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CITIZEN PETITION SEEKING
CANCER WARNING ON
COSMETICS CONTAINING
Cocoamide DEA
David A. Kessler, M.D. Commissioner, Food and Drug Administration
October 22, 1996
Room #14-71 Rockville, MD 20857
The undersigned submits on behalf of the
Cancer Prevention Coalition, Inc., and its Chairman, Samuel S. Epstein,
M.D., and on behalf of the Center for Constitutional Rights, Michael
Deutsch, Esquire. This petition is based on scientific evidence of
increased cancer risks from exposure to nitrosamines in cosmetics.
The undersigned submits this petition under 21 U.S.C. 321 (n), 361, 362
and 371 (a); and 21 CFR 740.1, 740.2 of 21 CFR 10.30 of the Federal
Food, Drug, and Cosmetic Act to the Commissioner of Food and Drugs
requiring that all cosmetic products containing diethanolamine (DEA)
bear labels with a warning: "Caution
-- This product may contain N-nitrosodiethanolamine, a known cancer
-causing agent."
A. AGENCY ACTION REQUESTED
This petition requests that FDA takes the following action:
(1) Issue a regulation under the Federal Food, Drug
and Cosmetic Act, Section 601(a), stating that "All cosmetics containing
diethanolamine (DEA), a constituent of diethanolamide soaps that may
react with nitrosating agents to form N-nitrosodiethanolamine (NDEA),
bear a label as an adulterated product containing poisonous and
deleterious substances 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: that which contains DEA
also bears the following legend conspicuously displayed thereon: 'Caution -- This product may contain
N-nitrosodi-ethanolamine, a known cancer-causing agent.'"
(2) For purposes of enforcement of this act, the
Secretary should conduct examinations and investigations of products
which may be contaminated with NDEA through regular and routine
analytical testing by officers and employees of the Department or
through any health, food, or drug officer or employee of any State,
Territory or political subdivision thereof, duly commissioned by the
Secretary of the Department. Such examinations should result in removal
of products from the shelves if products do not comply with labeling
regulations.
(3) Pursuant to 21 CFR 10.30 (h) (2), a
hearing at which time we can present our scientific evidence.
B. STATEMENT OF GROUNDS
Widespread Contamination of Cosmetics with DEA and NDEA
Diethanolamine (DEA) is a high production chemical used in a wide range
of cosmetic pro-ducts, including shampoos, lotions and creams. In the
presence of long-chain fatty acids DEA reacts to form neutral
ethanolamide soaps, which are used as wetting agents in cosmetics. These
soaps contain unreacted DEA. Triethanolamine (TEA), also used widely in
cosmetics, may also be contaminated with DEA.1According to
the Cosmetics, Toiletries and Fragrance Association,
Cocamide DEA, Lauramide DEA,
Linoleamide DEA and Oleamide DEA are fatty acid
diethanolamides which may contain 4 to 33 percent diethanolamine. These
ingredients are used in cosmetics at concentrations of <0.1 percent to
50 percent, with most products containing 1 percent to 25 percent
diethanolamide.2
As of 1980, FDA reported that approximately 42 percent of all cosmetic
products were contaminated with NDEA at the following concentrations:
facial cosmetics from .042 to 49 mg/kg, lotions from less than .010 to
.140 mg/kg, shampoos from less than 10 to 160 mg/kg.3 In two
surveys of cosmetics, 27 out of 29 American products contained up to 48
mg/kg NDEA.4 A more recent FDA analysis (1991-1992) found
that NDEA is present in some products at mg/kg concentrations.5
DEA IS A PRECURSOR OF NDEA
N-nitrosodiethanolamine (NDEA), is readily formed in cosmetic by
nitrosation of DEA. Even small amounts of DEA in cosmetics can react
with nitrosating agents to form nitrosamines. According to the
Cosmetics, Toiletries and Fragrance Association: Nitrosamine
contamination of diethanolamine and fatty acid diethanolamides, and
nitrosamine formation are potential problems in using these
diethanolamides. The diethanolamides used in cosmetic products should be
free of nitrosamines, and the finished product should not contain
nitrosating agents as ingredients.
