the~particular product.
Mr. MAGUTRE. Dr. Fine, we want to thank you very much.' `We
appreciate your testimony.
We `would like to add a person to the witness list today.
We would like to call Judy Wairath of the Yale University School
of Medicine.
Please conic ftrward to be sworn in.
Do you promise to tell the truth, the whole 4ruth, and nothing but
the truth; so help you God?
[Witness answered "I do."]
Mr. MAGU.IRE. Thank you,~Dr. Wairath for' agreeing to testify
today. `
Mr. Segal?
Mr. SZaLUA. First I would like to request that a letter that was
received by Chairman ~Tohn Moss today be inserted Into the record
at this point. It is a letter from a Dr. Aivan R. Feinstein of Yale
University, School of Medicine, commenting upon the report that
Dr Walrath was the senior editor on
It is in relation to the point ~a~scd earlier this morning by Dr
Corbett on whether or not the subcommittee has had an opportunity
to evaluate the two studies grought forth by the industry at their
prior testimony last week. ` ~ .
~One of' the' two was the study done by `Dr. Waltath and Dr. J.
Wister Meigs
You will note in the letter that l~r. Fèinstein is the same individual
who found serious flaws, gross flaws in the two NIOSH studies, and
he ends up. s~~ing very complimentary things about the methodology
usediti the Walrath-Meigs.study.
Mr~ MAGUIRE. Without objection, that letter will be placed in the
record at this point:
[The letter referred to follows:]
PAGENO="0350"
cr~. q. o
I -` ~ SCHOOL OF b{EDICINE
333 cedar Street
Robert lVood Jo/news
Clinical Scholar Program
ALVAN ~t. FEINSTEIN, M.D.,
Program Director
(203) 436-8 787
On January 25, 1978, I was telephoned by Elliot Segal, of your staff,
requesting me to send you a critical review, of studies of hairdressers and cos-
metologists performed by Dr. E. Cuyler Hammond and by Dr. J. Wister Meigs. Although
Mr. Segal said he would send me copies of both studies, I have not yet received the
Hammond report. A copy of the Meigs study, of which the principal investigator was
Judy Walrath, was sent to me (apparently at Segal's request) by Dr. Nalgs. My com-
meOta here are therefore confined to the Walreth-Meigs study, "Cancer Incidence Among
Cosmetologists", which is currently in the form of a dissertation, dated December,
1977, submitted by Walrath for the Ph.D. degree from Yale University.
The study is a longitudinal investigation of a cohort of 12~O7 Connecticut
cosmetologists who began hairdressing school before December 31, 1965; and of a
matched cohort of 11,463 Connecticut schoolteachers. Both cohorts were assembled
"retrospectively!': the cosmetology group, from license registration data available
since 1938 at the Connecticut State Health Department; and the schoolteachers, from
data at the Connecticut State Department of Education Certification. The subseqtient
occurrence of cancer i~ both groups was determined by linkage ~- via names, birth
years, and other pertinent information -- with data contained in the Connecticut Tumo
RegiStry. The linkage activities were performed "blindly", withOut kn9wledge of each
person's occupation.
The total subsequent occurrence of cancer, as well as the occurrence of cancer
in specific Sites, was noted for the cosmetologists and compared against the analo-
gous occurrence rates, in a matched, pairs analysis, for the schoolteachers; and, in
cohort analysis, *for the corresponding general population of Connecticut. The
inferential and analytic statistical procedures used in both the matched pair and
cohort analyses appear to be impeccable, with appropriate usage of Beers interpolatio
McNemar chi-square tests, Fisher exact tests, and several methods for computing stan-
dardibed incidence ratios.
In the cohort analysis, the investigators found that the cosmetologists had a
substantially ~ rate of cancer, in total ar~d for almost every specific site, than
woul4 be expected froa the corresponding rates of the general Connecticut population.
Thi~distinction is attributable to the bits of the "healthy worker effect" that tends
to make any .occupatSonal group healthier ttan the general population. In the matched
pair analyses, the schoolteachers had a higher rate for total cancer than the cos-
metologists. For individual sites of cancer, the rates showed statistically significa
differences in favor of the cosmetologists for cancers of the breast a~0~eproductive
system; and in favor of the schoolteachers for leukemia. In view of the,/1ifferent can
sites fpr which comparisons were made, occasional differences in favor of either
occupational' group can be expected toocçurby chance.
344
Yale University' New Havece, Co,z,jecticut 06510
January 30, 1978
John E. Moss
Chairman, Subcommittee on Oversight and
Investigations of the Committee on
£jtterstate and Foreign Commerce
House of Representatives
Washington, D.C. 20515
Dear Mr. Moss:
PAGENO="0351"
345
John E. 1465s January 30, 1978'
The results indicate that the tOtal risk of cancer for cosmetologists is
certainly no higher than for the general population, Snd is slightly (but not
significantly) lover than for a matched group of schoolteachers. ~Yith respect to
individual cancer sites, the results found in this cohort study contradict the
results of previous.case..control studies suggesting that cosnietologists have elevated
rates of cancers in the breast, lung, bladder, ovary, and uterus.
You have Seen my letter to Conner ~ay, dated January 20, 1978, containing a re-
view of~,two stn4ies sponsored by NIOSfl and~performed by, Decoufle ~t al. and by I~erinedy
et al. Unlike those two previous studies, the Walrath4leigs investigation was perfora
with careful attention t6 scientific `detailg, anSlyzed with eXcellent metho4s, ,and die
cussed with admirab),e scientific caution, The authors have t1~oughtful1y constdered
all of the difficulties assodiated ~qith any epidemiologic research of this type and
have pointed out the problems involved in de4ing with the basic data as well as the
issues in linkage.
The questions being asked about `the risk of cancer, from hair dyes cannot be
approached wit~i experimental research in humans and would not be answerable for decade
if investigated as a prospectiv~ cohort study. The best way to try to answer the
question now is with a large "tet~ospective" cohort study, which is precisely what
Walrath and Meigs have accomplished. A8 good scientists, they have cited the potentia
biases that are inherent in such a study, but they also indicate the absence of evidenc
to suggest that the potentia'l biaaea actually occurred. Purthermore, every one of the
potential problems discussed by Wairath and Meigs is abundantly present in the previou
`two studies, although not discussed by the othan ~thers. If not an optimal compariso
group for the cosmetologists, the teachers investigated by Wairath-Meigs are obviously
as comparable a control group as the non-specific "clerks" used by Decoufle et al. and
are ob~2Lously better than the lack of any specified control group iz~ the Keonedystudy
In the ~alrath-Meigs~ study,. futthermote, the licensure info,rination provides objective
co~nfirmation of dccupational data that were obtained `subjechvely and neither checked
nor verified' in the other two studies. Walrdth and Meigs ~l~o prbvide data for risks
accordingto duration of exposure~'an important scientific feature that is wholly
absent from the other two reports. Finally, and most cogently, the SJalrath-Meigs in-
vestigation is a population-based cohort study with a specific hypothesis. It is not
the' type of data-d~edgittg activity -- using populations of unktiówri origins ahd biases
and s~a~ing no advapce hypothes~s -- that vas performed in the other two studies.
In his telephone convetsation with mS, Elliot Segal S'~id someone had~ suggest~ that
the Walrath-M~i~s study had ~Ow `quality and cdttained the samesort of defects present
in the tvo NIOSH-aponsored tepQrts. Since the Walrath4teigs investigati9n is of ex-
cellent quality, and is so~óbviously Superior to the other two studies, this suggestior
could come only' from someone who lacks familiarity with Standards for scientific
epidemiologic research.
I understand that you are eager to have this review as soon as possible. I am
therefore sending it now. When the Rammond document arrives, I shall comment on it
separately.
Sitlcerely' youñ, `
Alvan R, Feinatein, M.D.
PrOfesse~ of Medicine
and Epidemiology
ARF :mbn
PAGENO="0352"
346
Mr. SEGAL. I would first like to ask Dr. Wairath if she could identify
for the record her training in the field of epidemiology.
TESTIMONY OP IUDY WALRATH, PH.. D., SCHOOL OP MEDICINE,
YALE UNIVERSITY
Dr. WALRATH. I received my Ph. D. in epidemiology and public
health from Yale University.
Mr. SEGAL. Dr. Wairath, among the findings that were listed in
your i~eport was there a significant increase statistically of acute leu..
kemia among cosmetologists as compared with the control group.
Co~ild you comment on that?
Dr. WALRATH. Yes. When compared, the control group with
schoolteachers had no cases, but in the cosmetologists there were
seven acute leukemia cases.
This result was statistically significant, but due to the small num-
bers, I believe that further research should be done to confirm this.
I do not believe that should be overlooked, however,
Mr. SEGAL. The industry, in its testimony, indicated that your
study was one of two that demonstrated no direct link between cancer
and hair dyes.
Based on your study, would you come to the same conclusion?
Dr. WALRATH. `No. One cannot draw a positive conclusion from
negati~ve findings, which essentially is what we had overall in the study.
I was testing to see if there was any difference in the cancer incidence
between the schoolteachers and the cosmetologists. This hypothesis
cannot be rejected on the basis of statistical evidence, but neither can
it be accepted with a lack of this information.
Mr. SEGAL. Would you conclude from your findings and your con-
clusions that more work needs to be done and that the safety of hair
dyes is something that remains, at least in question?
Dr. WALRATiI. Yes. I believe that more research should be done.
Mr. `SEGAL. I have no further questions, Mr. Chairman.''
`Mr.. MAGUIRE. Dr. Wairath, are there any additional comments
that you would like to make on this subject?
Dr. WALRATH. I do not believe so, no.
Mr. MAGUIRE. Mr. Wunder?
Mr. WUNDER. Thank you, Mr. Chairman.
Hav~e you seen Dr. Feinstein's letter?
Dr. WALRATH. Yes.
Mr. WUNDER. If you look on page 2 in the first paragraph, he says:
The results indicate that the total risk of cancer for cosmetologists is certainly
no higher than for the general population, and is slightly (but not significantly)
lower than for a matched group of schoolteachers.
Are those the results? Is that accurate?
Dr. WALRAPH. Yes, it is. Overall cancer sites combined, there was
no difference between the cosmetologists and the schoolteachers, and
overall, when compared with the Connecticut population there was
no difference.
Mr. WUNDER. Explain to me the statement you made about the
positive results from negative findings What exactly does that mean?
Dr. WALRATH. I am saying that overall there is no indication that
there i& a risk of cancer among cosmetologists, but I am saying that
PAGENO="0353"
347
this lack if information to prove this does not indicate safety or no
risk.
Mr. WONDER. You cannot prove safety on this basis; is that right?
Dr. WALRATH. Yes.
Mr. WUNDER. Because the schoolteachers and the cosmetologists
came out lower, that is, the cosmetologists came out lower than the
schoolteachers and that, in of itself, does not prove safety; is that
what you are saying?
Dr. WALRATH, That is correct.
Mr. WUNDER. What about leukemia? Is that consistent with other
findings, other epidemiological studies in this area? Or is that some-
thing new that you came up with?
Dr. WALRATH. I think that has not been found in any other studies
on cosmetologists.
Mr. WUNDER. To what do you attribute that?
Dr. WALRATH. I am not able to say5.
Mr. WUNDER. I see,
Let me ask you this. In your study, and I notice in the letter it says
that your group was from licensed registration from .the Connecticut
State Health Department.
Dr. WALRATH. Yes.
Mr. WUNDER. So this group of cosmetologists wquld not include
shampooers and electrologists and manicurists and that sort; would it?
Dr. WALRATH. The group included 77 manicurists, I believe. The
rest were, all licensed hairdressers who were all qualified to do all
duties of hairdressing; shampooing, hair dying and haircutting `and
so on.
Mr. WUNDER. There were 77 manicurists?
Dr. `WALRATH. Yes.
Mr. WUNDER. Was there anything-what about the manicurists
versus the cosmetologists versus the schoolteachers? Can you break
those out?
Dr. WALRATH. I am sorry. I do not understand.
Mr. WUNDER. You had 77 out of the 12,000 which were manicurists?
Dr. WALRATH. Yes.
Mr. WUNDER. Did they have any higher degree of cancer in. any
sites than the cosmetologists or the schoolteachers?
Dr. WALRATH. They did not. S
Mr. WUNDEE. Were they lower?'
Dr. WALEATH. I believe there wasonly one case among the 77. but
the numbers were too small to draw any conc1usi~r~'
Mr. WUNDER. Thank you.
Thank you, Mr. Chairman. `
Mr. MAGUIRE. Thank you, Dr. Walrath.
The subcommittee will stand adjourned until tomorrow at 10 a.m.,
`in this same room.
[Whereupon, at 2:20 p.m., the subcommittee adjourned to recon-
* vene at 10 a.m., Friday, February 3, 1D78, in room 2322 RHOB.]
24-600 0 - `78 - 23
PAGENO="0354"
PAGENO="0355"
CANCI~R-CAUSING CHEMICALS
Safety of Cosmetics and Haii~ Dyes
P1~TDAZ FEBBV~AR~ 3, 1978
HOVSE or REPRESENTATIVES,
SURC0MMITrEE ON OVERSIGIIT AND INVESTIGATIONS,
COMMITTEE ON INTERSTATE AND FO1~EIGN COMMERCE,
Wa$hington, D.C.
The subcommittee met, pursuant to notice, at 10 a.m. in room
2322, Rayburn House Office Building, Hon. Andrew Maguire presidmg
[Hon. John E. Moss, chairman].
Mr. MAGIYIRE. The subcommittee will come to order.
Today, we conclude this series of hearings on the war on cancer
Over the past 2 weeks we have heard testimony from scientists and
industry officials on the topic of whether hair dyes and other cosmetic
products are safe More specificially, we have explored the issue of
whether ingredients in cosmetic and hair-dye products pose an in-
creased risk of cancer to users.
The evidence collected to date suggests that we must. 1oo1~ more
carefully at not only the safety of these products but the adequacy
of the statutory authority granted to the Food and Drug Administra-
tion-FDA-in this area.
I believe that testimony before this subcommittee strongly suggests
that the cosm~ti~ section of the Foo~l, Drug, and Cosmetic Act be
scrutinized for adequacy.
Proper regulation of the safety of cosmetic products is essential
Dr Robett Scheuplem of FDA estima,tes that the average American
places 10 to 40 pounds of soa~ps, toiletries, and: cosmetics qn his or
her skin annually~ Scientific studies indicate that some ingredients
penetrate the skin and reach the bloodstream.
Research, however, has not yet demonstrated what happens when
these substances enter the blood stream Are some of them retained
in body tissues? Do they metabolize into more dangerous substances?
These are questions which remain unanswered Nevertheless,
information presented to this subcommittee suggests that numerous
carcinogens, mutagens, and other toxins are in cosmetic products
I believe we must be concerned about not only the acute effects of
these chemicals but also the chronic effects,
One important question which must be answered is Are we sub-
jecting the public to an increased and unreasonable risk of cancer or
other adverse health effects through the use of these products? In
effect, are we needlessly gambling with the public health?
(349)
PAGENO="0356"
350
The cosmetic industry has stated that cosmetic and hair-dye prod-
ucts are safe. Unfortunately, the evidence presented thus far leads
me to question this conclusion.
The cosmetic industry has stated that few consumers have adverse
reactions to cosmetic products. Information provided to the subcom-
mittee indicates, however, that cosmetics may "injure 60,000 per-
sons-mostly women-annually so seriously as to restrict activity for
1 day or require medical attention."
The testimony presented to the subcommittee raises serious ques-
tions about the adequacy of industry's testing of cosmetics. Further-
more, the record seems to indicate that FDA does not have adequate
authority to protect the public from the potential hazards presented
by these products.
After a careful review of all the information before me, I believe
one conclusion must be made-the coal-tar hair-dye exemption must
be removed. There is no logical reason why coal-tar hair-dye products
should be given special treatment under the law, especially in light
of increasing evidence that these products contain carcinogenic
ingredients.
I wOuld like to announce today that I, along with Chairman Moss
and several of my colleagues, will jointly sponsor legislation to remove
the hair-dye exmption from section 601 of the Food, Drug, and Cos-
metic Act.
Today, I hope we will obtain answers to some of the questions
raised over the last 2 weeks. I welcome CommissionGr Donald Kennedy
of the Food and Drug Administration and Mr. Gregory J. Ahart of
the General Accounting Office.
I hope, gentlemen, you can assist us in determining whether further
congressional action is needed to protect the public from potentially
harmful ingredients in hair dyes and other cosmetic products.
Mr. Walgren, do you have an opening statement?
Mr.. WALOREN. I would like to reinforce at the outset of the hear-
ings the seriousness with which the committee considers the findings.
We conclude a set of hearings that have revealed serious inadequacies
in the protection of the American public from potentially harmful
ingredients in cosmetics, cosmetics that are sold by the most tempting
advertisements without any way for the public to understand that
it is running severe risks.
There is no statutory authority for the FDA to require notification
by maitufacturers that they are even producing a cosmetic product or
that they are introducing a new product or introducing new
ingredielits.
Thus, there appears to be no mechanism for the FDA to assure
that these manufacturers are honestly representing their products
to the public, let alone whether such manufacturers have gone through
and considered reasonable safety consideration before the introduction
of a product.
We have heard testimony which indicates that our present practice
really exposes the American public to severe potential, but severe,
harm given the fact that we now understand the skin to be a part of
the body which readily absorbs material from the outside rather than
being an impermeable membrane.
PAGENO="0357"
351
As the situation now stands, the public must rely on the industry
and its assurance regarding the safety of these products.
I am afraid that the profit motive alone, wheu you consider the
dollars involved in the marketing of a cosmetic product, that the
profit motive alone should make us skeptical of safety assurances from
those who have an interest in the marketing of a product.
The testimony we have heard more than confirms the need for
such skepticism I want to express my appreciation to the various
witnesses who have come before the committee and those who are
here today.
I think that the American public has much to benefit from your
views, and I trust that out of these hearings will come some sub-
stantial improvement in the projection that we can provide to the
public in an area that it really has no way of understanding what
protections it should require; that is, to protect itself from severe
risks of cancer and the like.
Thank you, Mr. Chairman.
Mr. MAGUIEE. Thank you.
Our first witness today will be Mr. Gregory J. Ahart, Director,
Human Resources Division, General Accounting Office.
Gentlemen, we will have to swear you in. Would you please stand?
Do you swear to tell the truth, the whole truth, and nothing but
the truth, so help you God?
[Chorus of I do's from three witnesses.]
