Animal data on 2NPPD and 4NOPD and cosmetic hair dyes containing these ingredients suggest that both compounds were nonirritating to rabbit skin and eyes, but were sensitizers on guinea pig skin. The results of repeated insult patch tests with hair dye products containing these ingredients indicated that neither was an irritant or a sensitizer to human subjects as normally used. In the absence of human data on the pure compounds, however, 2NPPD and 4NOPD are considered to be potential human sensitizers.
Topically applied 2NPPD and 4NOPD are absorbed by experimental animals. Neither embryotoxicity nor teratogenicity was observed in animal studies when hair dyes containing 2NPPD and 4NOPD were applied to the skin. Both ingredients were mutagenic in some bacterial and in vitro mammalian systems; both compounds had some genotoxic activity. In feeding studies in mice and rats, only 2NPPD induced hepatocellular tumors in female mice. Both compounds were noncarcinogenic in male mice and in rats of either sex. Epidemiological data have not demonstrated a carcinogenic effect in man for hair dyes.
For those persons not sensitized, it is concluded that 2NPPD and 4NOPD are safe as hair dye ingredients at the current concentration of use.
2. INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC). (1978). IARC Monographs on the Carcinogenic Risk of Chemicals to Man. Some aromatic amines and related nitro compounds–Hair dyes, colouring agents and miscellaneous industrial chemicals. Lyon, France: IARC, Vol. 16.
3.
3. Windholz, M. (ed.). (1976). The Merck Index, 9th ed.Rahway, NJ: Merck & Co.
4.
4. COSMETIC, TOILETRY AND FRAGRANCE ASSOCIATION (CTFA). (November 16, 1982). Cosmetic ingredient chemical description, 2-nitro-p-phenylenediamine.*
5.
5. Greenburg, L.A., and Lester, D. (1954). Handbook of Cosmetic Materials.New York: Interscience Publishers.
6.
6. THE SOCIETY OF DYERS AND COLOURISTS. (1971). Colour Index, 3rd ed. Yorkshire, UK, Vol. 4.
7.
7. CTFA. (November 16, 1982). Cosmetic ingredient chemical description, 4-nitro-o-phenylenediamine.*
8.
8. Weast, R.C. (ed.). (1978). CRC Handbook of Chemistry and Physics, 5th ed.West Palm Beach, FL: CRC Press.
9.
9. Reio, L. (1970). Third supplement for the paper chromatographic separation and identification of phenol derivatives and related compounds of biochemical interest using a “reference system”. J. Chromatogr.47, 60–85.
10.
10. Turchetto, L., Cuozzo, V., Terracciano, M., Papetti, P., and Percaccio, G. (1978). Analytical study of certain hair dyes. Boll. Chim. Farm.117, 475–8.
11.
11. Midler, O., and Karleskind, A. (1978). Hair dyes acting by oxidation. Their identification and estimation by high-performance liquid phase chromatography. Parfums. Cosmet. Aromes23, 77–80, 83–5.
12.
12. Goldstein, S., Kopf, A.A., and Feinland, R. (April 21–23, 1968). Analysis of oxidation dyes in hair colorants by thin-layer and gas chromatography. Proc. Joint Conf. Cosmet. Sci. Washington, DC: Toilet Goods Assoc.
13.
13. Kottemann, C.M. (1966). Two-dimensional thin-layer chromatographic procedure for the identification of dye intermediates in arylamine oxidation hair dyes. J. Assoc. Off. Anal. Chem.49, 954–9.
14.
14. Lepri, L., Desideri, P.G., and Coas, V. (1974). Chromatographic and electrophoretic behavior of primary aromatic amines on anion-exchange thin layers. J. Chromatog.90, 331–9.
15.
15. Lepri, L., Desideri, P.G., and Coas, V. (1976). Separation and identification of coloring agents in the oxidation-type hair dyes by ion-exchange thin-layer chromatography. Ann. Chim. (Rome)66, 451–600.
16.
16. Pinter, I., and Kramer, M. (1966). Le dosage de quelques diamines aromatiques employees dans la teinture pour cheveux par chromatographie sur couche mince. Arch. Biochim. Cosmetol.9, 153–7.
17.
17. Pinter, I., and Kramer, M. (1967). The determination of some aromatic diamines used in hair dyes by thin-layer chromatography. Parfum. Cosmet. Savons10, 257–60.