6
Nitrosating agents are added to cosmetics in one of three ways: (a)
Nitrites are added directly as anti-corrosive agents; (b) Nitrites are
released by the degradation of 2-nitro-1,3-propanediol (BNDP); and (c)
Nitrites are contaminants in the raw materials or resulting from the
exposure of cosmetics to air. Secondary amines, such as DEA, are rapidly
nitrosated by nitrogen oxides. Nitrosamines formation from nitrite and
amines is accelerated under specific conditions by formaldehyde,
paraformaldehyde, thiocyanate, nitrophenols and certain metal salts (e.g
ZnI2, CuCl, AgNO3, SnCl2 and HgCl2).7,8,9,10,11
Cosmetics remain on store shelves and in cabinets of consumers for long
periods of time, allowing nitrosamines to form. If DEA is present,
nitrosamines can continue to form throughout storage, especially at
elevated temperatures.12
Acidic pH is an optimal reaction condition for nitrosamine formation.
Although cosmetics generally have neutral pH, 13
N-nitrosamines can be formed at neutral or alkaline pH by the reaction
of a nitrosating agent with an amine in the presence of carbonyl
compounds such as formaldehyde.14,15 Formaldehyde is
present in cosmetics either from in situ formaldehyde-releasing
agents, such as BNDP, or from its use as a preservative.16
DERMAL ABSORPTION OF NDEA
There is substantial evidence of the dermal absorption of NDEA in both
rodents and humans. "[NDEA] is
a known carcinogen in laboratory animals; it is absorbed through the
skin. The absorption rate is a function of the nature of the cosmetic;
absorption is fastest in nonpolar vehicles".17 Dermal absorption of
NDEA was demonstrated by Lijinsky et al. In 1981.18 As
a fat-soluble chemical NDEA can be absorbed dermally in rats and humans.19,20
NDEA INCREASES CANCER RISK
There is substantial evidence of potent carcinogenicity of NDEA in a
wide range of animal species.21,22, 23, 24, 25, 26, 27, 28, 29
According to the International Agency for Research on Cancer (IARC).
There is sufficient evidence of a carcinogenic effect of
N-nitrosodiethanolamine -- . In view of the widespread exposure to
appreciable concentrations of N-nitrosodiethanol-amine, efforts should
be made to obtain epidemiological information.30
The National Toxicology Program similarly concluded: AThere is sufficient evidence for the
carcinogenicity of N-nitrosodiethanolamine in experimental animals.31
Of over 44 different species in which N-nitroso compounds have been
tested, all have been susceptible. 32
Humans are most unlikely to be the only exception to this trend.
In 1978, the IARC concluded that "although no epidemiological data were
available, nitrosodiethanolamine should be regarded for practical
purposes as if it were carcinogenic to humans".33 In 1987
the IARC further confirmed the carcinogenicity of NDEA.
Based on early evidence of the carcinogenicity of NDEA and evidence of
cutting fluid contamination, 20 years ago NIOSH recommended that action
be taken to protect workers including elimination of nitrosamines from
the fluids.34 More recently, NIOSH published a hazard
review of cutting fluids used in metal working that contain NDEA among
other nitrosamines. This hazard review indicates that, based on
epidemiological evidence in human beings, "Increased cancer risk has been
generally attributed to worker exposure to nitrosamine or PAH (polyaromatic
hydrocarbon) contaminants in metal working fluids".35
THE FAILURE OF THE FDA TO TAKE APPROPRIATE REGULATORY
ACTION
In the Federal Register of April 10, 1979, the FDA called for
industry "to take immediate
measures to eliminate to the extent possible [NDEA] and any other
N-nitrosamines from cosmetic products," and further insisted that "cosmetic products may be analyzed by
FDA for nitrosamine contamination and that individual products could be
subject to enforcement action."