Mr. MAOUIRE. Please proceed.
TESTIMONY OP GREGORY J. AEART, DIRECTOR, HUMAN RE~
SOURCES DIVISIOI~, GENERAL ACCOUNTING OPPICE, ACCOM-
PANIED BY ALBERT B JOJOKIAN, ASSISTANT I)IR~CTOR, HUMAN
EESOIfltCES DIVISION, AND JAMES LINZ, SUPERVISORY AUDITOR,
HUMAN RESOURCES DIVISION*
Mr. AHART. Thank you, Mr. Chairman.
I would like to introduce my associates at the table. On my left is
Mr Albert B Jojokian, Assistant Director, Human Resources Divi-
sion, who is responsible for Our work at the FDA.
On my right is Mr. James Linz .on Mr. Jojokian's staff who has
direct responsibility for the work we are going to testify on this
morning.
We are pleased to be here this morning to discuss our report to
the subcommittee entitled: "Cancer and Coal Tar Hair Dyes: An
Unregulated Hazard to Consumers"-HRD--78-22, December 6,
1977-and the results of our broader review of the Food and Drug
Administration's (FDA's) regulation of cosmetics.
Our work has been directed to determining whether: (1) Coal tar hair
dyes and other cosmetics pose an unnecessary hazard to consumers;
(2) FDA has sufficient legislative authority to effectively regulate
cosmetics; an4 (3) FDA has effectively used its existing authority.
FDA's authority to regulate cosmetics in interstate commerce is
derived from the. Federal Food, Drug, and Cosemetic Act, and the
Fair Packaging and Labeling Act.
PAGENO="0358"
3~2
The Food, Drug, and Cosmetic Act requires that a cosmetic be:
Free of substances that may make it injurious; packaged in a safe and
n ondeceptive container; produced under sanitary conditions; and,
labeled with information about the product's manufacturer, packer,
or distributor, and the quantity of its contents.
FDA has authority under the Fair Packaging and Labeling Act to
require that a cosmetic label list the product's ingredients.
Before highlighting the results of our review of cosmetics regulation
in general, I would like to briefly discuss our report to the subcom-
mittee on coal tar hair dyes and subsequent developments.
COAL TAR HAIR DYES
AbQut 33 million women use hair dyes to temporarily or permanently
change their hair color. There is increasing evidence that some colors
used in coal tar hair dyes-the dyes most widely used-may. carry a
significant risk of cancer to users. However, exemptions in the Food
Drug, and Cosemtic Act do not permit FDA to regulate coal tar
hair dye products effectively; they bar FDA from banning or restrict-
ing the use of cancer-causing coal tar hair dyes.
Coal tar hair dyes are divided into three groups-temporary, semi-
permanent, and permanent-depending on the type of coal tar color
used, the method used to apply the dye, and the permanence of the
color.
Colors known or suspected of causing cancer reportedly are being
used in all three types of coal tar hair dyes. Specificially:
Temporary hair dyes may contain coal tar colors shown to cause
cancer :dn laboratory animals and banned by FDA for use in other
cosmetic products.
Temporary and semipermanent hair dyes may contain azo colors
derived from benzidine, a known human carcinogen. Such colors
contain benzidine as a contaminant, and some cf the colors may
break down in the body and release benzidine.
Other coal tar colors available for use in temporary or semiperma-
nent hair dyes have reportedly caused cancer in laboratory animals.
Evidence frcm screening tests or animal studies indicate that several
coal tar colors used in permanent hair dyes, including toluene-2,4-
diamine and 2,4-diaminoanisole, may cause cancer.
Several studies have demonstrated that coal tar hair dye ingredients
are absorbed through the skin and scalp.
Subsequent to release of our report to the subcommittee, newspaper
articles quoted the Cosmetic, Toiletry, and Fragrance Association-
CTFA-as stating that no major hair dye manufacturer has used
benzidine-derived azo colors in their products since 1973. However,
we purchased eight temporary rinses at Rockville, Md., drug stores
containing one or more benzidine-derived azo colors. The manufac-
turer of these rinses is a CTFA member.
Generally, a cosmetic is considered adulterated if it contains any
poisonous or deleterious substance. However, coal tar hair dyes whose
labeling contains a prescribed statutory warning concerning possible
skin irritation and blindness are exempt from these provisions. In
addition, a cosmetic is considered adulterated if it contains a color
additive not approved for safety by FDA under the color additive
PAGENO="0359"
353
pr ovisions of the Food, Drug, and.. Cosmetic Act. Again, ~however,
coal tar hair dyes are exempted.
We recommended that Congress repeal the exemptions for coal
tar hair dyes.
A cosmetic is considered misbranded if its labeling is false .or mis-
leRding. Although coal tar hair dyes. are subject. to FDA labeling re-
quiren~ents, the FDA has not used this authority to require a cancer
warning on labels of coal tar hair dyes containing known human or
animal carcinogens.
We recommended in our report that FDA evaluate safety data on
coal tar hair dye. ingredients and require, where applicable, a cancer
or other appropriate warning statement on product labels.
On January 6, 1978, FDA published in the Federal Register a
proposal to require that labels of hair dyes containing 2,4-diamino-
anisole carry a cancer-warning statement A determination has not
yet, been made on the need for a similar statement on labels of hair
dyes containing other. ingredients suspected of causing cancer.
OTHER COSMETIC HAZARDS
Results of our broader cosmetics review indicat~ that some cosmetic
products may pose significant hazards *to consumers. Specifically:
Ingredients listed in the CTFA Cosmetic ingredient Dictionary
as available for use in cosmetic products include "about 100 ingredients
t~iat the National Institute of Qccupational Safety and Health's
Registry of ~Foxic Effects of Chemical Substances lists as suspected
carcinogens. In addition, 24 ingredients listed in the dictionary are
suspected cf causing birth defects, and 20 may cause adverse effects
on the nervous system', including headaches, drowsiness, and con-
vulsions. Many different routes of exposure and species of animals
were used in the studies referenced by the NIOSH Registry. The
applicability of the, test methods and' results to cosmetics exposure
has not been evaluated.
Certain cosm~etic products including bubble baths,' shampoos,
and feminine sprays have `been associated, with many consumer
complaints.
Hairsprays have been shown to cause a lung. disease which may
lead toward lung malignancy.
FDA has received several reports of vision loss resulting from the
use of microbially contaminated eye makeup 1~tesu1ts of an FDA-
sponsored study published in 1974 showed that about half of the eye
makeup tested after it was partially used by cOnsumers contaii~ed
bacterial. contaitdnation. . "
Serious burns, including at least one death, have been reported
from the use of flammable ~osmetics. ..;~
NEED. ~OR ADDITIONAL LEGISLATIVE AUTHORITY
Before 1972, FDA did not have a formal program'to control cosmetic
products. Since then, FDA has' established several regulations, de-
signed to improve its control o~v-er cosmetics However, because FDA
lacks adequate legislative authority, the effectiveness of many of its
regulatory efforts has been limited. ..
PAGENO="0360"
354
For example, FDA established regulations providing for the regis-
tration of cosmetic manufacturers and packers, and the filing of
cosmetic product ingredient and product experience reports by
manufacturers, packers, and distributors. But FDA does not have
authority to require compliance with the regulations. As a result,
voluntary compliance has been limited. As of December 31, 1977:
Only 896-40 percent-of the approximately 2,200 cosmetic
manufacturers and packers FDA had identified had registered;
Only 768 of the estimated 4,000 to 5,000 cosmetic manufacturers,
packers, and distributors had filed ingredient statements; and
Only 130 of the 4,000 to 5,000 cosmetic manufacturers, packers,
and distributors had filed product experience reports.
An FDA regulation also requires that labeling of cosmetics that
have `not been adequately tested for safety bear a warning to that
effect. However, this regulation cannot be effectively enforced be-
cause FDA does not have authority to require cosmetic manufacturers
to test their products for safety or make their test results avaliable to
FDA.
In addition, many manufacturers have refused FDA inspectors
access to manufacturing records such as qualitative and quantitative
formulas, sales or shipping records, and consumer complaint files
because FDA lacks authority to require manufacturers to permit
access to such records.
Legislation-S. 2365-has been introduced in the 95th Congress to
amend the F.D. & C. Act to provide FDA with additional authority
to regulate cosmetics.
BETTER USE OF EXISTING AUTHORITY
Although FDA's efforts to regulate cosmetic products have been
hampered by the lack of adequate legislative authority, many im-
provements in FDA's regulation of cosmetics could be made under
its existing authority. FDA has authority to:
(1) Inspect cosmetic plants and collect and test cosmetic samples;
(2) Establish manufacturing standards;
(3) Take regulatory action against violative manufacturers;
(4) Restrict the use of hazardous cosmetic ingredients and require
appropriate precautionary labeling on cosmetic products;
(5) Require manufacturers to prove the safety of color additives
used in cosmetics; and
(6) Establish by regulation, tests to be used in evaluating cosmetic
safety~
Our review indicates that FDA has not effectively used its authority
to regulate cosmetics. For example:
(1) FDA has not inspected most cosmetic manufacturers' plants or
sampled most of their products for compliance with the F.D. & C.
Act. Only about half of the known cosmetic establishments were
inspected between 1968 and 1975. Since 1975, FDA identified about
1,000 additional manufacturers, which it had never inspected because
they had been unknown to the agency.
(2) FDA has not established manufacturing criteria to determine
whether adequate methods, facilities, and controls are used in all
phases of manufacturing and distribution of cosmetics. According to
PAGENO="0361"
3J~5
a summary in its. 1975 Compliance Program Guidance Manual, FDA
inspectOrs found during establishment inspections that:
Less than 33 percent of the firms had established raw material
specifications.
Less than 50 percent maintained adequate batch control records.
Less than 15 percent tested equipment for microbial contamination
Only 20 percent tested the effectiveness of the preseryative system
used in their cosmetics.
Only 25 percent maintained an inventory system adequate to
facilitate a recall.
According to an FDA official, about 75 percent of a~ sample of
over 300 firms inspected since 1976 had deficiencies in their manu-
facturing practices.
(3) When violations of the Food, Drug, and Cosmetic. Act are identi-
fied, FDA can seize the violative prOduct, enjoin a manufacturer from
shipping the product in interstate commerce, or prosecute the firm
violating the act. Manufacturers are notified of violations through
issuance of citations, regulatory letters, and information letters,
depending on the nature and severity of the violation.
Between 1974 and 1976, FDA identified over 400 violations of the
cosmetic provisions of the Food, Drug~ and Cosmetic Act, which the
agency found warranted some form of regulatory action, yet only
about 140 regulatory actions-including seizures, prosecutions, injunc-
tions, citations, and issuance of regulatory and information letters-
were taken. Fifty-four of those actions involved one violative product.
I might mentioil that I do not believe any prosecutions were ini-
tiated or citations issued during that period.
(4) Establishing regulations to prohibit or limit the use of an in-
dividual ingredient, or require the use of a specific warning statement
on the label, is an effective way to increase consumer safety with.
regard to a specific product or category of products.
As of January 1, 1978, FDA had established ingredient standards
governing the use of only 11 ingredients in cosmetics, and had required
precautionary labeling only on feminine sprays, aerosols containing
chlorofluorocarbon propellants, and aerosol cosmetics in self-
pressurized containers.
Some ingredients banned ~r restricted for usO in coSmetics in other
count~ries are avail~bi~for use without resti~lction in the United States.
For example, nine ingredients banned for use in cosmetics by a Euro-
pean Economic Community directive adopted by several öountries
were reported to FDA by cosmetic manufacturers as being used in
cosmetics in the United States. A FDA official told us that FDA has
nOt ascertained the basis for restricting the use of these ingredients in
other countries. .
Similarly, the Consumer Product Safety Commission has estab-
lished regulations requiring that specific warning statements be
placed on the labels of household products containing certain toxic
ingredients, but FDA has not establi~hed similar regulations governing
the use of these ingredients in cosmetics.
(5) The 1960 Color Additive Amendments to the. F.D. & C. Act
require FDA to establish regulations listing color additives that are
safe for use in. cosmetics. however, as of December 19~77, the safety
of about 25 color additives available for use in cosmetics had not been
PAGENO="0362"
356
established. In one case-caramel----FDA permitted the continued
use of the color additive for 15 years before a color additive petition
was filed. That petition did not contain all of the required safety
studies and FDA has given the petitioner until 1980 to complete
additional studies.
(6) FDA has not established by regulation specific tests to be used
in evaluating the safety of cosmetic products. Without such regula-
tions, FDA may not be able to use the tests for enforcement purposes.
For example, FDA attempted to prosecute a shampoo manufacturer
for marketing an adulterated shampoo, but the evidence it used to
show that the shampoo was hazardous was not acceptable because it
had not established by regulation the appropriateness of the test used
by the agency to evaluate the safety of the shampoo.
Mr. Chairman, that completes my prepared statement. We will be
happy to answer any questions that you or other members of the
subcommittee may have.
Mr. MAGUIRE. Thank you, Mr. Ahart.
Mr. Lester Brown, special assistant on the subcommittee staff,
will begin the questioning.
Mr. BROWN. Thank you, Mr. Chairman.
Mr. Ahart, on page five of your statement you declare:
Ingredients listed in the CTFA Cosmetic Ingredient Dictionary as available for
use in cosmetic products include about 100 ingredients that the National Institute
of Occupational Safety and Health's Registry of Toxic Effects of Chemical Sub-
stances lists as suspected carcinogens.
You also point out:
* * * 24 ingredients listed in the dictionary are suspect~d of causing birth
defects and 20 may cause adverse effects on the nervous system. * * *
[Indicating]
Is this the document you cite in your testimony as: "The CTFA
Cosmetic Ingredient Dictionary"?
Mr. AHART. Yes.
Mr. BROWN. This is the 1977 issue of the dictionary; is that right?
Is that the latest edition?
Mr. AHART. Yes.
Mr. BROWN. Your research indicates that at least 100 substances
included in this dictionary as ingredients that are available for use in
cosmetics may pose a hazard to consumers; is that correct?
Mr. ~EART. That is correct. They are listed by NIOSH as being
suspected carcinogens.
Mr. BROWN. Are consumers or cosmetic manufacturers provided
with information in this dictionary indicating that these substances
may pose a hazard?
Mr. AHART. I do not believe the dictionary itself would indicate
that to consumers. Of course, consumers probably would not have
access to the dictionary anyway. They would only know what is on
the label of the cosmetic that they purchase.
Mr. ~ROwN. But readers of the dictionary would not be provided
with any information on potential health hazards; is that right?
Mr. AHART. I think that is correct. Let me ask Mr. Linz.
Mr. LINZ. That is correct.
PAGENO="0363"
357
Mr. BROWN. Do you have a list of the ingredients that you cite
in your testimony as being either on the NIOSH suspect carcinogen
list or among those chemicals suspected of causing birth defects, and
adverse effects on the nervous system?
Mr. AHART. Yes; we do. We have a list with us.
Mr BROWN Mr Chairman, I would like to introduce into the record
a copy of the list entitled: "Toxic Effects of Ingredients Listed in the
1977 CTFA Cosmetic Ingredient Dictionary as Reported in the 1976
NIOSH Registry of Toxic Effects of Chemical Substances."
Mr. MAGUIRE. Without objection, it will be included in the record
at this point.
[The list referred to follows:]
PAGENO="0364"
358
* - Toxic Effects of Ingredients Listed
In the 1977 CTFA Cosmttic Ingredient Dictionary
As Reported in the 1976 NIOSH Registry of Toxic Effects
of Chemical Subs lances
Suspected Carcinogens
1. Acacia
2. Acid Blug 9
3. Acid Blue 9 Aimnoniuni Salt
4.. Acid Blue 74 :
5. Acid Green 5 (formerly FD&C Green No. 2)
6. Acid Red 18
7. Acid Red 27 (formerly FD&C Red No. 2)
8. Acid Red 87
9. Acid Violet 49 (formerly FD&C Violet No.. 1)
10. Acid Yellow 73 Sodium Salt
11. Alcohol
12. Basic Orange 2 (IARC a/ Determination: Animal Carcinogen)
13. Basic Violet 10
14. Boric Acid
15. Butyrolactone (IARC Determination: Indefinite)
16. Calcium Carrageenan (IARC Determination: Animal Suspect)
17. Calcium Saccharin (FDA Determination: Animal Carcinogen, Hunan Suspect)
18. Captan
19. Carrageenan (IARC Determination: Animal Suspect)
20. Chloramine-T
21. Chloroacetic acid
22. Cholesterol (IARC Determination: Indefinite)
23. Chromium Oxide Greens (IARC Determination: Animal Suspect)
24. * Coal Tar (NCI Determination: Human Carcinogen)
25. Coumarin (IARC Determination: Animal Carcinogen)
26. D&C Blue No. 1 Aluminum Lake
27. D&C Blue No. 2 Aluminum Lake
28. D&C Blue No. 4
29. D&C Green No. 3 Aluminum Lake
30. D&C Red No. 4 Aluminum Lake
31. D&C Red No. 9 (IARC Determination: Indefinite)
32. D&C Red No. 9 Barium Lake (IARC Determination: Indefinite)
33. D&C Red No. 9 Barium/Strontium Lake (IARC Determination: Indefinite)
34. D&C Red No. 9 Zirconium Lake (IARC Determination: Indefinite)
35. D&C Red No. 17 (IARC Determination: Indefinite)
36. D&C Red No. 19
37. D~.C Red No. 19 Aluminum Lake
38. D&C Red No. 19 Barium Lake
39. D&C Red No. 19 Zirconium Lake
40. D&C Red No. 22
41. D&C Yellow No. 6 Aluminum Lake
42: L~C Yellow No. 8
43. Dehydroacetic acid
44. Dinethoxane
* 45. Dimethyl Sulfate (IARC Determination: Human Suspect)