19. Urquizo, S. (1969). Identification of some aromatic amines and phenolic compounds by thin-layer chromatography. Ann. Fals. Expert. Chim.62, 27–31.
20.
20. Zalazna, K., and Legatowa, B. (1971). Identification of basic dyes in emulsified hair dyes by thin layer chromatography. Rocz. Panstw. Zakl. Hig.22, 427–30.
21.
21. Iordanova, I. (1978). Quantitative determination of oxidative dyes in the hygienic evaluation of hair coloring cosmetic agents. Khig. Zdraveopaz.21, 83–7.
22.
22. Legatowa, B. (1973). Determination of aromatic amines and aminophenols in hair dyes. Rocz. Panstw. Zakl. Hig.24, 393–402.
23.
23. Corbett, J.F., and Menkart, J. (1973). Hair coloring. Cutis12:190–7.
24.
24. Markland, W.R. (1966). Hair preparations. In: Kirk-Othner Encyclopedia of Chemical Technology, 2nd ed.New York: Interscience Publishers, Vol. 10.
25.
25. NATIONAL CANCER INSTITUTE (NCI). (1979). Bioassay of 2-nitro-p-phenylenediamine for possible carcinogenicity. PB 290 304. Springfield, VA: National Technical Information Service (NTIS).
26.
26. NCI. (1979). Bioassay of 4-nitro-o-phenylenediamine for possible carcinogenicity. PB 290 306. Springfield, VA: NTIS.
30. Brown, K. (1982). Hair colorants. J. Soc. Cosmet. Chem.33, 375–83.
31.
31. Radomski, J.L. (1979). The primary aromatic amines: their biological properties and structure-activity relationships. Ann. Rev. Pharmacol. Toxicol.19, 129–57.
32.
32. Marzulli, F.N., Anjo, D.M., and Maibach, H.I. (1981). In vivo skin penetration studies of 2,4-toluenediamine, 2,4-diaminoanosile, 2-nitro-p-phenylenediamine, p-dioxane and N-nitrosodiethanolamine in cosmetics. Food Cosmet. Toxicol.19, 743–7.
33.
33. FOOD AND DRUG ADMINISTRATION (FDA). (December 22, 1981). Cosmetic product formulation data: (a) ingredients used in each product category, and (b) number of brand name products in each product code. Two computer printouts. Washington, DC.
34.
34. CONSUMER REPORTS. (1979). Are hair dyes safe? pp. 456–60.
35.
35. Menkart, J., and Lanman, B.M. (1977). Cancer and hair dyes. NY State J. Med.77, 366.
36.
36. FEDERAL REGISTER. (January 8, 1982). Phenylenediamines, response to Interagency Testing Committee47, 973–83.
37.
37. THE SOCIETY OF DYERS AND COLOURISTS. (1971). Color Index, 3rd ed. Yorkshire, UK, Vol. 3.
38.
38. Hockenhull, D.J.D., and Floodgate, G.D. (1952). o-Phenylenediamine and 1,2-diamino-4-nitrobenzene as reagents for α-keto acids. Biochem. J.52, 38–40.
39.
39. Taylor, K.W., and Smith, M.J.H. (1955). 1,2,-Diamino-4-nitrobenzene as a reagent for the detection and determination of α-keto acids in blood and urine. Analyst80, 607–13.
40.
40. Bourgeois, C.F., Czornomaz, A.M., George, P., Belliot, J.P., Mainguy, P.R., and Watier, B. (1975). Specific determination of vitamin C (ascorbic and dehydroascorbic acids) in foods. Analysis3, 540–8.
41.
41. Bourgeois, C.F., and Mainguy, P.R. (1975). Determination of vitamin C (ascorbic and dehydroascorbic acids) in foods and feeds. Int. J. Vit. Nutr. Res.45, 70–84.
42.
42. Lambert, J.L., Chejlava, M.J., Paukstelis, J.V., and Liu, A.T. (1978). 4-Nitro-1,2-diaminobenzene as a new chromagen in the West-Gaeke method for sulfur dioxide. Anal. Chim. Acta99, 379–82.
43.
43. Cappon, C.J., and Smith, J.C. (1978). Determination of selenium in biological materials by gas chromatography. J. Anal. Toxicol.2, 114–20.
44.