FDA has taken no subsequent enforcement actions despite the limited
compliance with this Federal Register order. According to the FDA
officials Don Havery and Hardy Chou in 1994.
In the United States...the personal care industry has invested
resources in understanding both the mechanisms of N-nitrosamine
formation in cosmetic systems and the means of inhibiting N-nitrosamine
formation. However, there is still room for improvement. New products
containing nitrosatable amines with formaldehyde and nitrite-releasing
preservatives are still appearing on the U.S. market. Manufacturers have
a responsibility to be aware of the potential for N-nitrosamine
formation and to take steps necessary to keep N-nitrosamine levels as
low as possible as part of their good manufacturing practices.36
The goal of good manufacturing practices is to reduce "human exposure to N-nitrosamines to
the lowest level technologically feasible by reducing levels in all
personal care products. With the information and technology currently
available to cosmetic manufacturers, N-nitrosamine levels can and should
be further reduced in consumer products".37
The FDA has failed to act on the Federal Register
recommendations made in 1979. More recently, the FDA has not fully
recognized the consumer hazards of this carcinogen. Measurements have
not been made to determine total daily exposure to nitrosamines and it
is inappropriate to quantify exposures without such data.
COSMETIC INDUSTRY RESPONSE TO FDA ACTION
In response to the FDA Federal Register order, the Nitrosamine
Task Force of the Cosmetics, Toiletries and Fragrance Association failed
to eliminate the use of DEA, but rather, they investigated ways to
inhibit the formation of NDEA. 38
There are no known nitrosation inhibitors that eliminate nitrosamine
contamination. Inhibitors have failed for the following reasons:
Commercially available products from the German market
analyzed six to 18 months after the recommendation had been
issued showed that only 15 percent were contaminated with [NDEA]
or NDHPA.... The overall results of this
study demonstrate however, a strong downward trend in both
levels and frequency of contamination. They prove that
nitrosamine contamination of cosmetics can be minimized by
simple preventive measures
The European Union has stated specific maximum allowable concentrations
of inadvertently formed N-nitrosodialkanolamine. In legislation that was
most recently amended in 1993, the European Union asserted that
monoalkanolamines and trialkanolamines must be stored in nitrite free
containers, cannot be used in nitrosating systems, must have purity of
at least 99% and can contain no more than .5% secondary alkanolamine.
With regards to N-nitrosodialkanolamine specifically, the maximum
content that the EU allows is 50 micrograms per kilogram (50ppb).50
In comparison, U.S. cosmetic levels for NDEA as high as 2,960 parts per
billion were reported in 1992.51
CONCLUSION
There is strong evidence proving: the widespread use of DEA in
cosmetics, nitrosation of DEA to form NDEA, contamination of cosmetics
with NDEA, the potent carcinogenicity of NDEA, and the availability of
alternatives to DEA. The FDA should take prompt action to require labels
on all products containing DEA that reads: "Caution -- This product may contain
N-nitrosodi-ethanolamine, a known cancer-causing agent."
C. CLAIM FOR CATEGORICAL EXCLUSION
A claim for categorical exclusion is asserted pursuant to 21 CFR 25.24
(a)(11).
D. CERTIFICATION
The undersigned certifies, that, to the best knowledge and belief of
the undersigned, this petition includes all information and views on
which the petition relies, and that it includes representative data and
information known to the petitioner which are unfavorable to the
petition.
This petition is submitted by:
Samuel S. Epstein, M.D.
Michael Deutsch, Esq. Legal Director, Counsel for Constitutional
Rights, New York
REFERENCES
The European Union has stated specific maximum allowable concentrations
of inadvertently formed N-nitrosodialkanolamine. In legislation that was
most recently amended in 1993, the European Union asserted that
monoalkanolamines and trialkanolamines must be stored in nitrite free
containers, cannot be used in nitrosating systems, must have purity of
at least 99% and can contain no more than .5% secondary alkanolamine.