46. Disperse Yellow 3 (IARC Determination: Indefinite)
47. Ethyl Carbonate
48. Ethylene Oxide (IARC Deteru~nation: Indefinite)
49. Ethylene Urea
50. Ethynylestradiol (IARC Determination: Aninal Carcinogen)
51. FD&C Blue No. 1
52. FD&C Blue No. I Aluminum Lake
53. FD&C Blue No. 2 .
54. FD&C Blue No. 2 Aluminum Lake * *
55. FD&C Green No. -3 ~-. -: ~. - I
56. FD&C Red No. 4 (IARC Determination: Negative)
57. FD&C Yellow No. 6 (IARC Deten?mination: Indefinite)
58. FD&C Yellow No. 6 Aluminun Lake (IARC Determination: Indefinite)
59. Formaldehyde -
PAGENO="0365"
359
60. HG Red No.6 (IARC Determination: Animal Carcinogen)
61. Hydroquinone
62. HydroxystearicAci4
63. Iron Oxides (IARC Determination:-~ Indefinite)
64. Krameria Extract `:
65. Lactose
66. Lead Acetate (EPA 1~eteriniziation: Animal Suspect)
67. Maleic Anhydride
68, Methenamine-
69. Methyihydroxystearate
70. Methyl Methacrylate "
71. Methyl Oleate ` `
72. Methyl Stearate
73. Nylon
74. Oleic Acid
75. Oxyquinoline
76. Oxyquinoline Sulfate
77. Paraffin.
78, PEG-8
79. Phenol (EPA Determination: Animal Suspect)'
80, Phenyl Mercuric Acetate ` *
81. Pigment Red 53 (IARC Determination: Indefinite)'
82. Pigment Red 53:1 (IARC Determination: Indefinite)
83. Polyethylene
84. Polysorbate 80
85. Polyvinyl Alcohol
86. Propyl Alcohol
87. Propylene Oxide
88. `PVP
89. Ricinoleic Acid
90. Saccharin (FDA Determination: Amimal Carcinogen, Human Suspect)
91. Silver
92. Sodium Saccharin (FDA Determination: Animal Carcinogen, Human Suspect)
93. Solvent Red `23 (IARCDeterminatión: Indefinite)
94. Sorbic Acid (EPA Determination: Animal Suspect)
95. Succinic Anhydride
96. ~fhiourea (IARC Determination: Animal Carcinogen)
97. Toluene (EPA Determination: Animal `Suspect)
98. Trichioroethylene (IARC Determination: Animal Suspect)
99. Tristearin
100. Ultramarine Green (IARC DeterinInation: Animal Suspect)
101. Zinc Chloride , ,
,~uspected Teratoge~~
1, Acid Red 27
2. 6..Aminocaproic Acid,
3. BHT-
4. `3utyl Methacrylate
5. Captan.
6, Carbon Dioxide
7. Cetrimonium Bromide
8. Dibutyl Phthalate
9. Dimethyl Phthalate
10. Dioctyl Phthalate
.11. EDTA
12. Ethyl Methacrylate
13. Hexachiorophene
14, Lead Acetate
15. Lithium ChlorLde
16. ME~C
17. Nitrous Oxide
18. Phenyl Mercuric Acetate
19. Retinol
20. Retinyl Palmitate
21. Salicylamide
22. Sodium Chloride
23. Sodium Salicylate
24, .Theophylline
PAGENO="0366"
360
Netvous System Effects
1. Acetone
2. 3oric Acid
3. p-Cymene
4. Dibutyl Phthalate
5. Ethylene Dichioride
6. Hexachlorophene
7. MEK
8. Methoxyethanol
9. Methyl Alcohol
10. Methylene Chloride
11. Methyl Methacrylate
12. Phenacetin
13. Sodium Fluoride
14. Sodium Salicylate
15. Sodium Sulfite
16. Tetrachioroethylene
17. Theophylline
18. Toluene
19. Trjchloroethane
20. Trichloroethylene
a/International Agency for Research in Cancer, World Health Organization
PAGENO="0367"
361
* Mr. BROWN. Mr. Ahart, do you have proof that any of these in-~
gredients are now being used in cosmetic products that are available
to consumers today?
Mr. AHART. Yes; we do. In fact, my staff purchased, within the
last couple of days, several products that do contain some of these
chemicals We would be happy to talk about those We have a list
of those, and also samples available.
Mr. MAGUIRE. Do you have samples with you?
Mr. AHART. Yes; we do.
Mr. MAGUIRE. Could you produce those now?
Mr. AHAwi~. Yes.
Mr. MAGUIRE. Do you have a list of those with you?
Mr AHART Yes, we do have a list that we can supply for the record
Mr. MAGIJIRE. Without bb~ectiQn, the record will be held open to
include this list.
[The list referred to follows:]
Phillips Toothpaste-Sodium Carrageenan, Sodium Saccharin.
Nivea Basis-Coumarin-IARC-Animal Positive includes skin painting study.
Vanseb-T Tar Shampoo-Coal Tar-Known human carcinogen (NCI).
Clairol Kindness Instant Protein Hair Conditioner-PVP-sus~p. carcinogen.
Grecian Formula-Lead Acetate-Suspect Carcinogen and Teratogin is ab-
sorbed through the scalp; (IARC Review: Animal Pô~ltive).
Max Factor Maxi-Wear Nail Guard-Tolvene (EPA Det.-Animal Suspect).
Sally Hansen Creme Hard as Nails with Nylon-Tolvene (EPA Det -Animal
Suspect) Dibut~l Phth late (Susp. Teratogen).
Max Factor Eye P~cil-EHT-~-suspe~ted teratogen.
Revlon Super Crystalline-Tolvene-(EPA Det.-Animal Suspect). Dibutyl
phthalate-susp. teratogen.
Coty Vitamin A-D Soft'NRich Body Lotion-Retinyl Palmitate-Susp.
Teratogen.
Helena Rubenstein Contour Lift Fiim-Carrageenan (IAR~-Animal Suspect).
Max Factor Super Lash Maker-BHT-Suspected Teratogen.
Helena Rubenstein Ultra Feminine Emollient Cleansing Cream EDTA~~Lsus~
pected teratogen.
Clrnique Clarifying Lotion 2-trxchloroethylene-(IARC Det -Animal Sus-
spect) currently under test at NCI.
Mr MAGUIRE Could you read that list for us, Mr Ahart?
Mr. AHART. It is only about 14 products, Mr. Chairman.
It has Phillips toothpaste which contains sodium carrageemn and
also sodium saccharin.
The Nivea and Basis soap contain coumarin which ~s an animal
carcinogen. Available data includes a skin painting study.
Mr. Linz is more familiar with this list than I am. Perhaps 1 should
turn it over to him
Mr. MAGUIRE. Perhaps he could just identify the products and
tell us what is known about each one and what the basis of the suspicion
is in each case. * *
Mr LINz This [indicating] is reported to contain coumarin These
are the Nivea and Basis soaps Coumarin is an animal carcinogen
according to an agency of the World Health Organization One of the
studies upon winch they made the determmtion is a skin painting
study. * * * * *
This [mdicatingj is Max Factor Maxi-Wear sail Guard containing
toluene which EPA suspeets to be a carcinogen.
PAGENO="0368"
~62
Mr. MAcmIRE. Is that the same type of substance included in the
hair dyes?
Mr. LINz. It is not.
Mr. MAGUIRE. It is different?
Mr. LINz. Yes.
This [indicating] is the Coty Vitamin A-D Soft'N Rich Body Lotion
containing retinyl palmitate which is a suspect teratogen, meaning it
may cause birth defects.
Mr. MAGUIRE. Birth defects?
Mr. LINz. Yes.
This [indicating] is a Max Factor eye pencil. It contains BHT as a
preservative, which is also suspected of causing birth defects.
This [indicating] is Helena Rubenstein Contour Lift Film which
contains carrageenin. Again, it is a suspect carcinogen.
This [indicating] is Helena Rubenstein Ultra Feminine Emollient
Cleansing Cream which contains EDTA, another suspected teratogen
This [indicating] is a Max Factor Super Lash Maker which contains
BHT and it is suspected of causing birth defects.
This [indicating] is another nail product, Sally Hansen Creme Hard
as Nails With Nylon, which contains both toluene which is a suspected
carcinogen, and dibu.tyl phthalate, which is suspected ofcausing birth
defects.
We have a Revlon Super Crystalline nail enamel [indicating]
which contains toluene and dibutyl phthalate also.
I think we have gone through the whole list.
Mr. MAGUIRE. I have three up here with me.
This [indicating] is Clairol Kindness instant protein hair condi-
tioner. What do you have on that?
Mr. LINZ. It contains PVP which is a suspected carcinogen.
Mr. MAGUIRE. And this one [indicating] is Vanseb-T Tar Shampoo
with protein.
Mr. LINZ. That contains coal tar, which is a known carcinogen,
according to the National Cancer Institute.
Mr. MAGUIRE. This is Grecian Formula 16.
Mr. LINz. That contains lead acetate, which, according to an
agency of the World Health Organization, is a known animal carcino-
gen and also is suspected of causing birth defects.
Mr. MAGUIRE. A known animal carcinogen and evidence of birth
defects?
Mr. LINZ. Yes.
Mr. MAGUIRE. And there is evidence that it is absorbed through the
skin?
Mr. L~LNZ. Yes.
Mr. WALGREN. I notice, Mr. Chairman, that under the Grecian
Formula 16, it says: "Used by Millions of Men."
Mr. MAGUIRE. I am afraid to go home and look in the cabinet.
Mr. Ahart, in your statement, you indicate that you had purchased
eight temporary hair dyes at random and that all of these contained
one or more benzidine-derived azo colors.
We have been told by the CTFA representative that the temporary
hair dyes do not contain any of these substances which we are
discussing.
PAGENO="0369"
363
In' view of that statement about the absence of these derivatives
in hair dyes, what conclusion would you come to about the statement
as against the facts as you found them when you purchased the hair
dyes?
Are we talking here about something that is misleading, or is there
any possibility that they could b~ deliberately misleading? What is
your judgment on this?
Mr. AHART. I do no know if `it is' deliberately misleading or not,
but it is certainly misleading. Whether or not the people making the
statement had information on the ingredients used in all the products,
I do not know.
The ,product in question,' I think-w~ have it here-is a Roux
brand, Fanciful Rinse It is made by a member of the CTFA However,
this `manufacturer had not' submitted the ingredient statement to
FDA under the voluntary' program. So, unless the manufacturer dis-
closes the ingredients, it may be' that no one `would `know.
I do not know if that ingredient is listed on the label or not.
Mr. Linz, is it?
Mr. LINz. It is.
Mr. AHART. But you would have to look at the label or get the
information from the manufacturer.
Mr. MAGUIRE. The bottom line, I take it, is that the public is
being deceived on this' particular point by CTFA. They say that
there is not any of the stuff in the `temporary hair dyes. Then you go
out and find, in 8 cases-and I guess it was 8 out, of 8, was it not?
Mr AHART It was eight different kinds of this [indicating] particu-
lar product or the same brand of product in different colors with the
same thing in it.
Mr. MAGUIRE. They all had benzidine-derived azo colors?
Mr. ARART. That is correct.
Mr. MAGUJEE. You report that hair sprays ha~ve been shown to
cause a lung disease which may lead toward malignancy.
What is that disease and how widespread is it?
Mr. AHART. Mr. Linz, could you answer that? This was a study
made out in Utah, a carefully designed study.
Mr. Lixz. It is a disease known as pulmonary thesaurosis. I am not
sure whether that is the correct pronunciation or not.
Mr. MAGUIRE. We will make sure that we spell' that properly.
Tell us about it.
Mr. LINz. The symptoms are a cough and shortness of breath.
It can lead-
Mr. MAGUIRE. It looks like pulmonary thesaurosis; how is that?
`Mr, L1NZ. You did better than I did.
It is characterized by spots' on the'chest X-ray, shortness `of breath,
and a mild cough. It can lead to more severe changes leading toward
lung malignancy.
Mr. MAGUIRE. How widespread is it?
Mr. LINZ. This was based on a survey of hair dressers in Utah.
The NIOSH conclusion was based on a sample of" 262 student cos-
metologists and 213 graduate cosmetologists `from Utah. They were
compared to a group of 569 people matched by age, history, and
region.
24-600 0 - 78 - 24
PAGENO="0370"
364
The prevalence of the disease seemed to be 22.5 percent in graduate
beauticians. They say that is a significant increase over what was
seen in the student cosmetologists or the control group.
The highest prevalence of the disease was in small salons were there
was not adequate ventilation, the report says.
Mr. MAGUIRE. You referred to ingredients being sold in this
country which are banned in other countries, Mr. Ahart.
Has the FDA tested and approved as safe those ingredients?
Mr. AHART. I do not think it is a question of testing or approving
them as safe. They are banned in other countries. FDA has never
gone to the other countries and found the basis for the ban in the
other countries or the restriction on their* use in other countries.
Mr. MAGUIRE. What are some of those ingredients?
Mr. AHART. I have a listing here. Several are banned by the Euro-
pean Economic Community.
The fist is antimony potassium tartrate which is used in hair
tonics, dressings and other grooming aids. Barium sulfide is another
which is used in shaving preparations.
There is a chemical product called brucine, which i~ also used in
preshave and aftershave lotions and feminine sprays, underarm
deodorants and other personal cleansing products, as well as hair
tonics, dressings, and hair grooming aids.
Cantharides is also used in hair tonics and dressings. Hydroxyanisole
is used in lipstick, moisturizing creams, lotions, powders, sprays, and
mascara.
Iodine, which ~is used in personal cleanliness products is another.
Phenol, which is used in hair tonics, dressings, and other grooming
aids and douches and skin care preparations is another as well as
trichresyl phosphate, which is used in nail polish or enamel.
The last one I have here is tetrachloroethylene which is used in
eye makeup preparations.
Mr. MAGUIRE. Without objection, that list, in its entirety, will
appear in the record at this point.
[The following material was received for the record:]
PAGENO="0371"
365
~ turer!
~
Economic Co~tiit Directive
Antim~Lpotassiumtartrate (1 product).
Hair tonics, dressings,, arid other grooming aids at conlentrations
of 0.1 percent or less.
~arium..sulf~,4~ (1 product)
Shaving preparations at concentration of 10 `to 25 percent.
Bruethe (6 products)
Preshave and aftershave lotions, feminine sprays, underarm
deQdorants, ~ind other persenal cleanliness proiiucts,. and
hair tonics, dressings, and other hair grooming aids at
cotations of 0.1 percentbr less. -
Cantharid~s (1 product)
Hair tonics, dressings, and other hair groomthg aids at
concentrations of 0.1 percent or less
`~o~2~ (5 products)
Lipstick, moisturizing creams, lotions, powders, and sprays,
and mascara at concentrations of 0.3. pertexit or less
iodine (1 product)
Personal cleanliness products at concentrations of I. to 5'percent.
~ (4products)
Hair tonics, dressings, and other grooming aids, skin care
preparations, and douches at concentrations of 1 percent or
less.
Tricresyl ph ,pha.te (7 products)'
Nail polish and enamel at' concentrations `of S percent or less.
Tetrachloroeth~y~ene (I product)
Eye makeup preparations at concentrations of 50 percent or less.
PAGENO="0372"
366
Mr. MAGIJIRE. Mr. Ahart, you have made serious charges about
FDA's failure to use its existng authority. Would you care to speculate
on why that authority has not been used?
Mr. AHART. `I here are probably several reasons. I think until
recently there has not been a great deal of public pressure or public
information or public suspicion, I might guess, about the danger of
cosmetic products. I think FDA, over the years, has to some degree,
responded to pressure and public information.
if cosmetics were not being touted today, they would not get as
much emphasis as other things that FDA is being pressured on.
Second, there may be a problem in the adequacy of resources to do
the kind of things that need to be done to cover the inspections and
so on.
Also, there may be some discouragement among FDA people be-
cause they do have rather limited authority in the cosmetic area.
There might be some discouragement to really put a lot of pressure
into this area, particularly if there is no public complaint or public
response.
So, I think it is a combination of all of those factors. FDA could
probably speak better than I could to the reasons for that.
Mr. MAGUIRE. Would you comment further on your statement
that FDA has not established, by regulation, specific tests to be used
in evaluating the safety of cosmetics?
I am particularly concerned, obviously, about the implications of
that for enforcement.
Mr. AHART. As I pointed out in my statement, FDA is handicapped
when it takes enforcement action if there is not an established test
by regulation to evaluate the safety of the products. It cannot very
well go into court on some basis other than something established by
regulation and use that as the basis for enforcement.
So, unless those regulations are in effect, it is very difficult for them
to go after anyone on the basis of safety.
It is also difficult in this case because in the case of cosmetics there
is no premarket clearance required. The burden of proof as to the
lack of safety of the product really falls on FDA rather than on the
manufacturer as it would in the case of drugs and other things.
So the burden of proof is with the Government, and that makes a
difficult problem as well.
Mr. MAGUIRE. So, first of all, FDA has not used its existing author-
ity. Specifically they have not issued regulations in cases, even under
the current very weak law, they might have done so; is that correct?
Mr. AHART. That is correct.
Mr. MAGUIRE. Would you say, in addition, that even if they do
issue regulations and do use that authority, that in some cases they
have no further authority to require compliance with those regula-
tions? Would that be a correct statement as well?
Mr. AELART. They would have the authority to require compliance
had they established the regulation and carried the burden of proof
showing that a product was not safe. Then they would have authority
to ban the product and get an injunction and enjoin the manufacturer
from putting it on the market and so on.
But the burden of proof would still be on FDA to prove the lack
of safety of the product as opposed to what is done in other cases,
PAGENO="0373"
367'
to put the bnrd~ti on the manufacturer or distributor or packager
to show that the product being put out in the public arena is safe
under the conditions of use specified. S
Mr. MAGUIRE. Would that be your recommendation with respect
to how cosmetics ought to be handled? S
Mr. AHART. That the burden of proof should be on the manu-
facturer? Yes, Mr. Chairman. S
Mr. MAGUIRE: Mr. Waigren, do you have some questions?
Mr. WALGREN. It is true that the~ FDA has attempted to provide
some kind of regulation in this area, and yet' they have run into a
lack of, at least, cooperation from the industry; is that not correct?
Mr. AHART. It is correct in the sense that the regulations' that they
do have ~re generally the ones that the industry would comply with
only on a voluntary basis in terms of the filing of the ingredient
statements, the regtsterirxg of manufacturers' plants, and filing product
experience reports. `
They do have the regulations `out. So there is a degree of compliance.
It is a verysmall percentage of the universe in terms of the number of
establishments. Probably a larger part of the universe, in terms of
the quantity of products. , S
But, no, they do not have the authority to force compliance with
those regulations.
Mr. WALGR~N. But the' FDA has' asked cosmetic manufacturers to
regi~'ter with them and relatively law have?'
Mr. AHART. I believe about 40 percent have. `
Mr. WALGREN. And the FDA has asked manufacturers to file
ingredient statements with them and relatively few have; is that
correct? S
Mr. AHART. That is correct. `
Mr. WALGREN. And the FDA has asked manufacturers to file
experience reports, and almost no one has; is that correct?