44. Shimoishi, Y. (1976). The gas-chromatographic determination of selenium (VI) and total selenium in milk, milk products and albumin with 1,2-diamino-4-nitrobenzene. Analyst101, 298–305.
45.
45. Nakao, M., and Takeda, Y. (1983). Distribution, excretion, and metabolism of nitro-p-phenylenediamine in rats. J. Toxicol. Environ. Health11, 93–100.
46.
46. Howes, D., and Black, J.G. (1983). Percutaneous absorption of 2-nitro-p-phenylenediamine. Int. J. Cosmet. Sci.5, 215–26.
47.
47. Wernick, T., Lanman, B.M., and Fraux, J.L. (1975). Chronic toxicity, teratologic, and reproduction studies with hair dyes. Toxicol. Appl. Pharmacol.32, 450–60.
48.
48. Ames, B.N., Mccann, J., and Yamasaki, E. (1975). Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat. Res.31, 347–64.
49.
49. Ammenheuser, M.M., and Warren, M.E. (1979). Detection of mutagens in the urine of rats following topical application of hair dyes. Mutat. Res.66, 241–5.
50.
50. Durston, W.E., and Ames, B.N. (1974). A simple method for the detection of mutagens in urine: studies with the carcinogen 2-acetylaminofluorene. Proc. Natl. Acad. Sci. USA71, 737–41.
51.
51. Burnett, C., Loehr, R., and Corbett, J. (1977). Dominant lethal mutgenicity study on hair dyes. J. Toxicol. Environ. Health2, 657–62.
52.
52. Gloxhuber, C., Potokar, M., Reese, G., and Flemming, P. (1972). Toxikologische prufung direktziehender haarfarbstoffe. J. Soc. Cosmet. Chem.23, 259–69.
53.
53. Lloyd, G.K., Liggett, M.P., Kynoch, S.R., and Davies, R.E. (1977). Assessment of the acute toxicity and potential irritancy of hair dye constituents. Food Cosmet. Toxicol.15, 607–10.
54.
54. Hodge, H.C., and Sterner, J.H. (1949). Tabulation of toxicity classes. Am. Ind. Hyg. A. Quart.10, 93–6.
55.
55. Reznik, G., and Ward, J.M. (1979). Carcinogenicity of the hair dye component 2-nitro-p-phenylenediamine: Induction of eosinophilic hepatocellular neoplasms in female B6C3F1 mice. Food Cosmet. Toxicol.17, 493–500.
56.
56. Fairchild, E.J. (ed.). (1977). NIOSH Registry of Toxic Effects of Chemical Substances.Rockville, MD: Tracor Jitco, Vol. II.
57.
57. CTFA. (May 1967). Submission of data by CTFA (2–11–101). 2NPPD dermal toxicity study in rabbits.*
58.
58. CTFA. (April 1967). Submission of data by CTFA (2–11–63). 2NPPD dermal toxicity study in rabbits.*
59.
59. COSMETIC, TOILETRY AND FRAGRANCE ASSOCIATION (CTFA). (February 1973). Submission of data by CTFA (2–11–102). 4NOPD dermal toxicity study in rabbits.*
60.
60. CTFA. (February 1973). Submission of data by CTFA (2–11–62). 4NOPD dermal toxicity study in rabbits.*
61.
61. Burnett, C., Goldenthal, E.I., Harris, S.B., Wazeter, F.X., Strausburg, J., Kapp, R., and Voelker, R. (1976). Teratology and percutaneous toxicity studies on hair dyes. J. Toxicol. Environ. Health1, 1027–40.
62.
62. Searle, C.E., and Jones, E.L. (1977). Effects of repeated applications of two semipermanent hair dyes to the skin of A and DBAf mice. Br. J. Cancer36, 467–78.
63.
63. Burnett, C., Jacobs, M.M., Seppala, A., and Shubik, P. (1980). Evaluation of the toxicity and carcinogenicity of hair dyes. J. Toxicol. Environ. Health6, 247–57.
64.
64. INTERNATIONAL RESEARCH AND DEVELOPMENT CORPORATION (IRDC). (February 6, 1979). Submission of data by CTFA (2–11–38). Lifetime toxicity/carcinogenesis study in rats.*
65.
65. Morikawa, F., Fujii, S., Tejima, M., Sugiyama, H., and Uzuka, M. (1976). Safety evaluation of hair cosmetics. In: Toda, K. (ed.). Biology and Disease of the Hair.Baltimore, MD: University Park Press, pp. 641–57.