With regards to N-nitrosodialkanolamine specifically, the maximum
content that the EU allows is 50 micrograms per kilogram (50ppb).50
In comparison, U.S. cosmetic levels for NDEA as high as 2,960 parts per
billion were reported in 1992.51
CONCLUSION
There is strong evidence proving: the widespread use of DEA in
cosmetics, nitrosation of DEA to form NDEA, contamination of cosmetics
with NDEA, the potent carcinogenicity of NDEA, and the availability of
alternatives to DEA. The FDA should take prompt action to require labels
on all products containing DEA that reads: "Caution -- This product may contain
N-nitrosodi-ethanolamine, a known cancer-causing agent."
C. CLAIM FOR CATEGORICAL EXCLUSION
A claim for categorical exclusion is asserted pursuant to 21 CFR 25.24
(a)(11).
D. CERTIFICATION
The undersigned certifies, that, to the best knowledge and belief of
the undersigned, this petition includes all information and views on
which the petition relies, and that it includes representative data and
information known to the petitioner which are unfavorable to the
petition.
This petition is submitted by:
Samuel S. Epstein, M.D.
Michael Deutsch, Esq. Legal Director, Counsel for Constitutional
Rights, New York
REFERENCES
The European Union has stated specific maximum allowable concentrations
of inadvertently formed N-nitrosodialkanolamine. In legislation that was
most recently amended in 1993, the European Union asserted that
monoalkanolamines and trialkanolamines must be stored in nitrite free
containers, cannot be used in nitrosating systems, must have purity of
at least 99% and can contain no more than .5% secondary alkanolamine.
With regards to N-nitrosodialkanolamine specifically, the maximum
content that the EU allows is 50 micrograms per kilogram (50ppb).50
In comparison, U.S. cosmetic levels for NDEA as high as 2,960 parts per
billion were reported in 1992.51
CONCLUSION
There is strong evidence proving: the widespread use of DEA in
cosmetics, nitrosation of DEA to form NDEA, contamination of cosmetics
with NDEA, the potent carcinogenicity of NDEA, and the availability of
alternatives to DEA. The FDA should take prompt action to require labels
on all products containing DEA that reads: "Caution -- This product may contain
N-nitrosodi-ethanolamine, a known cancer-causing agent."
C. CLAIM FOR CATEGORICAL EXCLUSION
A claim for categorical exclusion is asserted pursuant to 21 CFR 25.24
(a)(11).
D. CERTIFICATION
The undersigned certifies, that, to the best knowledge and belief of
the undersigned, this petition includes all information and views on
which the petition relies, and that it includes representative data and
information known to the petitioner which are unfavorable to the
petition.
This petition is submitted by:
Samuel S. Epstein, M.D.
Michael Deutsch, Esq. Legal Director, Counsel for Constitutional
Rights, New York
REFERENCES
1. Havery, Donald C. and Chou, Hardy J. "N-Nitrosamines in Cosmetics Product."
Cosmetics & Toiletries, 109(5):53, May 1994.
2. Cosmetics, Toiletries and Fragrance Association. 1996 CIR
Compendium, Cosmetic Ingredient Review, Washington, D.C., 1996.
3. NTP, Seventh annual Report on Carcinogens. U.S. Department of
helth and Human Services, Public Health Services, natinal Toxicology
Program, National Institute of Environmental Health Sciences, Technical
Resources Inc., Rockville, MD 1994.
4. Eisenbrand, G., M. Blankar, H. Sommer, and B. Weber. "N-Nitrosoalkanolamines
in Cosmetics." In: Relevance to Human Cancer of N-nitroso Compounds,
tobacco Smoke and Mycotoxins, Ed. I.K. O'Neill, J. Chen and H. Bartsch.
International Agency for Research on Cancer , Lyon, 1991.