Mr. AHART. That is correct.
Mr. WALGREN. We do not even know how many xuai~ufacturers
there are. There' is a guess between 4,000 and 5,000; ~is that right?
Mr. AHART. That is correct. That figure includes manufacturers,
packers, and distributors. ., S
Mr. WALGREN. And the FDA has actually" made some onsite
attempts to inspect consumer complaint files and have been refused?
Mr. AHART. That is correct. They do not have the. statutoi5r' au-
thority to demand access to those files.
Mr. WALGREN., That is all I have, Mr. Chairman.
Mr. MAGUIBE. In summary then, Mr. Ahart, there needs to be,
some substantial improvements, I ~take it, in your view, in the way
that we handle exposure to cancer-causmg or potential ca~cer-causrng
substances in cosmetics? S
And, in particular, we need to improve the way the FDA operates
in this area; is that correct? S
Mr. AHART. I think in two aspects. We need to `improve the~ law
to give the FDA more authority to do the kinds of things that need
to be done and then FDA, in turn., has to take that burden and use
its authority to protect the public in this area
Mr. MAGIYIRE. Would you care to go into more detail at this point
on your suggestions as to' what new authority FDA should have from
this Congress?
PAGENO="0374"
368
Mr. AHART. We will be shortly releasing a draft report to FDA
for comment which will make specific proposals for legislative change
and what kind of authorities they should have.
I think it might be better to wait and get their reaction as to how
they feel about it before we would want to state specifically what
they should be.
Certainly registration of manufacturers, packagers, and distributors
would be appropriate; and a requirement of mandatory filing of
ingredient statements would be appropriate.
A shifting of the burden from the Government to the industry
would be appropriate. There will be other things. Certainly we ~i ill
be recommending these.
* Mr. MAGUIRE. Thank you very much, gentlemen, for your
testimony.
Our next witness is the Honorable Donald Kennedy, Commissioner
of the Food and Drug Administration.
Gentlemen, would you p]ease rise so I can swear you in.
Do you swear to tell the truth, the whole truth, and nothing but
the truth, so help you God?
[Chorus of I do's from four witnesses.]
Mr. MAGUIRE. Commissioner, would you introduce your associates?
TESTIMONY OP HON. DONALD KENNEDY, Ph. D., COMMISSIONER,
FOOD AND DRUG ADMINISTRATION, PUBLIC HEALTH SERVICE,
DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE; AC-
COMPANIED BY: RICHARD COOPER, CHIEF COUNSEL, FDA; HOW-
ARD IL ROBERTS, Ph. D., DIRECTOR, BUREAU OF FOODS, FDA;
AND ROBERT L SCHEUPLEIN, Ph. D., CHIEF, DERMAL AND OCU-
LAR TOXICITY BRANCH, DIVISION OF TOXICITY, BUREAU OP
FOODS, FDA
Dr. KENNEDY. I would be happy to.
To my extreme left is Dr. Howard Roberts, Director of the Bure au
of Foods. rro may immediate left is Robert Scheuplein, a toxicologist
in the Bureau of Foods scientific staff. To my right is Richard
Cooper, the Chief Counsel of the Food and Drug Administration.
Mr. MAGUIRE. Thank you. You may proceed.
Dr. KENNEDY. Mr. Chairman, I will not read all of my statement
to you. We will submit it~ and other materials for the record.
Mr. MAGUIRE. Without objection, your testimony will appear in its
entirety following your summation [see p. 373].
Dr. KENNEDY. I might say that we are very glad to be here today
to discuss our mutual concerns about potentially dangerous chemical
in cosmetics.
The Food, Drug, and Cosmetic Act is designed to afford protection
to the public from harmful foods, drugs, and cosmetics. We agree
with you that it has long contained a serious loophole.
We lia~e, in the past, asked repeatedly for legislation to close that
loophole. As you know, in enacting the 1938 provisions of the act,
Congress exempted the coal tar hair dyes from the adulteration pro-
visions as long as products containing these chemicals bear the
PAGENO="0375"
369'
caution `stat~ment prescribed, by `section 601(a) of the act and advise
that a. patch test be mad~ prior to use.
As you probably know, one of the most important ingredients in
hair dyes which you have been discussing in these hearings, Mr.
chairman, is paraphenylenediámine, a known sensitizer.
It was, in fact, the sensitization problem which is associated with
that compound that led to the exemption. It has the effect of exempt-
ing products containing coal tar hair dyes entirely from the adultera-
tion provisions of the act for any problem they present
I will be prepared, Mr. Chairman, if you would wish us to, to go
in a little bit to the chemistry of hair dying and to the kinds of prob-
lems that are now encountering with coal tar hair dyes.
I tbink'~I will let that,go unless `you ask for it at the end.
Suffice to say for the moment that one can roughly divide the
compounds used in permanent hair dyes into a class of largely ,meta
cOmpounds which are used as coordinators, couplers, modulators;
and a group of pyra compounds which include pyraphenylenediamine
and pyralenediamine, which are the primary oxidizing agents.
it is members of the first group of compounds which have produced
the first results off the .Natioxi~1 Cancer Institute's testing line.
As you know, we have `proposed mandatory , warning statements
for one of these, the compound 4-methoxy-m-phylenediame [4-MMPD]
That is a' compound"that you will also hear referred to as 2,4-
diaminoanisole.
`In this same class of compounds is one which the National Cancer
Institute has told us and you that they are ubout ready to give us a
final report on, that is, 2,4-tolueñediamine, although our information
indicates that is nor used any longer if positive results are confirmed.
NCI will be giving that to us in March. We will include it in Our
label warning requirement proposal.
We do have, and are submitting to you-you probably will have
had it from other sources anyway-a chart that indicates the other
chemicals in th'is hair dye group that are `being te~'ted, and indications
to which it appears that they will or will not prove to be carcinogenic.
I should add one incidental note, Mr. Chairman. Coal tar colors
are mariufacturered from a basic petrocheniical ingreçlient, benezine
toluene and napthalene. .~ .` `.
At one tnme these chemicals were produced almost entirely from
coal tar So, the hair dye products were named coal tar hair dyes
An increased recent demand for these feed stocks and other indus-
trial uses httd Iea~d to an alternate source of `the synthesis from petro-
leum But ~i~' does not make any differeiice at all whether coal tar
colors are, derived from coal tar or `petroleum. `They are chemically
identical and they receive 4denticai. regulatory treatment.
A few epidemiological studies of human exposure to hair dye
ingredients have been conducted recently. You have heard about some
of this research and you know that it provides conflicting data,.
In Order to resolve some of the issues, FDA,,. and the, National
Institute of `EnvirOnmental Health Sciences a~'d the Oan~er Institute
are going to plan a workshop to evaluate hair dye products all together
In addition, our interagency working group on special problems in
cancer epidemiology, composed of scientists from our agency and the
National Cancer Institute, is preparing an assessment of the epi-
PAGENO="0376"
370
demiology of hair dye usage. Their report will be part of materials
considered by the workshop.
I might just add that in our review at this time it is hard to draw
any definite conclusion from the epidemiological data on one side or
the other.
We intend to require warnings on any coal-tar hair dye when
evidence of possible danger to the public so warrants them. But our
ability to protect the public, particularly from the risk associated with
long-term use of hair dyes, will continue to be severely limited until
Congress repeals the exemptions for coal tar hair dye products.
We have long stated that the coal tar exemptions of section 601 (a)
and (e) and 602(e) should be repealed.
I hope these hearings, Mr. Chairman, will help to stimulate con-
gressional interest in accomplishing this legislative change.
Turning now to benzidine-derived dyes, these are direct dyes that
have also been implicated as carcinogenic because it may not be
possible to make them without their containing some free benzidine
which, as has been pointed out to you before, is a known carcinogen.
Under the current law we cannot require cosmetic manufacturers to
report their formulations. We must rely instead on our voluntary
reporting program and on inspection of labels of marketed products.
For that reason, subject to these defects, we really cannot be sure
how extensive benzidine-derived hair dye ingredients are being used
today. But we are trying to find out.
The committee has also been interested in another problem that
troubles us quite a lot; it has to do with N-nitrosodiethanolamine,
which I will call NDELA. Recent studies indicate that this chemical
may be present in many cosmetics, in amounts in some single analyses
that we find quite alarming.
Triethanolamine, diethanolamine and related amines are widely
used as cosmetic ingredients, particularly in shampoos, bubble bath
products, and all types of creams and cream lotions.
Triethanolamine, when reacted with a fatty acid to form a soap,
is an emulsifier that permits the mixing of oil and water. Triethanol-
amine is also present in cosmetics as the salt of a number of detergents
and foaming agents. Diethanolamine is primarily a component of a
wide variety of diethanol fatty acid amines that serve as foam boosters,
stabilizers, and conditioners in shampoos and related products~
The difficulty with the NDELA problem, and in fact of N-nitros-
amines in general, whether one fin.s them in products or iii biological
systems, is that very often they form as a consequence of reaction
between components of a product; that is, they are not there in the
actual, manufacturing of the product.
In fact, the N-nitrosating agents, the nitrites and the nitrates,
which react with the amines which I have just described, many enter
the cosmetic as a contaminating agent, a component of another
ingredient.
For that reason, it is a little difficult to keep track of these circum-
stances which predictably give rise to the product of N-nitrosamines.
Butwhatever the source of the nitrate or nitrite or othernitrosating
agents-and it may be either a nitrite or a nitrate-the nitrosating
agent may react with the amine in the presence of, ~ reducing agent
to form N-nitrosamines.
PAGENO="0377"
371
This reaction can happen during the manufactui'~r or' the storage
of a product, and it' may be very, sensitive to the differences in
formulation.
The analyses for the detection of NDELA at the levels that are
necessary to evaluate its presence in human cosmetics are very, very
new. You will have heard from Dr. Fine abouthis remarkable progress
in developing such a method.
As soon as we heard late last spring of that new technology, we
installed it as quickly as we could in the Agency. We are now tooled
up to do this kind of~ analysis ourselves.
In recent weeks we have'confirnied Dr. Fine's findings of NDELA in
high levels in a couple of products We are extending this analytical
program to conduct `a surveillance of NDELA contamination in
commercially marketed cosmetics. We are also conducting laboratOry
studies on `the skin penetration of NDELA, which is another impor-
tant issue in estimating its human hazards.
We have also urged the cosmetic industry to accelerate its in-
vestigation of the origin of the nitrosamine contamination in cos-
metics and the best means of reducing or eliminating it. FDA will
support such efforts whenever possible. We have urged the industry
to pay very heavy attention to this problem.
Finally', I w'as requested to discuss the chemical, 1 ,2-Dichloroethan,
which is also known as ethylene dichioride. There is preliminary data
from the NCI bioassy that suggests tha't it produces cancer in test
animals. .
So far as we know it is no longer used in cosmetics. It was once a
component in a few nail enamels, but according to' our voluntary
registration data-and again you know of the defects in that-these
products that we knew contained it were reformulated in 1975.
It is used as an aid in food processing, often as a fungicide. Under
the conditions of the use of this chemical, and the nature of the
products in which it is permitted,, the amount of ethylene dichloride,
if any, that remains in the finished food, is extremely small
But we are reevaluating the food additive uses in a lot of the NOI
data, and we.will have a regulatory response to offer if one is necessary,
as soon as that analysis is complete.
The fumigant uses are the responsibility of the EPA, and through
the four agency coalition we have informed the EPA of the need to
reevaluate those uses.
I might add that there now fortunately is an effective mechanism
for sharing such information. The Interagency Regulatory Liaison
Group, composed of ourselves, EPA, OSHA, and CPSC tries to inter-
act to improve the working coordination among the four agencies in
matters related to the protection of the public and the environment
from the adverse effects of toxic and hazardous substances.
Let me just summarize, Mr. ~Chairman, by `saying that we have
tried to focus in our testimony on the several different types of
chemicals which have one common element; they are already marketed
products that are the subject of safety concerns generated by our new
capacity to produce' esti~nates of hazards that we' were unable to
`reach before. , ` ..
I believe it is important for Congress and the public to understand
that questions about the safety of these substances, especially new
evidence of carcinogeniOity, will continue to come to our attention.
PAGENO="0378"
372
This process of questioning accepted products and chemicals, sub-
jecting them to our increasingly sophisticated analytic and testing
methods, and dealing with new conclusions about their safety, is, I
think, a terribly necessary and socially useful process.
It does, however, produce a lot of public alarm when compounds or
materials that have come to be regarded with a certain trust-and
even affection-come up presenting problems. But I think we need to
move vigorously in the direction of taking regulatory action. Of
course, we hope for the strongest congressional support that we can get.
I would conclude by urging again that the exemptions of coal tar
hair dyes from the adulteration provisions of the act be repealed.
We are reviewing other aspects of the cosmetic provisions, some of
which were mentioned by the GAO people in their testimony earlier
this morning.
We hope for revision to cure such infirmaties as the lack of a
requirement that the industry conducts safety testing, the lack of
authority to require submission of safety substantiation data or other
reports and records, the lack of authority to require adverse reaction
reporting, the lack of authority to require even the submission of
product formulations or registration of cosmetic manufacturers, and
our severely limited inspection authority.
As the law now stands, cosmetics are the only products for which
the legal burden rests on FDA to prove a hazard to the public, rather
than on the industry to demonstrate that their product has been
tes ted in accordance with currently accepted methodology, and that
it is safe.
[Dr. Kennedy's prepared statement follows:]
PAGENO="0379"
373
STATEMENT
BY
* ~* DONALD KENNEDY
COMMISSIONER
* ~FOOD AND DRUG ADMINISTRATION
PUBLIC HEALTH SERVICE
DEPARTMENT O~ HEALTH, EDUCATION, AND WELFARE
BEFORE THE
SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS
COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE
HOUSE OF REPRESENTATIVES
FEBRUARY 3, 1978
PAGENO="0380"
374
Mr. Chairman:
I am pleased to be here today to discuss our mutal concerns about
potentially dangerous chemicals in cosmetics. Recent findings that
some chemicals in hair dyes are carcinogenic in animals, have made
this a subject with considerable national visibility.
The Federal Food, Drug, and Cosmetic Act, which is designed to afford
protection to the public from harmful foods, drugs, and cosmetics,
has long contained a serious loophole. In enacting the 1938 provisions
of the Act, Congress exempted the `coal-tar hair dyes from the
adulteration provisions as long as products containing these chemicals
bear the caution statement prescribed by section 601(a) of the Act and
advise that a patch test be made prior to use. The statement also includes
a warning against the use of these types of dyes on eye lashes ~and eye
brows. One of the most important ingredients in hair dyes is
paraphenylenediamine, a known sensitizer, that is, a product which
induces allergic reactions. However, this ingredient is essential in
the oxidation (permanent) hair dyes; hence, the exemption was
originally granted subject to labeling requiring a patch test.
Coal-tar dyes were also exempted from the color additive reguirements
of the Act.
Coal-Tar Hair Dyes
Coal-tar colors are manufactured from the basic chemicals benzene,
toluene, and naphthalene. Because at one time these chemicals
were derived almost exclusively from coal-tar, the hair dye
products were named `coal-tar' dyes. Increasec: recent demand
PAGENO="0381"
375
for benzene, toluene, and naphthalene has led to an alternate sou~ce
of the hair dye chemicals from petroleum. Whether "coa-l~tar" colors are
derived from coaltar or petroleum, they are chemically Identical.
We believe that they should therefore receive identical regulatory
treatment~
In 1972 the FbA asked the National Cancer Institute (Nd) to test some
of these chemicals in its çarcinogenesiS bioassay program. Reports about
the likely hazard of certain chemicals in permanent hair dyes have been
the focus of our attention over the past several months. Results are
now available for a few of these chemicals and should be available
shOrtly on the remaining ones. 4~methoxy~~'pheflYlenediamine (4-MMPD)
sulfate which is also referred to as 2,4-diaminoanisole (2,4-DAA)
has been determined to be carcinogenic in two species of laboratory
animals. These findings apply equally to the free amine, the form
ol~ the dye which is present on the scalp du~ing haiV~ dying. As you.
kflow, any chemical which has yielded positive results In such tests
must be viewed as a possible hazard to humans. Because human and
animal testing have demonstrated 4-MMPD penetrates the skin, the
finding that It is a carcinogen is very disturbing.
Although the Agency cannot ban 4..MMPD, we did propose a regulation to
require a warning On the label of products that contain this chemical.
This, coupled with ~ requirement for warning `posters in beauty salons,
will alert people' to the hazard ~o that aonsumers can make an informed
choice about whether to use these products.
PAGENO="0382"
376
We intend to take necessary regulatory action for any other chemical
component of coal-Star hair dyes that may be absorbed during use and that
we determine poses a cancer risk based on our review of the results of
the NCI `carcinogenic bioassay testing program or any other appropriate
tests. Although our information indicates that 2,4-toluenediamine (2,4 IDA)
is no longer used, if positive results are confirmed we will include it
In our label warning requirement proposal. Preliminary data on other
chemicals being tested indicate that several others may be added to the
warning requirements in the near future.
A few epidemiological studies of human exposure to hair dye ingredients
have been conducted recently. This research provides conflicting data
and In order to resolve some of the issues FDA, NIEHS, and NCI are
planning a workshop to evaluate hair dye products. In addition, our
Interagency Working Group onSpecial Problems in Cancer Epidemiology,
composed of scientists from NCI and FDA is preparing an assessment of the
epidemiology of hair dye usage. Their report will be a part of material
considered by the workshop.
We intend to require warnings on any coal-tar hair dye when evidence of
possible danger to the public so warrants them. But our ability to
protect the public, particularly from the risks associated with long-term
use of hair dyes, will continue to be severely limited until Congress
repeals the exemptions for coal-tar hair dye products. We have long
stated that the "coal-tar' exemptions of sections 601(a) and (e), and
602(e) should be repealed. I hope these hearings will help to stimulate
Congressional interest in accomplishing this legislative change.
PAGENO="0383"
377
zidjjie-Derived Dyes
Our attention has also focused on se~ieral benzidiné.derlved dyes
that may still be ~Used in nonpermanent hair dyes. These "direct"
dyes have also been tmplicated as carcinogenic agents, because it may
not be possible to make them without containing some free benzidine,
a known carcinogen. Under current law we cannot require cosmetic
manufacturers to report their formulations, and we must.rely on our
voluntary reporting program and inspection of' labels of marketed
products. Thus, we are tiot sure how extensively benzidine-derived
hair dye ingredients are being used today; We are now determining
whether these ingredients are still present in marketed hair dyes.