66.
66. CTFA. (May 24, 1976). Submission of data by CTFA (2–11–47). Schultz, K.H. Comparable studies of sensitization of different hair dye ingredients.*
67.
67. Sheu, C.W., and Green, S. (1978). Dominant lethal studies in rats of five hair dye components: 2-nitro-p-phenylenediamine, 4-nitro-o-phenylenediamine, m-phenylenediamine, 2,4-diaminoanisole sulfate, and 2,5-diaminoanisole sulfate. Toxicol. Appl. Pharmacol.45, 219.
68.
68. Sheu, C.J., and Green, S. (1979). Dominant lethal assay of some hair-dye components in random-bred male rats. Mutat. Res.68, 85–98.
69.
69. Marks, T.A., Gupta, B.N., Ledouk, T.A., and Staples, R.E. (1981). Teratogenic evaluation of 2-nitro-p-phenylenediamine, 4-nitro-o-phenylenediamine, and 2,5-toluenediamine sulfate in the mouse. Teratology24, 253–65.
70.
70. Marks, T.A., Worthy, W.C., and Staples, R.E. (1979). Teratogenicity of 4-nitro-1,2-diaminobenzene (4NDB) and 2-nitro-1,4-diaminobenzene (2NDB) in the mouse. Teratology19, 37A–38A.
71.
71. IRDC. (November 2, 1977). Submission of data by CTFA. (2–11–37). Multigeneration reproduction study in rats.*
72.
72. BIODYNAMICS. (September 7, 1977). Submission of data by CTFA (2–11–35). Project No. 76–1667. A modified segment II teratology study of hair dyes in mice.*
73.
73. BIODYNAMICS. (1982). Submission of data by CTFA (2–11–36). Project No. 76–1666. A modified segment II teratology study of hair dyes in rabbits.*
74.
74. Ames, B.N., Kammen, H.O., and Yamasaki, E. (1975). Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc. Natl. Acad. Sci. USA72, 2423–7.
75.
75. Bruce, W.R., and Heddle, J.A. (1979). The mutagenic activity of 61 agents as determined by the micro-nucleus, Salmonella, and sperm abnormality assays. Can. J. Genet. Cytol.21, 319–33.
76.
76. Byeon, W.H., Paik, S.G., and Lee, S.Y. (1975). Mutagenicity of phenylenediamines and their derivatives. Korean J. Microbiol.13, 51–8.
77.
77. Cline, J.C., and Mcmahon, R.E. (1977). Detection of chemical mutagens, use of concentration gradient plates in a high capacity screen. Res. Commun. Chem. Pathol. Pharmacol.16, 523–33.
78.
78. De Giovanni-Donnelly, R. (1981). The comparative response of Salmonella typhimurium strains TA1538, TA98, and TA100 to various hair-dye components. Mutat. Res.91, 21–5.
79.
79. Dunkel, V.C., and Simmon, V.F. (1980). Mutagenic activity of chemicals previously tested for carcinogenicity in the National Cancer Institute bioassay program. IARC Sci. Publ.27, 283–302.
80.
80. Garner, R.C., and Nutman, C.A. (1977). Testing of some azo dyes and their reduction products for mutagenicity using Salmonella typhimurium TA 1538. Mutat. Res.44, 9–19.
81.
81. Inoue, T., Morita, K., and Kada, T. (1981). Purification and properties of a plant desmutagenic agent for the mutagenic principle of tryptophan pyrolysate. Agric. Biol. Chem.45, 345–53.
82.
82. Levin, D.E., Yamasaki, E., and Ames, B.N. (1982). A new Salmonella tester strain, TA97, for the detection of frameshift mutagens: a run of cytosines as a mutational hot-spot. Mutat. Res.94, 315–30.
83.
83. Mohn, G.R., and De Serres, F.J. (1976). On the mutagenic activity of some hair dyes. Mutat. Res.38, 116–7.
84.
84. Probst, G.S., Mcmahon, R.E., Hill, L.E., Thompson, C.Z., Epp, J.K., and Neal, S.B. (1981). Chemically induced unscheduled DNA synthesis in primary rat hepatocyte cultures: a comparison with bacterial mutagenicity using 218 compounds. Environ. Mutagen.3, 11–32.