5. Havery, Donald C. and Hardy J. Chou. "Nitrosamines in Sunscreens and
Cosmetic Products." Nitrosamines and Related N-nitroso Compounds,,
ACS Monograph No. 553. Ed. Richard N. Loeppky and Christopher J.
Michejda. American Chemical Society, Washington, D.C., 1994.
6. Cosmetics, Toiletries and Fragrance Association. 1996 CIR
Compendium, Cosmetic Ingredient Review, Washington, D.C., 1996.
7. Keefer, L.K. and P.P. Roller, "N-Nitrosation by nitrite ion in
neutral and basic medium."
Science 181:1245-1246, 1973.
8. Archer, M.C. and J.D. Okum. "Kinetics of nitrosamine formation in
the presence of micelle-forming surfactants." Journal of the National
Cancer Institute 58:409, 1977. (Cited In: National Institutes
for Occupational Safety and Health. Draft Criteria for Recommended
Standards: Occupational Exposures to Metal Working Fluids. U.S.
Department of Health and Human Services, February 19, 1996.)
9. Davies, R. and D.J. McWeeny. "Catalytic effect of nitrosophenols on
N-nitrosamine formation." Nature 266:657-658, 1977. (Cited In: National
Institutes for Occupational Safety and Health. Draft Criteria for
Recommended Standards: Occupational Exposures to Metal Working
Fluids. U.S. Department of Health and Human Services, February 19,
1996).
10. Challis, B.D., A. Edward, R.R. Hunma, S.A. Kyrtopoulos, and J.R.
Outram. "Rapid formation of N-nitrosamines from nitrogen oxides under
neutral and alkaline conditions." IARC
Scientific Publication, Lyon, France, 19:127,
1978. (Cited In: National Institutes for Occupational Safety and
Health. Draft Criteria for Recommended Standards:
Occupational Exposures to Metal Working Fluids. U.S.
Department of Health and Human Services, February 19, 1996.)
11. Loeppky, R.N., T.J. Hansen, L.P. Keefer. "Reducing nitrosamine
contamination in cutting fluids." Fd. Cosmet. Toxicol.
21(5):607-613, 1983. (Cited In: National Institutes for
Occupational Safety and Health. Draft Criteria for Recommended
Standards: Occupational Exposures to Metal Working Fluids. U.S.
Department of Health and Human Services, February 19, 1996.)
12. Havery, Donald C. and Hardy J. Chou. "Nitrosamines in Sunscreens
and Cosmetic Products." Nitrosamines and Related N-nitroso Compounds,
ACS Monograph No. 553, Ed. Richard N. Loeppky and Christopher J.
Michejda. American Chemical Society, Washington, D.C. , 1994.
13. Havery, Donald C. and Hardy J. Chou. "N-Nitrosamines in Cosmetic
Products." Cosmetics & Toiletries, 109(5):53, May 1994.
14. Ibid.
15. Keefer, L.P. and P.P. Roller, "N-nitrosation by nitrite Ion in
Neutral and Basic Medium." Science, 181:1245-46, 1973.
16. Havery, Donald C. and Hardy J. Chou. "N-Nitrosamines in Cosmetic
Products." Cosmetics & Toiletries, 109(5):53, May 1994.
17. Havery, Donald C. and Hardy J. Chou. "Nitrosamines in Sunscreens
and Cosmetic Products." Nitrosamines and Related N-nitroso Compounds,,
ACS Monograph No. 553. Ed. Richard N. Loeppky and Christopher J.
Michejda. American Chemical Society, Washington, D.C., 1994.
18. Lijinsky, W., A.M. Losikoff, and E.B. Sansone. Journal of the
National Cancer Institute 66:125-127, 1981.
19. Edwards, G.S., M. Peng, D. J. Fine, B. Spiegelhalder, and J. Kann.
"Detection of N-nitroso-diethanolamine in human urine following
application of contaminated cosmetics." Toxicol. Lett.