N-Nitrosodiethanol~mine
Another animal carcinogen, n-nitrosodiethanolamine (NDELA), Is also
being studied by the Agency. Recent studfes indicate that this chemical
may be present in many cosmetics through chemical reactfon of an
amine with a nitrosating agent in the finished product.
Triethanolamine, diethanolamine and related amines are widely used as
cosmetic ingredients, particularly in shampoos, bubble bath products,
and all types of creams and cream lotions. Triethanolamine, when
reacted with a fatty acid~ to form a soap, i an emulsifier that permits
the mixing of oil and water. Triethanolamine is also present in
cosmetics as the salt of a number of detergents and ~ôaming agents.
Diethanolamine is primarily a. compánent of a Wide varL~ty of diethanol
fatty acid amides that serve as foam bodsters, stabilizers, and
conditioners in shampoos and related products.
PAGENO="0384"
378
We know little about the formation of nitrosamines in cosmetics from
these amines. Nitrosating agents such as nitrites and nitrates are
not usually used as cosmetic ingredients, but may enter a cosmetic
as a "contaminating" component of another ingredient. Other nitrosating
agents may also contribute to the presence of NOELA. Whatever the
source of the nitrite, nitrate, or other nitrosating agent, it may
react with the amine in the presence of a reducing agent to form
nitrosamine. This reaction may occur during the manufacture or storage
of the product.
Although analytical methods for identification of nitrosamines have
been available for some time, those for the analysis for NOELA at the
required levels of detection are quite new. Furthermore, little is
known about the hazard of NOELA under conditions of its presence
in cosmetics. These matters are now being studied by the Agency.
The Agency has taken several steps to obtain the scientific information
necessary to resolve the NDELA issue:
1. We have established an analytical program to determine the
extent of NDELA contamination in cosmetics. This will be used
to conduct a broad surveillance of the NOELA contamination in
commercially marketed cosmetics.
2. We are conducting laboratory studies on the skin penetration
of NOELA. The Bureau of Foods and the National Center for
Toxicological Research have also begun developing test
protocols in case additional animal studies are needed.
PAGENO="0385"
379
3. We have urged the cosmetic industry to accelerate its
investigations of the orign of the nitrosamine contamination
in cosmetics and the best means of reducing or eliminating it.
FDA will support such efforts whenever possible.
l,2-Dichloroethane (Ethylene Dichloride)
Mr. Chairman, you asked specifically that I discuss. the chemical
1,2-dichioroethane, also known as ethylene dichloride. Preliminary data
from an NCI bioassay suggest that this chemical produced cancer in test
animals. We believe that it is no longer used in cosmetics. It was
once a component of a few nail enamels; according to our voluntary
registration data, however, these products were reformulated in 1975.
In addition, It is used as a food processing aid. There are 11 approved
food uses including solvents, adhesives, spice extracts, and fumigation
of certain grains and grain mill machinery. Under the conditions for use
of this chemical, and the nature of the products in which it is permitted,
results in only a negligible quantity of ethylene dichioride if any
migrates to finished food products. We are now reevaluating these food
additive uses in light of the MCI data. Bureau of Drugs scientists have
checked their records and do not find 1,2-dichloroethane to be listed as
either an active or inactive ingredient in drug products. The fumigant
uses are now the responsibility of EPA. We have advised EPA of the need
to reevaluate these uses of this compound.
24-600 0 - 78 - 25
PAGENO="0386"
380
As you know, NCI alerted us to their verified findings on this chemical
last November. In addition to taking steps to evaluate this information
within FDA, we have also shared the information with other agencies
responsible for the regulation of toxic substances. Fortunately, there
is now an effective mechanism for sharing such information. You are
probably aware of the steps taken some months ago ty the FDA, EPA, OSHA,
and CPSC in establishing the rnteragency Regulations Liaison Group (IRLG).
This is an effort to improve substantially the working coordination among
these four agencies in matters relating to protection of the public and
the environment from the adverse effects of toxic and hazardous substances.
The IRL~ is aware of the preliminary data on l,2-dichloroethane, and any
action FDA decides to take will be coordinated with that of the other
three agencies in that group.
Should we conclude that ethylene dichloride poses a human health hazard
in products we regulate,we will takeappropriate regulatory action,
including delisting of approved food additive uses.
Conclusion
My discussion today has focused on several different types of chemicals
which have one common element--they are all the subject of safety
concerns generated by new scientific information. I believe it is
important for Congress and the public to understand that questions about
PAGENO="0387"
381
the safe use of substances, especially new evidence of earcinogenicity,
will continue to come to our attention. This process of questioning
accepted products and chemicals, subjecting them to our increasingly
sophisticated analytic and testing methods, and dea'ing with new
conclusions about their safety is a beneficial one. Continuing reevaluation
in the light of new evidence and new st~ndards must be a routine part
of FDA's work. The regulatory changes that result from this process
should be taken as a sign that the system is working and not, as has
so often been the case, as a cause for accusation and alarm.
Rapid changes in scientific knowledge and capability often requires
that legislative authority be updated. Once again, I would like to
urge that the ex~emptions of coal-tar hair dyes from the adulteration
provisions of the Act be repealed. We are reviewing other aspects of
the cosmetic provisions of the Act to determine the need of change.
Areas we are looking at include: lack of a statutory requirement that
the industry conduct safety testing and lack of authority ~to require
submiss ion of safety substantiation data or. any other records and
reports, lack of.authority to require adverse reaction reporting, lack
of authority to require even the submission of product formulations or
registration of cosmetic manufacturers, an~severely limited inspection
authority. As the la~i now stands, cosmetics are the only product
for which the legal burden rests with FDA to p~ove a hazard to
the public rather than on the industry to demonstrate thatthelr product
has been tested in accordance with currently accepted methodology and Is
safe. .
Thank you Mr. Chairman. I will be pleased to answer anyquestions you
and the other members of the Subcomittee may have.
PAGENO="0388"
382
Mr. MAGUIRE. Thank you very much, Commissioner.
Mr. Brown?
Mr. BROWN. Dr. Kennedy, as a scientist, do you believe that a
product which has been found to be a mutagen under the Ames
test and other short-term mutagenicity tests and which may be
absorbed through the skin, should be placed in a cosmetic product?
Dr. KENNEDY. I think probably not, Mr. Brown. As you know,
the concordance between the Ames test and long-term tests, that is,
animal tests for carcinogenicity is good, but not perfect.
I think there are serious questions as to whether the Ames test is yet
ready to be used as the final arbitrator of regulatory action. I think it
should be used, and is now being used as a means to identify and
prioritize those compounds that need serious attention from limited
testing facilities in other areas.
I myself hope that enough short-term tests will be developed so that
a serial-battery of such tests will eventually be able to service and
relieve us of some of the terrible resource demands of chronic mammal
toxicology testing.
I do not think that day is quite here yet.
Mr. BROWN. Would you consider a cosmetic product containing
such an ingredient safe?
Dr. KENNEDY. I would consider it as a strong presumption against its
safety.
Mr. BROWN. If a substitute ingredient could be found for this
ingredient-the ingredient that is found positive in the Ames test and
other short-term mutagenicity tests-which is negative in the Ames
test and other short-term mutagenicity tests, would you be more likely
to substitute this ingredient for the one which was positive in the
Ames test, absent other scientistfic data?
Dr. KENNEDY. Oh, yes. You mean, were I a formulator in the
industry?
Mr. BROWN. Yes.
Dr. KENNEDY. I would certainly do that, if for no other reason than
to make my product more secure against adverse regulatory action in
the future.
Mr. BROWN. Furthermore, if you knew that an ingredient in a
cosmetic product was found to be a carcinogen under the massive dose
animal experiments for carcinogenicity conducted by the National
Cancer Institute, and you knew that this ingredient might be absorbed
through the skin, would you consider the cosmetic products containing
this ingredient to be safe?
Dr. KENNEDY. No. I think one would have to make the strong
presumption in that case that they were unsafe.
The phrasing of your question that gave me a little pause, Mr.
Brown, was: "likely to penetrate the skin."
I think the issue of skin penetration is an important issue. I would
prefer that one be on somewhat firmer ground than "likely," but
certainly positive results in chronic carcinogenicity studies, and the
membership in a molecular family of things that are known to pene-
trate skin easily, would convince me that it ought to be gotten out of
the product.
Mr. BROWN. As the law currently stands, however, you feel you
would have to prove skin penetration before you take any action on
a product like this; is that right?
PAGENO="0389"
383
Dr. KENNEDY. I think that is a ~mattei of interpretation. I am
not certain about that.
Mr. BROWN. Yesterday, Dr. Corbett, a scientist for the cosmetic
industry stated that be personally favored premarket testing of
cosmetic products, and I underline "personally."
He stated, however, that be was opposed to making premarket
testing mandatory because it would mean that every time an in-
gredient in a product increased or decreased by perhaps 1 percent,
the industry would be forced to test the product over again before it
would be allowed to be put on the market.
Is this your conception of what a premarket testing program would
require?
Dr. KENNEDY. No. We are anxious to have some premarket testing
authority, but that does not mean that we will apply it to every small
change in formulation. I think that, like most statutory authorities,
we would be disposed to try to apply it sensibly~. It is like any other
resource allocation problem. We could not find all the time to read
all the safety test results that would result from every miniscule
change in a product formulation. That would be a poor way to use
our resources.
We would like to be able to require premarket safety substantiation
of important product ingredients. I would go further and say that
because I think interaction is important in cosmetics, that we might
want to be able to require safety tests of significant new combinations.
Mr. BROWN. Let me askyou a few questions about your present
statutory authority. Please tell me if you agree or disagree with the
following statements.
"As a practical matter, the FDA may react only after it discovers
an adulterated or misbranded cosmetic in the marketplace."
Dr. KENNEDY. I am a little unclear, Mr. Brown, about what you
are expecting here. You want my reaction?
Mr. BROWN. Do you believe that this is generally the case under
the current authority?
Dr. KENNEDY. I am anxoius not to give too much away here. I find
our authority is infirm and deficient in this regard, but there is a good
deal that we can accomplish by regulation.
I would say that there is less clarity in our ability than we would
like, but that some can be accomplished by regulation.
Mr. BROWN. But the fact is you need to first prove that the product
may be adulterated or misbranded; is that right?
Dr. KENNEDY. You are right about the burden.
Mr. COOPER. We would have to satisfy a court that the product is
either adulterated or misbranded. However, we might ease that
burden somewhat in advance by going through a rulemaking proceed-
ing in which we established our position with respect to, let us say,
ingredients that might constitute adulterants.
We would go into court relying on a regulation rather than having
to make an individual factual case.
But ultimately we would have to be in court.
Mr. BROWN. Another statement I would like you to react to is this:
"Under the current statutory scheme, the FDA cannot require that
the manufacturers test for safety prior to marketing the product."
Dr. KENNEDY. I think you already have my reaction to that. We
would like the authority to require that, where we think it is necessary.
PAGENO="0390"
384
Mr. BROWN. Another statement is this: "The cosmetic producers do
not violate the act if they fail to conduct a single safety test, either
before or after introducing a new product."
Dr~ KENNEDY. Again, we would like the authority to require that.
Mr. BROWN. "FDA has no authority to require that the companies
provide necessary information that would enable the agency to con-
duct its own premarket review."
Would you react to that?
Dr. KENNEDY. Yes; as a part of any premarket review, we would
require access to the data in order to conduct our own evaluation.
Mr. BROWN. "Manufacturers cannot be compelled to submit in-
gredient lists, consumer complaints, or test data."
Dr. KENNEDY. That is true. We wish it were not.
Mr. BROWN. "Cosmetic companies are not required to inform the
FDA that they, or their products, exist."
Dr. KENNEDY. That is correct also. Again, as I said in my state-
ment, we would like to have registration authority.
Mr. BROWN. Dr. Kennedy, your answers seem to indicate that in
the area of cosmetic regulation, the power to regulate, or at least
much of the power to regulate, belongs to each individual cosmetic
company, and that the standard for what is safe is determined and
controlled by those individual companies.
Dr. KENNEDY. In the absence of a specific statutory mandate to
require test data and plant and product registration, and to do in-
spections, one relies, out of necessity, on programs that are essentially
voluntary.
So, I think your description is right. You 11 ave heard correctly
from the GAO that our success in obtaining those data voluntarily
has not been as good as we would like.
Mr. BROWN. Thank you, Mr. Chairman.
Mr. WALGREN [presiding]. Commssioner, when you say that you
would like to have registration authority, has the FDA ever asked
the Congress to provide that authority?
Dr. KENNEDY. Yes; we have. Unless I am very much mistaken,
I believe that all, of at least most, of the features that we have de-
scribed as being important but missing were parts of the bills in-
troduced last year and in previous years on the Senate side. In our
comments on legislation in previous Congresses we came out in favor
of every one of those provisions. There was a bill by Congressman
Paul G. Rogers on the House side that also had all of those provisions
in it.
So, we are on record repeatedly in this area, that is, of being in
favor of those provisions.
Mr. WALGREN. So we could translate your statement that you
would like to have that authority to mean that you believe you need
that authority and that you would like to see legislation which would
provide that authority?
Dr. KENNEDY. Yes.
Mr. WALGREN. Would the administration support a bill to that
effect?
Dr. KENNEDY. The previous administration supported our position
and I have every reason to believe that it would be warmly supported
again.
PAGENO="0391"
385
Mr. WALOREN. That would include registration authority or the
authority to require anyone producing a cosmetic to at least let the
officials in the Government who are concerned about chemical safety
know that they are operating in* the area and it1 would include the
requirement to disclose the ingredients of products which they
put on the commercial market, I suppose.
But what about requiring at least the report of harmful effects
that they may receive?
Dr. KENNEDY. Yes ;~ we have asked that adverse reaction reporting
be make, that is, for us to have the authority to require adverse
reaction reporting as well.
Mr. WALGREN. And that would be mandatory?
Dr. KENNEDY. Yes. We would make it mandatory.
Mr. WALGREN. Do you feel that the public responsibility could be
discharged effectively without that authority?
Dr. KENNEDY. It is very much more difficult-some of it cannot
be discharged at all. This gets me into a comment on the GAO's
earlier testimony-I think they are correct in saying that the FDA
has not, in the past, fully used its existing regulatory authority, that
is, the existing statutory authority to pursue these matters as inten-
sively as one might desire.
But, I would like to add to the reasons that the GAO witnesses
gave you a much more important one in our view. If you have a
a variety of important public health protection responsibilities under
your act-and I ask you to recall that our responsibilities over drug
safety and over food safety are perhaps even more compelling than
our responsibilities over cosmetic safety-that is, if you have three
different portions of your act, and under two of them you have
relatively clear statutory authority, and under the third you have
relatively unclear authority, then only a silly manager overinvests
in the area where the authority is weak because his resources get
chewed up for very little outcome.
Mr. WALGREN. I would like to understand a little bit more where
we are in the knowledge of skin absorption and what have been our
efforts recently.
Commissioner Kennedy ~ays that we are conducting laboratory
studies on skin penetration on NDELA.
How large an effort is that? What kind of tests are being run, and
is the state of our knowledge changing?
Dr. KENNEDY. I think it is a little too soon to say that the state
of our knowledge is changing. After all, this is a recent prog.ram.
Remember, the data reported by Dr. Fine are substantially less than
a year ~1d, and from a dead standing stop we had to work up both
an analytical capability for NDELA and assign the personnel and equip-
ment to mount the effort and move it forward. We also had to put in
place the skin penetration studies that form the second part of that
research.
Dr. Roberts may be able to tell us something about the extent of
resources or Dr. Scheuplein may.
Dr. ROBERTS. As part of the Division of Toxicity in the Bureau
of Foods, there is a Dermal and Ocular Toxicity. Branch. We have,
at the present time, five people. Two of those peopla are now working
on skin penetration of NDELA.
PAGENO="0392"
386
This study began about a month ago as a continuation of a prior
study of about 6 months ago that had to be suspended when one of
our people was transferred.
We expect that the results of this skin penetration study will be
ready within a month.
Mr. WALGREN. How long has that study been going on?
Dr. ROBERTS. The present study with the personnel we have on
hand has been going on just about 1 month. It is a continuation of
an earlier one that had to be suspended because of the fact that the
person we had for the study was transferred.
Mr. WALGREN. So you have one man full time for 2 months in this
effort at this point?
Dr. ROBERTS. That is right.
Mr. WALGREN. And, you have five people involved in some way in
skin penetration or only two of those were involved in skin penetration?
Dr. ROBERTS. 0niy two of those. We have five people for the whole
Dermal and Ocular Toxicity Branch.
Mr. WALGEEN. Five people for the whole Branch?
Dr. KENNEDY. The Dermal and Ocular Toxicity Branch of the
Toxicity Division is what we are talking about. I assume you are
talking about professionals in that number. Is that right?
Dr. ROBERTS. No.
Dr. KENNEDY. No. Then that is total people.
Mr. WALGREN. Total people?
Dr. KENNEDY. Yes.
Mr. WALGREN. So, of the five, perhaps only three are actually work-
ing on the products and the others may be staff support; is that right?
Dr. ROBERTS. Right.
Mr. WALGREN. The industry that we are trying to deal with is a
$9 billion industry.
Dr. KENNEDY. Yes; I think that is correct.
I might insert here, Mr. Walgren, that it is quite characteristic of
the Food and Drug Administration that not all of its research is per-
formed in-house; that is, it would be typical of most parts of the
Bureau of Drugs or the Bureau of Foods that if we had a problem of
this sort that we needed to get solved, rather than taking on extra
personnel or redirecting existing research personnel from other efforts
that might be equally important, we would attempt to find sources of
contract help outside.
In this particular case, the newness of the information that has
raised these concerns has made it necessary to do it by internal re-
allocation of what you have just heard is a rather thin resource. We
probably will be supporting, through grant and contract mechanisms,
some outside work as well.
Mr. WALGREN. Where did the estimate of the 40 pounds per year
come from?
Dr. ROBERTS. That is a projected estimate based on the retail sales
of toiletries, cosmetics, and soaps. It turns out that, based on such,
an estimate, one can estimate that about 3.7 million pounds of soaps
toiletries, and cosmetics will be sold in 1978.
If you divide that number by an estimated target population of
either 200 million or 100 million or what have you, you can see that
the estimated use per person is roughly from 10 to 40 pounds per year.
PAGENO="0393"
a87
Dr. WALGREN. Is there any relationship between physical applica-
tion and absorption rates, or are we talking about the absorption and
skin penetration of really molecular-level chemicals?