85.
85. Searle, C.E., and Harnden, D.G. (1975). Tests of two hair colourants for carcinogenicity by repeated application to mouse skin. Br. J. Cancer32, 251.
86.
86. Shahin, M.M., and Von Borstel, R.C. (1976). Comparative studies of six compounds in Saccharomyces cerevisiae and Salmonella typhimurium reversion studies. Mutat. Res.38, 379–80.
87.
87. Shahin, M.M., and Von Borstel, R.C. (1978). Comparison of mutation induction in reversion systems of Saccharomyces cerevisiae and Salmonella typhimurium. Mutat. Res.53, 1–10.
88.
88. Yoshikawa, K., Uchino, H., and Kurata, H. (1976). Studies on the mutagenicity of hair dye. Eisei Shikensho Hokoku94, 28–32.
89.
89. Yoshikawa, K., Uchino, H., Tateno, N., and Kurata, H. (1977). Mutagenic activities of the samples prepared with raw material of hair dye. Eisei Shikensho Hokoku95, 15–24.
90.
90. De Serres, F.J., and Shebly, M.D. (1979). Recommendations on data production and analysis using the Salmonella/microsome-mutagenicity assay. Mutat. Res.64, 159–65.
91.
91. Aeschbacher, H.U., and Ruch, E. (1982). Urine-mediated Ames test: interactions. Mutat. Res.103, 127–31.
92.
92. Benigni, R., Bignami, M., Carere, A., Conti, G., Conti, L., Crebelli, R., Dogliotti, E., Gualandi, G., Novelletto, A., and Ortali, V.A. (1979). Mutational studies with diquat and paraquat in vitro. Mutat. Res.68, 183–93.
93.
93. Coleman, N., Gardner, A., and Herbert, V. (1979). Nonmutagenicity of gossypol in the Salmonella/mammalian-microsome plate test. Environ. Mutagen.1, 315–20.
94.
94. Summer, K., and Goeggelmann, W. (1980). 1-Chloro-2,4-dinitrobenzene depletes glutathione in rat skin and is mutagenic in Salmonella typhimurium. Mutat. Res.77, 91–3.
95.
95. Summer, K., and Goeggelmann, W. (1980). Mutagenicity of 1-fluoro-2,4-dinitrobenzene is affected by bacterial glutathione. Mutat. Res.70, 173–8.
96.
96. Zeiger, E., Pagano, D.A., and Robertson, I.G. (1981). A rapid and simple scheme for confirmation of Salmonella tester strain phenotype. Environ. Mutagen.3, 205–9.
97.
97. Searle, C.E., Harnden, D.G., Venitt, S., and Gyde, O.H.B. (1975). Carcinogenicity and mutagenicity tests of some hair colorants and constituents. Nature255, 506–7.
98.
98. Venitt, S., and Searle, C.E. (1976). Mutagenicity and possible carcinogenicity of hair colorants and constituents. In: International Agency for Research on Cancer, IARC Scientific Publications No. 13. Lyon, France: INSERM Symposia Series, Vol. 52, pp. 263–72.
99.
99. Burnett, C.M., Fuchs, C.M., and Corbett, J.F. (1979). Mutagenicity studies on urine concentrates from female users of dark hair color products. Drug Chem. Toxicol.2, 283–93.
100.
100. CTFA. (January 31, 1983). Summary of cosmetic ingredient safety analysis on 2-nitro-p-phenylenediamine and 4-nitro-o-phenylenediamine.*
101.
101. Mcmahon, R.E., Cline, J.C., and Thompson, C.Z. (1979). Assay of 855 test chemicals in ten tester strains using a new modification of the Ames test for bacterial mutagens. Cancer Res.39, 682–92.
102.
102. Venitt, S. (1978). Mutagenicity of hair dyes: some more evidence and the problems of its interpretation. Mutat. Res.53, 278–9.
103.
103. Tweats, D.J., Green, M.H.L., and Muriel, W.J. (1981). A differential killing assay for mutagens and carcinogens based on an improved repair-deficient strain of Escherichia coli. Carcinogenesis2, 189–94.
104.
104. Venitt, S., and Bushell, C.T. (1975). Mutagenicity of hair colorants in bacteria: possible link with carcinogenicity. Br. J. Cancer32, 251.
105.