4:217-222, 1979. (Cited In: National Institutes for Occupational
Safety and Health. Draft Criteria for Recommended Standards:
Occupational Exposures to Metal Working Fluids. U.S. Department of
health and Human Services, Feb. 19, 1996).
20. Preussman, R. "Occurrence and
Exposure to N-nitroso Compounds and Precursors." In: N-Nitroso
Compounds: Occurrence, Biological Effects and Relevance to Human
Cancer. Ed. I.K. O'Neill, R.C. Von Borstel, C.T. Miller, J.
Long and H. Bartsch, IARC Scientific publications No. 57, IARC,
Lyon, 1984.
21. Druckrey, H., R. Preussman, S. Ivankovic, and D. Schmahl. AOrganotrope Carcinogene Wirkungen Bei
65 verschiedenen N-Nitroso-verbindugen an BD-ratten. Z Krebsforsch
69:103-201, 1967. (Cited In: National Institutes for Occupational
Safety and Health. Draft Criteria for Recommended Standards:
Occupational Expousres to Metal Working Fluids. U.S. Department of
Health and Human Services, February 19, 1996.)
22. Hilfrich, J., I. Schmeltz, and D. Hoffmann. "Effects of N-nitrosodiethanolamine
and 1,2-diethanolhydrazine in Syrian golden Hamsters."Cancer Letters 4:55-60,
1978. (Cited In: National Institutes for Occupational Safety and Health.
Draft Criteria for Recommended Standards: Occupational Exposures to
metal Working Fluids. U.S. Department of Health and Human Services,
February 19, 1996.)
23. International Agency for Research on Cancer, Monograph on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some
N-nitroso Compounds 17:77-82, 1978.
24. Lijinsky, W. M.D. Reuber, and W.B. Manning. "Potent carcinogenicity of
nitrosodiethanolamine in rats."
Nature 288:589-590, 1980.
25. Pour, P. and L. Wallcave. "The carcinogenicity of
n-Nitrosodiethanolamine, An Environmental Pollutant, In Syrian Hamsters."
Cancer Letters
14:23-27, 1981.
26. Preussman,R., M. Habs, H. Habs, and D. Schmahl. "Carcinogenicity of
N-Nitrosodiethanolamine in Rats at Five Different Dose Levels."Cancer Research,
42:5167-5171, 1982.
27. Lijinsky, W. and M.D. Reuber, "Dose-response study with N-nitrosodiethanolamine
in F344 rats." Fd. Cosmet. Toxicol.
22(1):23-26, 1984.
28. Lijinsky, W. And R.M. Kovatch. "Induction of liver tumor in rats by
nitrosodiethanolamine at low doses." Carcinogenesis
6(12):1679-1681, 1985.
29. NTP, Seventh Annual Report on Carcinogens. U.S. Department
of Health and Human Services, Public Health Service, National Toxicology
Program, National Institute of Environmental Health Sciences, Technical
Resources Inc., Rockville, MD., 1994.
30. International Agency for Research on Cancer, Monograph on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some N-nitroso
Compounds 17:77-82, 1978.
31. NTP, Seventh Annual Report on Carcinogens. U.S. Department
of Health and Human Services, Public Health Service, National Toxicology
Program, National Institute of Environmental Health Sciences, Technical
Resources Inc., Rockville, MD., 1994.
32. Lijinsky, William. Chemistry and Biology of N-nitroso Compounds.
Cambridge University Press, New York, 1992.
33. International Agency for Research on Cancer, Monograph on the
Evaluation of the Carcinogenic Risk of Chemicals to Humans: Some N-nitroso
Compounds 17:77-82, 1978.
34. NIOSH. "Nitrosamines in Cutting Fluids." Current Intelligence
Bulletin, October 6, 1976.
35. NIOSH. Draft Criteria for Recommended Standards:
Occupational Exposures to Metal Working Fluids, U.S. Department of
Health and Human Services, Public Health Service, Center for Disease
Control and Prevention, National Institute for Occupational
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