Dr. ROBERTS. I am not sure I really understand that question.
Dr. KENNEDY. I think, Mr. Walgren, you are really asking what
kinds of skin penetration figures we are really dealing with, are you
not? I mean, how much of any particular molecular species is likely to
go through the skin.
That varies terribly widely. There are some compounds that are
just very insoluble in the kinds of material of which animal skin and
human skin is made that go through or penetrate very poorly.
So even a very thinly applied dose, even on a relatively permeable
part of the skin, like the scalp, of only a few thousandths of a percent
might go through.
On the other hand, there are some compounds that are quite per-
meable and that pass through the skin readily.
Unfortunately, the so-called coal-tar hair. dyes are among the more
permeable compounds that we know of. The figures that various re-
search groups have been able to produce for penetration of those dyes
vary a little bit, but they are running around 1, 2, or 3 percent. In
some experiments, they are substantially more.
So it is possible in fact, at least in some animal species and perhaps
in humans, that with repeated application to the skin of these com-
pounds, one could reach blood concentrations of the same order as
one could reach by feeding the animals.
Mr. WALGREN. The reason this interests me is that we are under
such criticism for getting the Government involved in the areas they
should not be involved in. It does not seem obvious to the public that
we should be involved in these, that is.
I think, in general, for someone who has never thought about the
subject before, cosmetics are not usually thought of as being ab-
sorbed into the system.
Therefore, that is a new, and, I think, very essential idea for the
public at large anyway.
What you are saying is that our knowledge has not particularly
changed in that area. So, I am wondering if we are thinking of moving
into this area, that in order to set a basic or to make it accepta4ble to
the public to put even 2 months of man-hours work on it, whether or
not we should be emphasizing skin absorption and perhaps being able
to demonstrate exactly what is going on to the layman.
Without that, I see a great resistance from the public to taking this
seriously.
Dr. KENNEDY. I think that is true. I know the feeling of being
accused of getting involved in areas that people would rather not see
a regulatory agency get involved in. I agree with you that it is very im-
portant that we try to get some public understanding for the serious-
ness of these problems.
I would like to emphasize, though, that dermal toxicity is not a new
phenomenon, although it is not often considered in terms of cosmetics.
Many of the more damaging pesticide exposures, for example, in
farmworkers and others, are dermal exposures. The Occupational
Safety and llealth Administration worries about dermal exposure in
connection with a great many workplace toxic substances hazards.
PAGENO="0394"
388
I hope you will help us with this, but I think what we need is a more
concerted Government-wide effort on all aspects of toxic chemicals
hazards. We need more work on inhalation toxicology and on dermal
toxicology. We need a better national epidemiological system.
The Food and Drug Administration is responsible for only a small
piece of this. But I think that many other agencies would also tell
you that they have relatively small resource commitments to these
kinds of problems.
One of the things that I hope will come out of our four agency al-
liance is significantly more cross-Federal attention to these sorts of
problems. I am grateful for the opportunity to say so.
Mr. WALGREN. Well, we certainly cannot be accused of having put
very much Federal effort into skin penetration at this point, if that is
the degree of specific focus research that we have done on that; is that
correct?
Dr. KENNEDY. I would not want to confuse you. You have heard
about a specific project dealing with the skin penetration of a particular
product or a compound of newly generated concern.
That does not represent the total number of scientist-years that
FDA normally puts into all issues of skin penetration. Although I can
tell you that would not sound very large either.
Mr. WALGREN. Mr. Maguire?
Mr. MAGUIRE. Dr. Kennedy, I asked Mr. Ahart earlier about
FDA's failure to use, in the past, its existing authority. He said there
was not enough pressure, and he said there was a lack of resources.
I would like you to answer the same question. Why has FDA not
been using its authority, in your judgment?
Dr. KENNEDY. I think the reasons that Mr. Ahart mentioned are
probably reasons that have played some role.
I would like to be able to sit here and tell you, Mr. Maguire, that
the Food and Drug Administration never allocates its resources accord-
ing to pressure. But you and I both know that would be foolish.
Mr. MAGUIRE. That was going to be a followup question.
Dr. KENNEDY. So, obviously, there is public pressure. Bringing to
our attention problems-by the public, by the Congress and by sci-
entists who perform outside of the Agency-is an important allocation
pressure.
But, as I said in response to an earlier question to Mr. Walgren, I
think the more important reason is that if you have important public
health responsibilities in three different areas, and if each of them lays
compelling claims to your resources, and in one of those areas you have
manifestly inadequate statutory authority, and in the other two it is
at least better, then a wise man is going to allocate more heavily to
where he is going to get a return.
Mr. MAGUIRE. You have been quite critical today of the existing
1 aw in your statement. At the conclusion of your statement you made
a number of recommendations for improvements.
Is the administration prepared to submit to this Congress proposed
legislation to protect people more adequately against cancer-causing
substances in cosmetics or other toxic substances in cosmetics?
Dr. KENNEDY. Yes, Mr. Maguire, I think we are prepared to par-
ticipate with committees of the Congress and Members of the Congress
in drafting and designing legislation.
PAGENO="0395"
389
Mr. MAGTJIRE. Will you actually make a proposal, or has that not
yet been decided?
Dr. KENNEDY. I do not think that has yet been decided. As you
know, there has been, in recent Congresses, activity on the House and
Senate side with regard to new cosmetics legislation.
FDA has supported it. The Department of Health, Education, and
Welfare has supported it. As a department, we have supported the
kinds of provisions that we have discussed.
So, the sorts of proposals we would make are out there and are
clear enough.
Mr. MAGUIRE. I do not think they really are. The~e is nothing
quite as clear as submitting your own piece of legislation which really
does provide an impetus which otherwise is absent.
Mr. Eagleton, for example, for some time has had a varitey of rec~-
ommendations. But we need the impetus that your leadership would
provide, or at least your endorsement of a specific set of recommen-
dations that are more detailed than what we have had from you today.
Dr. KENNEDY. We would be delighted to do that. We have endorsed
very specific recommendations in the past.
I am not prepared to tell you here and now this morning, not having
been asked the question before, whether there will be an administra-
tion cosmetics bill. But I am certainly prepared to tell you that I
think my colleagues in the department and I are prepared to suppc~rt
the sorts of provisions that we have discussed and to help you to work
it into language that will be agreeable to all of us, or at least almost
all of us, and to work with you to support it.
Mr. MAGUIRE. Excellent. Thank you.
With respect to the 100 ingredients in the CTFA dictionary which
we have here [indicating], it has 100 things that NIOSH has said
are suspect, or that they are known carcinogens.
What are you doing about that list now, if anything?
Dr. KENNEDY. A number of the compounds on that list, and a
number of the ingredientscited from the GAQ "drugstore" that we
had here this morning on the table, are compounds that are now under
test. I hope we will know fairly soon something about their status
that says more th'an "suspect."
Even the more robust provisions of the other part~ of the Federal
Food, Drug, and Cosmetic Act do not allow us tQ hoist a compound
from the marketplace on the basis of suspicion of ~arcinogenesis.
Mr. MAGUIRE. But we have products on the shelves right now
which are purchased by tens of millions of people. across this country.
We have Grecian Formula shampoo, and Kindness hair conditioner,
et cetera.
I know that people are concerned. ..
So the question i~ this. What will you do and how quickly will you
do it? .
Dr. KENNEDY. We will undertake product removals and undertake
the addition of warning statements as promptly as we can, following
the submission of data and following the development of data that
constitute clear enough proof of carcinogenicity or other forms of
toxicity where we have a reasonable chance of defending that regula-
tory action in the courts. .~ .
PAGENO="0396"
390
Mr. MAGUIRE. But FDA is going to have to develop that data; is
that right?
Dr. KENNEDY. We cannot develop all of it. We do not have facilities
for long-term chronic toxicity testing that would allow us to investi-
gate even a tiny fraction of the compounds on the NIOSH suspect list.
The National Cancer Institute, and the Department, through con-
tract, have had, and are having, some of them tested.
But I have to say that it will be some time before we get around to
testing all of the possibly hazardous substances that are now in
cosmetics. It!will be sometime even before we get around to testing
all of the possibly hazardous substances that are in foods.
Mr. MAGUIRE. Do you believe that the animal feeding studies con-
ducted at the National Cancer Institute are a sufficient scientific basis
on which to act?
Dr. KENNEDY. I would rather not make a blanket statement about
that, Mr. Maguire, but the ones that we have reviewed and that we
have begun action on, like the one on 2,4-diaminoanisole, we certainly
regard as adequate. I am not eliminating the possibility that an NCI-
funded contract study, for example, might not come in with a defect.
Mr. MAGUIRE. My question really goes to the question of whether
the feeding studies of animals are, in your judgment, a legitimate
scientific basis on which to make a regulatory decision. There has been
a lot of discussion about that in these and other hearings.
Dr. KENNEDY. If I did not believe that, I would be back in California
teaching biology.
Mr. MAGUIRE. Thank you.
Mr. WALGREN. I gather that until that time that we and the Ameri-
can public will continue to rely on the guarantees that we already
have as displayed on the Kindness Shampoo package, which is: "If
product or performance defective Good Housekeeping guarantees re-
placement or refund to consumer."
Mr. Wunder?
Mr. WUNDER. Thank you, Mr. Chairman.
Dr. Kennedy, the FDA has had regulatory authority, albeit not what
you think appropriate and necessary, for 40 years. Is that true?
Dr. KENNEDY. Regulatory authority for what?
Mr. WUNDER. Over cosmetics.
Dr. KENNEDY. Yes, some regulatory authority.
Mr. WUNDER. Yes.
I assume that FDA has kept up with the literature and what is
going on in the cosmetics industry, to some degree; is that right?
Would that be a fair statement?
Dr. KENNEDY. Yes.
Mr. WUNDER. Let me ask you this. This goes to the public alarm
issue.
Do you know of any studies where birth defects have been linked
to the use of these cosmetics?
Dr. KENNEDY. Do you mean birth defects-
Mr. WUNDER. In humau beings.
Dr. KENNEDY. Linked epidemiologically to the use of cosmetics?
Mr. WUNDER. In any respect.
Dr. KENNEDY. I do not know of any offhand, but I will ask my
colleagues for help. Until a few months ago this was not literature
that I tracked terribly carefully.
PAGENO="0397"
391
There are ingredients, some ingredients in cosmetics that I think
look to be teratogenic in animal studies, but that is not the question
that you asked.
Mr. WUNDER. So there are none; is that the answer?
Dr. KENNEDY. None known to me.
Mr. WUNDER. None known to anybody on the panel?
Dr. KENNEDY. That is correct.
Mr. WUNDER. Are there any studies linking the use of cosmetics
with cancer in human beings?
Dr. KENNEDY. Well, that depends on which side you take in the
interpretation of the epidemiological studies done on beauticians,
cosmetologists, and users of beauty shop products.
My own view of the matter is that it is not possible to decide yet,
but there are people who believe that they are indicative.
Mr. WUNDER. Let us take any of the diseases known to modern
man. Is there any study linking any disease with the use of cosmetic
products? Let us leave out cancer for the moment.
Dr. KENNEDY. Yes. There are some eye infections. There are
certainly skin irritations and sensitation problems that have been
associated-
Mr. WUNDER. Aside from those.
The 1938 act-it was the eye situation that brought that about.
Dr. KENNEDY. Yes.
Mr. WUNDER. They knew about the irritation problem in 1938
because that was discussed in the hearings then.
But other than those, what about it?
Dr. KENNEDY. We did ban vinyl chloride in cosmetics in occupa-
tional studies, but that was a propellant. Perhaps that is not respon-
sive.
Mr. WUNDER. You were asked a question by Mr. Brown about the
Ames test. The question was this:
If there was an ingredient, a compound, that failed the Ames test, but there was
a substitute that passed the Ames test, would you use the substitute?
You said: "Yes."
Dr. KENNEDY. Yes.
Mr. WUNDER. The question that was asked of Dr. Corbett yesterday
about the Ames test was along these lines, along these similar lines,
but his answer was-and I would like to get your reaction to it:
If there was a compound that we had used for maby years and it failed the
Ames test, but we otherwise had a track record of safety, then I would not go to
some new compound without any track record of safety.
What is your reaction to that statement? That was the thrust of
Dr. Corbett's testimony.
Dr. I~ENNEDY. I understand.
It all depends on what you mean by "track record." There are a lot
of compounds that have been out there in the marketplace which
most people are prepared to say are safe because they have not yet
been able to affiliate the use of that compound with any health
problem.
But, in fact, as we know, even for devastatingly dangerous com-
pounds that affiliation can be subtle and difficult to perceive. After
all, in the ~94O's everyone thought that tobacco was safe. Everyone
PAGENO="0398"
392
would have asserted very stoutly, as the tobacco industry did, that
there was no problem with it.
So, if by "track record" you mean the general public perception
that people are not keeling over and dying, I guess I have to tell you
I am not very reassured by that.
Mr. WUNDER. I see.
The thrust of it was along these lines. If you had some evidence,
and then you go into something that you do not know anything about,
that is, if those were the options, and if that was the concern of Dr.
Corbett, that is, that you do not know anything about this one because
it has not been tested-
Mr. MAGUIRE. If the gentleman will yield, I think it is also important
to recognize that we are talking about the Ames test and we are talking
about a test which can be conducted in a matter of days. I do believe
that Dr. Corbett also said that if he had a negative result, that is, a
result that showed that there was no tumorigenic activity or muta-
genic activity in this case, excuse me, and another ingredient which
showed that there was, then he would take the one where there was not.
So, given that we are talking about the Ames test, and the period
of time that we are talking about, and in getting results on any sub-
stance which we might want to look at, is indeed a very short period
of time.
Mr. WTJNDER. According to my recollection, those were cases where
you had two new products and one passed and one failed.
I have no further questions, Mr. Chairman. Thank you very much.
Mr. WALGREN. The Chair will recognize Mr. Brown.
Mr. BROWN. Dr. Kennedy, I have a few more questions.
These specifically relate to the actions you are about to take to
place a warning label on hair dyes containing 4-methoxy-m-phenyl-
enediamine.
Last week, the Cosmetic, Toiletry, and Fragrance Association
asserted that FDA was basing its action on only one test.
Can you react to that statement?
Dr. KENNEDY. I think that there are results on two species in that
case, so I do not know really where that comes from.
Let me hasten to say that I do not think you have to have two.
Mr. BROWN. But aren't we really talking about a whole range of
tests. Did not FDA consider other types of testing in making its
decision? I am talking about tests besides carcinogenicity tests.
Dr. KENNEDY. We certainly looked at a range of data.
I thought what you were asking for was this. Which of the chronic
toxicology studies do you consider critical?
Obviously, we look at everything, including several different skin
penetration experiments, some of which are better than others.
Mr. BROWN. Just as a final question, Dr. Kennedy, if you were in
the position where you were considering dying your hair, with the
knowledge, that you now have, concerning the possible risk involved,
would you use a coal tar hair dye?
Dr. KENNEDY. I am grateful that this subcommittee always gives
me an opportunity-I am unmotivated in that direction, Mr. Brown.
I do not think it would do a thing for me.
But even if it did, I think I would give it a miss.
PAGENO="0399"
393,
Mr. WALGEEN. Dr. Kennedy, I think you should know that accord-
ing to whoever makes this Grecian Formula, you are "foregoing the
social and business advantages and the personal satisfaction that
comes with the more youthful look."
Dr. KENNEDY. I knew that before I started turning gray, Mr.
Walgren.
Mr. WALGEEN. Well, we appreciate your testimony, and we want
to thank all of the witnesses who came to the hearing today.
Although we make light of this in some ways, it does not have a
thing to do with the seriousness of the problem.
Thank you very much.
The hearing is adjourned.
[Whereupon, at 11:55 a.m., the hearing adjourned.J
PAGENO="0400"
PAGENO="0401"
CHART 1
k
List of Chemicals in Bioassay Program That Are
Hair Dye Ingredients
C,,
CHEMICAL NAME
~
DATE
"ON"
TEST
DATE
"OFF"
TEST
DATE
FINAL REPORT
PROMISED TO
LABOR-HEW
SUBCOMMITTEE
DATE
FINAL REPORT
PROMISED TO
OVERSIGHT AND
iNVESTIGATIONS
SUBCOMMITTEE
DRAFT REPORT
AVAILABLE
(TECHNICAL
REPORT)
(DATE)
FINAL REPORT
AVAILABLE
(DATE)
1, 3-Phenylenediamine
1/70
1/12
12/77
3178
-
-
1, 4-Phenylenediamine
2/73
5176
12/77
5/78
-
-
2, 5-Toluenediamine
3/72
2/75
7/77
10/77
7/77
-
0-Anisidine
3/74
3/76
2/78
5/78
-
-
4-Chloro-1, Z~PhenyIenediamine
3/73
4/75
6/77
9/77
12/77
-
1-2-Phenylenediarnine
6/70
6/72
12177
3178
-
-
P-Anisidine Hydrochloride
3/74
3/76
1/78
4/78
12/77
-
4-Amino-2 Nitrophenol
3/74
3/76
10/77
4/78
-
-
2, 4-Biaminoanisole Sulfate
4/72
3/75
11/77
2/78
12/77
-
4-Nitro-P-Phenylenediamine
6/72
8/74
6/77
3/78
-
-
2, 4-Tohienediamine
1-Phenyl-3-Methyl-5-Pyrazolone
10/73
2/76
3/78
12/77
12/78
-
-
10/73
12/75.
6/78
-
-
N-Phenyl-1, 4-Phenylenediamine
2/73
12/74
8/77
4/78
-
-
Sources: National Cancer Institute testimony before labor-HEW Subcommittee, Committee on Appropriations, U.S. House of Representatives,
95th Congress, 1st Session, March 7, 1977.
Letter from Or, Gay Newell, Acting Director, National Cancer Institute to Committee on Interstate and Foreign Commerce, U.S.
House of Representatives, Subcommittee on Oversight and Investigations, July 7, 1977.
Jan. 16, 1978
PAGENO="0402"
CHART 2
Selected Examples of Chemicals Listed
in the Bioassay Program
DATE
DRAFT
DATE
FINAL REPORT
REPORT
FINAL REPORT
PROMISED TO
AVAILABLE
FINAL
DATE
DATE
PROMISEDTO
OVERSIGHTAND
(TECHNICAL
REPORT
CHEMICAL NAME
USE
"ON"
TEST
"OFF"
TEST
LABOR-HEW
SUBCOMMITTEE
INVESTIGATIONS
SUBCOMMITTEE
REPORT)
(DATE)
AVAILABLE
(DATE)
Acenaphthene, 5-Nitro-
Chemical intermediate or
catalyst
1/73
12/75
8/77
11/77
-
-
Ethane, 1, 1-Dichloro
Solvents
4/72
5/74
5/71
10/77
5/77
-
Daconil
DaunOmycin
Pesticide
2/72
4/69
6/74
8/71
6/77
1/78
9/77
4/78
6/77
-
-
-
Pharmaceuticals/biologicals
Diphefl~tamine, 4-Nitroso-
Miscellaneous categories
7/12
9/74
9/71
12/77
-
-
Hydrazine, 1, 1-Diphenyl-
Chemical reagent
4/72
3/75
8/77
11/77
-
-
Lead Acetate
Dye or dye manufacture
8/12
9/74
3/78
6/78
-
-
Tryptophan, 1-
Vinbiastine
Food or food additives
2/73
5/69
2/75
5/71
11/77
1/78
2/78
4/78
-
-
-
-
Pharmaceuticals/biologicals
Acetic Acid, Nitrilotri
Other
2/73
2/75
4/77
3/77
-
4/77
Dapsone
Malathion
Phenol
Pharmaceuticals/biologicals
5/72
12/71
10/75
5/74
4/74
2/79
8/77
6/77
2/80
10/77
10177
2/80
8/77
6/77
-
1/78
-
-
Pesticide
Pharmaceuticals/biologicals
Sources: National Cancer Institute testimony before Labor-HEW Subcommittee, Committee on Appropriations. U.S. House of Representatives,
95th Congress. 1st Session, March 7,1971,
Letter from Dr. Guy Newell, Acting Director, National Cancer Institute to Committee on Interstate and Foreign Commerce, U.S.
House of Representatives, Subcommittee on Oversight and Investigations, July 1, 1977.
Jan. 16, 1978
PAGENO="0403"
APPENDIX B
written on request of the
Federal Trade Comi ssion
UNIVERSITY OF CALIFORNIA, BERKELEY
BERKELEY~ DAVIS IRVINE LOS ANGELES `RIVERSIDE' SAN DIEGO SAN FRANCISCO SANTA BABBASA `SANTA CIWZ
DEPARTMENT OF BIOCHEMISTRY BERKELEY, CALIFORNIA 94720
February 17, 1978
AFFIDAVIT OF DR. BRUCE N. AMES
CONCERNING HAIR DYE CHEMICALS
I, Dr. Bruce N. Ames, being duly sworn, do hereby state my reasons for
believing that the use of hair dyes containing the chemicals listed below*
poses a significant risk to consumers. The risk amply justifies requiring
a warning to users in advertising and labeling.
I am a Professor of Biochemistry at the University of California at
Berkeley, and have worked for 15 years in the area of chemicals which cause
cancer and mutations. I am a member of the National Academy of Sciences and
was appointed by President Ford to the National Cancer Advisory Board (the
Board of Directors of the National Cancer Institute). I enclose a C.V.
(Appendix 1).
I believe the six listed chemicals pose a risk to humans for the
following reasons:
1. The chemicals are~mutagens. That is, they belong to a small group
of chemicals which damage DNA, the genetic material. They have the potential.
therefore, to cause birth defects and long-term genetic damage. For this
reason, pregnant women should be especially cautious about using such products.
All of the listed chemicals were mutagenic when tested in the
Salmonella (Ames) Test (Appendix 2). Subsequently, they have been found to
be mutagenic when tested in a variety of other test systems, inc1udin~
Drosophila (fruitflies), and cultured human or other mammalian cells. A
review of the current status of these tests is presented for each chemical
in Appendix 3.
Most, if not all, chemicals which are mutagens are also carcinogens.
The ability of the Salmonella test to predict carcinogenicity has been
extensively analyzed~iiing several hundred chemicals with known cancer~
causing properties. The test achieved a high degree of accuracy and did
particularly well with carcinogenic aromatic amines similar in structure to
numerous hair dye chemicals.
(397)
PAGENO="0404"
398
Affidavit/Bruce N. Ames - 2 - February 17, 1978
The excellent agreement between the Sa1monell~ mutagenicity results
and the other test systems establishes these chemicals as mutagens. The
industry has tested many of the hair dye chemicals in the dominant lethal
test and reported negative results~. This test, however, is well known to
miss many important classes of carcinogens and, in particular, has not been
validated for the class of aromatic amines, which includes the hair dye
Ingredients and such well known human carcinogens as ~-naphthy1amine and
benzidine.
2. The chemicals are carcinogens it~ animals. The National Cancer
Institute has indicated that the listed chemicals have been shown to cause
cancer in rodents in tests being completed by the National Cancer Institute.
These tests further support the relevance of results in the short-term tests
to potential hazards of hair dyes.
3. There is a risk to humans. Hair dye chemicals have been shown to
penetrate the scalp in sigilificant quantities. This, together with the high
correlation between human and animal carcinogens, suggests a definite risk to
those using hair dyes containing the listed chemicals. In evaluating this
risk, it is important to consider that the development of human cancers will
lag twenty years or more behind the initial exposure. Since hair dye use has
increased over recent decades, it is quite possible that any human effects of
hair dye use will be increasingly evident in the future. Furthermore, since
the chemicals are also all mutagens, they may pose a risk of birth
defects and possibly genetic damage to future generations.
Bruce N. Ames
Professor of Biochemistry
BNA/ssk
* 2,4-diaminoanisole
2-nitro-p-phenylenediamine
4-amino-2-ni trophenol
p-phenylenediamine
Direct Black #38
o-phenylenediamine (possibly no longer used)
Appendix 1: C.V. of Dr. Ames
Appendix 2: Ames et al., Hair Dyes are Mutagenic
Appendix 3: GQ1d i~iW~mes, Hair Dye Components: Review of Mutagenicity
Appendix 4: Interview with Lester Brown
PAGENO="0405"
399
27 January 1978
revised: 15 February 1978
Testimony for House of Representatives
Oversight Committee Hearing on Cosmetics
Hair Dye Components: Review of Mutagenicity
and Other Short4erm Tests
Cheryl Gold and Bruce N. Ames
Depa~~tment of Biochemistry
University of California
Berkeley, California 94720
PAGENO="0406"
400
SUMMARY
In 1975, Ames, Kammen and Yamasaki found the following 11 hair dye
chemicals were mutagenic in Salmonella: 2,4-diaminoanisole, 2,4-diamino-
toluene (dropped from use because of carcinogenicity), rn-phenylenediamine,
2,5-diaminoanisole, 2,5-diaminotoluene, p-phenylenediamine (after mixing
with peroxide), 2-nitro-p-phenylenediamine, 4-nitro-o-phenylenediamine,
o-phenylenediamine, 2-amino-5-nitrophenol, and 2-amino-4-nitrophenol. In
addition, 4-amino-2-nitrophenol has since been shown to be a mutagen in
the Salmonella (Ames) test, as have Disperse Blue #1 and Direct Black #38.
So far, 7 of these compounds, 2,4-diaminoanisole, 2,4-diaminotoluene, 2-nitro-
p-phenylenediamine, 4-nitro-o-phenylenediamine, m-phenylenediamine, p-phenylene-
diamine, and 2,5-diaminoanisole, have been tested and found to be active in
other short-term tests. To this date, six of these chemicals, 2,4-diamino-
anisole, 2-nitro-p-phenylenediamine, 4-amino-2-nitrophenol, o-phenylenediamine,
p-phenylenediamine, and Direct Black #38, appear to be carcinogens in NCI
animal tests. In addition, three other hair dye related ingredients,
o-anisidine, 4-chloro-o-phenylenediamifle, and Direct Blue #6, appear to be
carcinogens in the NCI animal tests: the first two are mutagens, and the
latter hasn't been tested but is similar in structure to the known mutagens
Pontacyl Sky Blue 4BX and Direct Black #38.
Three chemicals which are not mutagenic in Salmonella, N-phenyl-p-
phenylenediamine, l-phenyl-3-methyl-pYraZOlOne, and resorcinol, do not appear
to be carcinogens in the NCI animal tests.
PAGENO="0407"
401
Many of the following hair dye ingredients are under study by the
National Cancer Institute. In addition to cancer tests, many of the
compounds have been tested in a number of short-term tests, such as
mutagenicity using our Salmonella/liver test, gene mutation using mouse
lymphoma cells, chromosome damage and morphological transformatio~1 in
mammalian cells, mutagenicity in Drosophila, and sister chromatid exchange.
These chemicals will be presented first.
An NCI index number is given, and CAS numbers may also be included.
Full citations for references are listed in the appendix.
The list which follows this compendium contains all other hair dye
chemicals under study by the National Cancer Institute.
PAGENO="0408"
402
OCH3
2,4-diaminoanisole NH2
(4-methoxy-m-phenylenediamine = 4MMPD)
[also sulfate salt = 4MMPDS]
CANCER TEST (NCI# = C01989, sulfate) REFERENCES
(CAS# 615-05-4, sulfate)
positive 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) very strong mutagen 1,4,20
(TA1538 +S9: 4000 revertants/50 ig [1])
Drosophila mutagen 3
Mouse lymphoma questionable response, however 15
activation was not used; author
believes test will not be
definitive until activation
is used
Reference to use in hair dyes
PAGENO="0409"
CANCER TE~I~ (NCI# = C02302, C01832 [sulfate])
(CAS# = 95~80~7)
positive (preliminary result of Nd)
positive (rat sarcomas)
positive (rat liver carcinomas)
__ RESULTS
__________________ mutagen
(TA1538 1-59: 270 revertants/100 ~g [1])
___________ mutagen
______________ morphological transformatlQns
observed
Note: This compound was formerly used in hair dyes but was taken off the
niarket when it was found to cause cancer In animals.
403
m-tol uenedi amine
(2 ,4-di ami notol uene)
[also sulfate salt]
SHORT TERM TESTS
Salnonel la (Anies~
Drosop~~j,i~
~ hamster
cells
14
21
8
1 ,20
3,5
17
24.600 0 78 27
PAGENO="0410"
404
NH2 `HCl
m-phenyl enedi amine' 2HC1
0
NH2 HC1
CANCER TEST* REFERENCES
test has been completed; results appear negative 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) mutagen 1,20
(TA1538 +S9: 330 revertants/lO0 ~ig [1])
Mouse lymphoma mutagen 11,15
Reference to use in hair dyes
* Note: m-phenylenediamine is listed as NCI Compound 24 in NCI Technical
Reports, September 1976
PAGENO="0411"
2,5-diaminoanisole
CANCER TEST
not under test by MCI
405
REFE~ENCE~
SHORT TERM TESTS
Salmonella (Ames)
E~cherichia coil
i,2o
13
RESULTS
mutagen
mutagen
Reference to use in hair dyes
PAGENO="0412"
406
test has been completed; final results have not been determined
RESULTS
__________________ weak mutagen
(TA1538 +S9: 40 revertants/lOO iig [1])
2,5.~toluenedlamine SO~
CANCER TEST (NCI # C01832)
(CAS # = 6369-59-1)
REFERENCES
14
However, upon treatment of the chemical
with peroxide, there is a 40-fold
increase in mutagenicity
SHORT TERM TESTS
Salmo~ie11a (Ames)
OTHER TESTS
Terato~eni city
in mice
1 ,2O
RESULTS
teratogen
26
Reference to use in hair dyes
PAGENO="0413"
407
NR2 RC1
p-phenylenediamine'HCl
(1,4-phenylenedlamine)
N}~ `HCl
CANCER TEST (NCI# = C03930) RE~ERENc~
positive in rats 18
positive (preliminary result of Nd) 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) very strong mutagen after addition of 1,20
peroxide
(TA1538 +S9: 2400 revertants/20 ug Cl])
~ros~h la mutagen . 3
Reference to use in hair dyes
PAGENO="0414"
408
2~ni tro-p~phenyl enedi amine
(2-nitro-l ,4-phenylenediamine)
CANCER TEST (NCI# = C02222)
(CAS# = 5307-14-2)
positive (preliminary result of NCI)
NH2
NO2
L~J
NH2
REFERENCES
14
SHORT TERM TESTS
Salmonella (Ames)
Escherichia coli
Yeast
Chinese hamster
cells
Sister chromatid
exchan9e in Chinese
hamster cells
Mouse lymphoma
Mouse cells
Human lymphocytes
RESULTS
mutagen
(TA1538 +S9: 700 revertants/50 ~ig [1])
mutagen
mutagen
chromosome aberration
positive 16
1 ,20
13
27
7,9
mutagen
showed chromosomal breakage and had
exchange figures, morphological
transformation observed
chromosomal aberration observed
15
2
19
Reference to use in hair dyes
1 ,23
PAGENO="0415"
SHORT TERM TESTS
Salmonella (Ames)
Escherichia cpfl
Yeast
Drosophi 1 a
Mouse lymphoma
Mouse cells
1 ,20
13
27
3,5
15
2
7,9
16
409
NH2
4-nitro-o-phenylenediamine NH2
0
CANCER TEST (~cI# C03941) N02
(CAS# = 99-56-9)
test has been completed; results have not been announced as yet
RE FE REN C ES
14
RESULTS
mutagen
(TA1538: 3300 revertants/50 ~tg [1])
mutagen
mutagen
mutagen
mutagen
significant number of chromosome
breaks and rearrangements,
morphological tra~isformatiOnS observed
chromosomal damage (breaks and
exchanges), aberrations
positive
Chinese hamster
Sister chromatid
exchange in Chinese
hamster cells
Reference to use in hair dyes
1 ,23
PAGENO="0416"
410
NH2
o-phenylenediamine NH2 .RC].
CANCER TEST* REFERENCES
positive (preliminary NCI result) 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) mutagen 1,20,22
(TA1538 +59: 145 revertants/lOO ~ig [1])
mutagenic activity was increased when 22
peroxide was added
Reference to use in hair dyes
* Note: o-phenylenediamine is listed as NCI Compound 25 in NC~ Technical
Reports, September 1976
PAGENO="0417"
CANCER TEST
not under test by NCI
411
2ami no-S-ni trophenol
NO2 ~
SHORT TERM TESTS
Salmonella (Ames)
RESULTS
mutagen
REFERENCES
1 ,20
Reference to use in hair dyes
PAGENO="0418"
412
2-amino~4-nitropheno1
NO2
CANCER TEST REFERENCES
not under test by MCI
SHORT TERM TESTS RESULTS
Salmonella (Ames) mutagen 1,20
Reference to use in hair dyes 1
PAGENO="0419"
C~~i~SI ~NCT# C03963)
pøs~tive (pre~1mfn~ry ,~e~u1t)
SH0~T TERM, 1E~TS
Tiorleli a iAm~1
SLJ~IS
muta~efl
(1A1538 +$~ 50 ~`evè~tants/100 ~kç~ [6])
6,20,25
Reference to use in heir dyes
10
41~3
4-amin~-2~ni trop.hertOl
~FE~tNCES
14
PAGENO="0420"
414
NH2 0 NH2
Disperse Blue #1
(1 ,4,5,8-tetraaminoanthraquinone) Q
NH2 0 NE2
CANCER TEST (NCI# = C54900) RErEREJ~CES~ES
under test 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) mutagen 24
(TA1 537 +S9)
Reference to use in hair dyes 23
PAGENO="0421"
415
Direct Black #38
CANCER TEST REFERENCES
positive 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) mutagen 25
(TA98 +S9: 294 revertants/100 ~g [25])
Reference to use in hair dyes 28
PAGENO="0422"
416
1~irect Blue #6
CANCER T~ST REFERENCES
posilive 14
SHORT TERM TESTS RESULTS
not tested
Reference to use in hajr dyes 28
PAGENO="0423"
4~ch1 oro-Ophenyl enëdiarhir~e
~ (NCI# CO~292)
positive (pre~iminary ~e~u1t)
417
14
SI1OJ~T, 1~ERr~ TE~r$~
~P11~1~8.. (i!ie~j
RESULTS
mutagen
(TA1538 +S9: 96 revertants/400 ~~g)
~fer'ence to u~e in hair dyes
10
25
PAGENO="0424"
o-anisidine
418
CANCER TEST (NCI# = C03747, hydrochloride)
(CAS# = 134-29-0)
positive (preliminary result)
__________________ RESULTS
__________________ mutagen
(TA1538 + Norharman +S9:
45 revertants/50 ~ig)
REFERENCES
14
SHORT TERM TESTS
Sa1mo~ne1la (Ames)
25
Reference to use in hair dyes
10
PAGENO="0425"
4th
N~phenyl .-p-phenylenediamine
CAP1CER TESt (NCI# C02233) REFERENcI$
negative (preliminary result) 14
SHORT TERM TESTS RESULTS
~1mone1la (Ame~) not, a mutagen
~eference to use In hair dyes 10
24-600 0 - 78 - 28
PAGENO="0426"
420
1 phenyl-3 methyl-5-pyrazolone
CANCER TE~1 REFERENCES
negative (preliminary result) 14
SHORT TERM TESTS RESULTS
Salmonella (Ames) not a mutagen 25
Reference to use in hair dyes 10
PAGENO="0427"
421
resorcinol
(1,3~banganedio1)
CN~CER TEST REFERENCES
negative 14
SHORT TERM TESTS RESULTS
S~1rn~ne11a (Ames) not a mutagen 1
Reference to use in hair dyes 10
PAGENO="0428"
422
OTHER HAIR DYE RELATED CHEMICALS UNDER STUDY BY NCI
Preliminary result Evidence of use
ncer test in hair dyes
C03758 p-anjsidine hydrochlorj~e 10
C03305 4~chi oro-m-phenylenediamine
P'p'(methylene)-bis~(N,N_
dimethylanil me)
C54911 Acid Orange #3 23
C04159 IC Blue #1
C54897 HC Blue #2
C54922 HC Red #3
PAGENO="0429"
423
REFERENCES
1. Ames, B. N., Kammen, H. 0., and Yamasaki, E. (1975): Hair dyes are
mutagenic: Identification of a variety of mutagenic Ingredients.
Proc. Natl. Acad~Sci. USA 72: 2423-2427.
2. BenedIct, W. F. (1976): Morphological transformation and chromosome
aberrations produced by two hair dye components. Nature~Q,: 368-369.
3. Bli,jleven, W. 0. H. (1977): Mutageniclty of four hair dyes in
Drosophila rne1anogaste~. Mutat. ~ 48: 181-186.
4. Dybing, E., and Thorgelrsson, S. S. (1977): Metabolic activation of
2,4-diaminoanisole, a hair-dye component. I. Role of cytochrome P-450
metabolism in mutagenicity ~p,vi~rp~. Blochem., Phar,~. 26: 729-734.
5. Fahmy, M. J., and F~ahmy, 0. G. (1977): Mutagenicity of hair dye components
relative to the carcinogen benzidine in Drosophi1a~anoq~$i~~.
Mutat. Res. 56t 31-38.
6. Garner, R. C., and Nutman, C. A. (1977): TestIng of some azo dyes and
their reduction `products for mutagenicity using ~pionei,,.typ,h1mur1i~!,
TA 1538. Mutat, Res. 44: 9-19.
7. Ishidate, M., Jr., and Odashima, S. (1977): Chromosome tests with 134
compounds on Chinese hamster cells i~yj~.r~--a screening test for
chemical carcinogens. ~ ~ 337-354.
8. Ito, N., Hiasa, Y., Konishi, Y., and Maruganii, M. (1969): The development
of carcinoma In liver of rats treated with rn-toluylenediamlne and the
synergistic and antagonistic effects with other chemicals. c~rcer,
Research 29: 1137-1145.
PAGENO="0430"
424
9. Kirkland, D. J., and Venitt, S. (1976): Cytotoxicity of hair colourant
constituents: Chromosome damage induced by two nitrophenylenedlamines
in dultur~d Chinese hamster cells. Mutat. Res. 40: 47-56.
10. Narzulli, F. N., Green, S., and Maibach, H. I. (1978): Hair dye
toxicology. In Hair and Hair Disease, C. E. Orfanos, ed. (Stuttgart
and New York: Gustav Fischer Verlag, in press).
11. Matheson, D., and Creasy, B. (1976): Use of the LS17GY (TK~"') mouse
1ym~homa cell line coupled with an in vitro microsomal enzyme activation
system to study chemical promutagens. Paper presented at the Seventh
Annual Meeting of the Environmental Mutagen Society, March 12-15, 1976,
Atlanta, Georgia.
12. Merck Index (1976). Ninth edition. F~ahway, New Jersey: Merck & Co., Inc.
13. Mohn, 0. R., and de Serres, F. J. (1975): On the mutagenk activity of
some hair dyes. Paper presented at the Fifth Annual Meeting of the
European Environmental Mutagen Society in Florence, Italy.
14. NCI Bioassay Program. Richard A. Grie~emer, Associate Director for
Carcinogenesis Testing Program, Division of Cancer Cause and Prevention,
National Institutes of Health, Bethesda, Maryland 20014.
15. Palmer, K. A., Denunzio, A., and Green, S. (in press). The mutagenic
assay of some hair dye components using the thymidine Kinase 1ocu~ of
L5178Y mouse lymphoma cells. J.Env, Path. and Toxico1~
16. Perry, P. E., and Searle, C. E. (1977): Introduction of sister chromatid
exchanges. in Chinese hamster cells by the hair dye constituents 2-nitro-p-
pheny1ene~liamine and 4-nitro-o-phenylenediamine. Mutat. Res. 56: 20~-21O.
PAGENO="0431"
425
17, Pienta, R. J,, Shah, ti, J., Lebherz~ N, B., UI, and Andrews, A. W.
(1977): Correlaticrn ~f bacterial mutagenicity and hamster cell trans~
fprmation with tumorigenicity induced by 2,4-toluenediamine. Cancer
Letters 3: 45-52,
18. Saruta, N., Yamaguchi, S., and Nakatomi, V. (1958): Sarcoma produced
by subdermal administr~tiOfl of p~raphenylenediamine. K1ushuJ. Med,Sci,
9: 94.
19. Searle, C, E., Harnden, 0. 6., Venltt, S., and Gyde, 0. H. B. (1975):
Carcinogenicity and niutagenicitY tests of some hair colourantS and
constituents. Nature 255: 506-507.
20. Sugimura, T. (1975). Paper presented at the Fourth Joint Conference for
Evaluating Environmental tlutagenesls and Carcinogenesis, Seattle,
Washington,
21, Umeda, N. (1955): Production of rat sarcoma by injections of propylene
glycol solution of rn.toluenediamine, GAMN~: 597-606.
22. Venitt, S., and Searle, C. E. (1976). Mutagenicity and possible
carcinogenicitY of hair colourants and constituents. INSERM Symposia
Series, Vol, 52, IARC Scientific Publications No. 13. Envirl
PollutIon and CarciflQg~pj9 Risk, pp. 263-272.
23. Wernick, T., Lanman, B. N,, and Fraux, J, L, (1975). Chronic toxicity,
teratolo9ic, and reproduction studies with hair dyes. Ig~col.Al.
Pharmacol. 32: 450-460.
24. Brown, J. P., and Brown, R. J. (1976), Mutagenesis by 9,10_anthraquinofle
derivatives and related compounds in Salmonefla tyfihlmurium. Mutat.Re$,
40: 203-224.
PAGENO="0432"
426
2S. Yamasaki, E., and Ames, B. N. (unpublished).
26. Inouye, M., and Murakami, U. (1977): Teratogenicity of 2,5-diaminotoluene,
a hair-dye constituent in mice. Fd. Cosmet. Toxicol. 15: 447-451.
27. Vernon Mayer, FDA, personal communication 10/20/77 with Or. J. Highland,
from Testimony of the ~nvironmental Defense Fund Before the Subcommittee
on Oversight and Investigation of the House Committee on Interstate and
Foreign Commerce on the Subject of Cosmetic Safety. January 25, 1976.
28. Cancer and coal tar hair dyes: An unregulated hazard to consumers.
U.s, Gener4l Accounting Office, December ~, 1977. (From EDF reference in
#27.)
PAGENO="0433"
`Proc. Nc~ Amid. 8cs~ USA
Vol 72, No. 6, pp. 2423-2427, June 1975
427
Hair Dyes Are Mutagenic: Identification of a Variety of Mutagenic Ingredients
Qsairdyea as poasibiehuinan carcinogens and mutagene/2,4.ilianxinoanleole/2,4..dismi,iotoluone)
BIIUCE N. AMES, H. 0. KATVIMEN, AND EDITh YAMASAKE
Biochemistry Department, Ui,iversity of (~aiifornia, Berkeley, Calif. 54720 5
Contributed by Itruce N. Amoco, 111 arch 13, 1076
ABSTRACT We have previously described a sensitive
bacterial teat for detecting carcinogens as snutagens. We
chow here that 89% (150/169) of contmuercialoxidative..iype
(hydrogen peroxide) hair dye, formulations are mmmtagenic
in this teat. Of the 18 coniponents of these lists dyes, nine
show varioua degrees of mutagenicitys 2,4-dian,inoanisolc,
4..nitro..o.plsenyiencdianiine, 2-nitro-p-phonylcne,ii.
amine, 2,5-diaminoanls,sle, 2-amino.5.nitrophenol, en-
phenylenediamine, o-phenylenedian,inc, 2-amino.4-
nitrephenol, and 2,5-diaminotoluene, Three hair dye com-
ponents (p~phenyienediamine, 2,5-diaminotoiuene, and
2,5-diaoninoanisole) become strongly mutsgenic after
oxidation by lt,O,s tue mutagenic product of p-phenyiene..
diasnine is identified as the known trinser, Bsndrowskl's
base. 2,4*Diaminotoiuene, a -hair dye component until
recently, is also shown to be mutagenics this compound
has been shown to be a carcinogen in rats, and is used in
large amounts in the polyurethane foam industry. About
20,000,000 people (mostly women), dye their hair in the
U.S. and the hag*rd could be, considerable if these chcsni.
eels areactualiy mutagenleand carcinogenic in humans.
We have previously described a very sem~sitive and simph'
bacterial test for detecting chemical mutagelie (1-3), Ph'
compounds are tested on petri idats with specially cum-
strutted mutants of Salmonella typhisturism no tester straits.
Several tester straits were selected for sensitivity awl timed.
fleity in being reverted from a histidi,,c' requirement back to
prototrophy by a variety of mnutageur, One strain (TA1535)
detects mutagene lancing base-pair subetitutione and two
(TA1537 and TA1538) detect various- kinds of framrshift
mutagens. In additiosi to the histiditmo mutation, we have
added to each tester strain two additional mutations that
greatly Increase its sensitivity to mutagens: otto causes lose
of the excision repair system and the other loss of the iipo.
polysaecharide barrier that coats the surface of the bat-
tern (2).
A large number of carcinogens have been shown to be
mutagens which cause base-pair substitutions in our test
(1-3). Other earcinogenswitharomaticrings have been shows,
to cause fraineshift mutations (2-6). We have showi, that by
adding a microsontal activation system of rat (or lttssmmast
autopsy) liver tothe petri plates, a wide varietyofearoinogene
can be detected as scutagens after they have been mn,'tnb-
olized to their active forms (refo. 3, 7-9; amid unpublished
data~. Thus, an important sheet of mammalian motaboliossi
can be duplicated in an in vitro test.
The present work stems from a biochemistry class experi-
ment in which hundreds of commercial products were tented
for mutagenicity. Only two iwoducts were found to be touts-
genie: cigarette smoke tar (8) and-nit oxidative-typc hair dyo.
Since 20,000,000 people (10), main'y women, dye their Isair -
in the ~1.S. we have made a detailed study of hair dye mute.
gemlicity.
`lIe two usia types of lair lyre sro tic "semi.pcrnnanrit'' -
it lirect `lot dyes ml il "ix'rsntstet" or oxilative-type
dyes is, which 1i50, is usem~ ttt oxidize ttrsttttitic (hatnnmrs will,
tie prsehssctiost of larg,'r ,tl,,r,',l ss,ohecsml,,o whirls ire trappc(i
is tIme hair olmaft. V,~s have com,ctsttrate,l 0mm tIme oxidative-
type dyes simmer they ace(sszt for about 750/c (11) of the
$250,000,000/year lair dye smmrkct. `i'l,c oxid,,tive lye pack-
agt cossiists of cern bottle gosttais,ittg a mixture of aromatic
tsntsmeo, aromatic J,itro sls'rivatives, and phestols iii a vehicle
liqssitl (12, 13), mttsi a bottle of 11,0, with whirl, it is mixed
insmneliately before moe.
REStJL'i'S
We first te'otsMl must 3(1 e,ximlativm'-type l,air lye fom'smmulatiomss
fir reves'sisss~ of sir ,mtas,,lar,l toter ,`t-stmsmie. Alimost all of
lIen' wets' sm,utagetit' n-I,,', teote,l os st-miss TA1538, i,,,Iicat-
itsg tIme lrodctits of fs'tssnesl~ift-ty~s' - mutation. Strait
`l'Ah53.5 ems ,s,t rev,'rt.,.,l, isahieatis,g a lack of base-pair
sssl,stittmtitm, ssmsmtathmt,o; tIn' ,mth,'r frasn,'slift tests'r strain,
`i'Ah1137, wills a tliilt'r'nI s~o',ihicity Is,, mess sot reverlel,
We lniv,', tl,,'r,'form., owl strait, .TAI53K I, test 169 ,liiT,'r,'nt
oxhhativm'4y~o' sly' formt,jslntlosis; t-lmm'sc memo' all tim l1rsxl,a'ts
we eosmld fistsl its two heal 1mg stores. E,tslm l,air lye ltr'ltara-
tin,, Its seem listed botlm before amni aftm.m mixing with, 11,0,.
A fs'w typical exatm,plt'o ace simow, in Table I a,,td Fig. 1.
Ahsmiset all sf time dyes wire s1lmite snistagemie: 150 of 169 tested
sir 20%, mmd almost mill retais,t'h activity miter pes'oxile treat-
ssss's~t. We testeth prtohmsrt litton of eight thifferesst ,`oms,m,assies:
(-`imsimol lime. (Mhnss,lnsm-is, `l'om,,'r Natssrahly ihio,mde, Miss
(ittiroi (`recite Forsmnla litmir (~smlor lIatim, ilahsasmm (~olor
(`ostditiosmimtg Shmatstpoo-itt lhnirenlor, (`owe Tosser Salos~
Forsmmnha Oil i$Imasnpsos `l'imtt, ihorsm llhomm,hm Lotiom, `!`os,er, `I'rsme
Ibrummetto Time `l'rsme-('oior ihitir Color, Nice's, Easy); Jolts 11.
hhreck, lsmc. (Iheatstifmsi Ihair ilrcek hair (~olor); Revlomm
(Revlon cohorsilk); Ahbem't~-CuhPer (`o. (For Iirtssmettes Only);
`Fussy Cosmetics, lime. (Ogiht'ic Shanmpoo-im, (`onshitioeimtg
hair Color); (`ossmmmtir, isse, (L'Ors'ah l5referemice l5ertnastestt
(`resmue-im, iistireohssr, L'Oreal Exeelhs'm,ee l't'rssssts'mtt hair
(`csissr); `rite (uiihettc' (n (`l'ommi Shtamnltcmo-casy lhaire-ohtsri,mg
for lstn,sa'mtt (`oler); ltoimx l4ml,orttt,ries 1st. (ltosmx fasteitonc
cr55155' Hair `lint). Mntngem,ie hmmtir slyt.s were fotmm,sl in every
hair thye h,rohlmct line tinted. `l'abhsm I shows that sonic of thìe
hyes were mmumtagemmie tlim'eethy, witimout msmicronosmumi aetiva-
tloms, wlscreas titers requiresl mnicroeomai aetivatios, (athditlomm
of 6-9 mix). ha athhitioss, sonic of time thyes Were m~ot mtstagcit~e
umstli they were mm,ix,'tI with hi./)s. `l'Itsms, tlmem'e msisst se at
least three hitlerm'mmt iigri'shk'mtts resisomioibsbe for sssstngesmicity.
Eighsteest shihfes'esst s,hss'ntis'alo are seed is oxitl,stivsm hs,mir dyes
Its tIme U.S. us mishshitk,sm to limOs misish tIssue 1mm tIme vs'h,lcle
liquid (C. Burnett, jmer~omnl eomsmssummlesttiomm), aismsi imshtsstry
PAGENO="0434"
428
Medical Sciences: Ames .1 aL Ppoc. Na& Aced. Sci. USA 72(1975)
f--ayMS Brsse Ttnne 1. Mulagenic aclivily of hair dyes
- in reverting stPain TAJSS8
4 Revestant colonies per spot°
I Mixedwith
I Hair dyof Ha04
-59 +89 -59 +59
Medium Golden Brown no. 612 555 176 294 173
(Clairol Balsam Color)
Natural Dark Brown no. 120 131 151 84 244
4 (Clairol Nios'N Easy)
Pale Ash Blonde no. 120 2 69 0 35
* (Toni Innocent Color)
MediumBrownilo.17 0 3 0 267
(Breck Shampoo.in Hair Color)
Fr Light Golden Brown no. 7 4 0 0 3
(Breck Shampoo.in Hair Color)
Pro. 1. S5ot tests on petri plates showing the mutagenicity of
various hair dyes on strain TA1538: Moonhase no. 32 (Miss * Control values have been subtracted (<12 colonies). The
Clairol), Moonlit Mink no. 360 (Clairol Born Blonde), Wild dyes were found to be sterile. Values greater than 10 colonies
Fire no.32 ltoux fancitone) (all tested without peroxide), and overthe control valuewereinterpreted aspositive.
Frivolous Fawn no.23 (Roux fancitone) (mixed with H,O, as per t A drop (about 40 pl) of a freshly opened bottle of hair color
instructions). The procedure was as described in Table 1. Con- was spotted on a petri plate containing tester strain TA1538
tool plates without hair dyes are on the right. Plates B, but not in a thin agar overlay (3) and, where indicated, 5.9 Mix (3)con-
A, contain liver microsomes (S.9 Mix). Smokey Ash Brown no. taming ~at liver homogenate from rate induced with Aroclor
775 end Natural Black no.83 (Clairol Loving Care) are semi- l254wasadded (8).
permanent, non.oxidativetypedyes(seetexl). (The hair dye was mixed (in a sterile tube) with an equal
volume of hydrogen peroxide supplied by the manufacturer,
has kindly supplied them to us. The results of mutagenicity as per instructions. Since the drop size was the same (40 grl),
tests are shown in FIg. 2. Nine of the hair dye chemicals the numbere should be doubled to make them comparable to the
tested are mutagenic and their potenciea in reverting ~ uninixeddye.
TAl538covera200-foldrange. Wealsoshow the mutagenicity .
of 2,4.dzamsnotoluene, a chemical that was removed from hair
________ _____________________ dyes in 1971 after it was shown to be a carcinogen when fed
* to rats (14). The hair dye component that was most active
4055 400 in reverting TA1538 is the very closely related compound 2,4-
/ / .noarsn diaminoanisole (a CH5O- group is substituted for a CII,-
/L / group) which we find is about 30 times more active than the
I // / toluene derivative. Addition of human (3) or rat liver micro-
am II ioo / a~eacs.S.~. comes gives very similar results with these two compounds.
ee..ae // . / We have previously shown that many carcinogenic aromatic
.~ ~J ft / s~'s amines or aromatic nitro compounds revert strain TA1538
1 /1 / (3, 9). For example, we have repeated our dose-response
2005 // 20 / ~ curve for benxidine2HC1 (3), an aromatic diamine which is
.! / ~ / a carcinogen for humans, and find it similar in activity to
~ I I as45 . .,ssnsz m-phenylenediamine. The dose-response curves have been
1, / duplicated with the purest chemicals available commercially
ices fj zoo / (Aldrich orEsstman).Nevertheless,manyofthes000mpOunds
1 7 . ~ are easily oxidized in sir and it is quite poesible that these
/ - °~ (or other) impurities could account for the inutagenicity of
______ some of the less active compounds (see below).
0~ z~o e~ so ~ The aromatic amines (Fig. 2) all require activation with
mcrcsomes (5-9) for mutagenesis; this is characteristic of a
5,55405 Csngs,i,id 555 POtTS Plate variety of aromatic amine carcinogens (3, 5, 7-9). Nitro
Foo.2. Dost-vesponas curves of the mutagsnicity of hair dye carcinogens, such as 2-nitrofiuorene, mutate the bacteria
dssanicals for tester strain TA1538. Reversion was determined without inicrosomal activation (2, 9) because the bacteria
on petit plates by incorporating the chemical mutagen, bacteria, contain nitro reductases which activate them (asdo roam-
and microsoanal activation system where indicated (ass legend to malian cells). Thus, 4-nitro-o.phenylenediamine could account
~ R~tewere~7