105. Mccarroll, N.E., Keech, B.H., and Piper, C.E. (1981). A microsuspension adaptation of the Bacillus subtilis rec assay. Environ. Mutagen.3, 607–16.
106.
106. Macgregor, J.T., and Sacks, L.E. (1979). The Bacillus subtilis multigene sporulation test: Sensitivity to known mutagens and carcinogens. Environ. Mutagen.1, 121.
107.
107. Sacks, L.E., and Macgregor, J.T. (1982). The B. subtilis multigene sporulation test for mutagens: detection of mutagens inactive in the Salmonella his reversion test. Mutat. Res.95, 191–202.
108.
108. Mayer, V.W., and Goin, C.J. (1980). Induction of mitotic recombination by certain hair-dye chemicals in Saccharomyces cerevisiae. Mutat. Res.78, 243–52.
109.
109. Ong, T. (1978). Use of the spot, plate, and suspension test systems for the detection of the mutagenicity of environmental agents and chemical carcinogens in Neurospora crassa. Mutat. Res.53, 297–308.
110.
110. Bignami, M., Carere, A., Conti, G., Conti, L., Crebelli, R., and Fabrizi, M. (1982). Evaluation of 2 different genetic markers for the detection of frameshift and missense mutagen in A. nidulans. Mutat. Res.97, 293–302.
111.
111. Palmer, K.A., Denunzio, A., and Green, S. (1976). The mutagenic assay of some hair dye components using the thymidine kinase locus of L51178Y mouse lymphoma cells. Toxicol. Appl. Pharmacol.37, 108.
112.
112. Palmer, K.A., Denunzio, A., and Green, S. (1978). The mutagenic assay of some hair dye components, using the thymidine kinase locus of L5178Y mouse lymphoma cells. J. Environ. Pathol. Toxicol.1, 87–91.
114. Blijleven, W.G.H. (1977). Mutagenicity of four hair dyes in Drosophila melanogaster. Mutat. Res.48, 181–5.
115.
115. Huang, S.L. (1977). The mutability of the Minute loci and sex-linked recessive lethals in Drosophila melanogaster. Mutat. Res.44, 145–8.
116.
116. Fahmy, M.J., and Fahmy, O.G. (1977). Mutagenicity of hair dye components relative to the carcinogen benzidine in Drosophila melanogaster. Mutat. Res.56, 31–7.
117.
117. Heddle, J.A., and Bruce, W.R. (1977). Comparison of tests for mutagenicity or carcinogenicity using assays for sperm abnormalities, formation of micronuclei, and mutations in Salmonella. Cold Spring Harbor Conf. Cell Prolif.4C, 1549–57.
118.
118. Benedict, W.F. (1976). Morphological transformation and chromosome aberrations produced by two hair dye components. Nature260, 368–9.
119.
119. Ishidate, M., and Odashima, S. (1977). Chromosome tests with 134 compounds on Chinese hamster cells in vitro–A screening for chemical carcinogens. Mutat. Res.48, 337–53.
120.
120. Ishidate, M., and Yoshikawa, K. (1980). Chromosome aberration tests with Chinese hamster cells in vitro with and without metabolic activation: a comparative study on mutagens and carcinogens. In: Further studies in the assessment of toxic actions. Arch. Toxicol. [Suppl.]4, 41–4.
121.
121. Kirkland, D.J., and Venitt, S. (1976). Cytotoxicity of hair colorant constituents. Chromosome damage induced by two nitrophenylenediamines in cultured Chinese hamster cells. Mutat. Res.40, 47–55.
122.
122. Perry, P.E., and Searle, C.E. (1977). Induction of sister chromatid exchanges in Chinese hamster cells by the hair dye constituents 2-nitro-p-phenylenediamine and 4-nitro-o-phenylenediamine. Muat. Res.56, 207–10.
123.
123. Hossack, D.J.N., and Richardson, J.C. (1977). Examination of the potential mutagenicity of hair dye constituents using the micronucleus test. Experientia33, 377–8.
124.
124. Wild, D., King, M.T., and Eckhardt, K. (1980). Cytogenetic effect of ortho-phenylenediamine in the mouse, Chinese hamster, and guinea pig and of derivatives, evaluated by the micronucleus test. Arch. Toxicol.43, 249–55.
125.
125. Griffiths, A.J.F. (1979). Neruospora prototroph selection system for studying aneuploid production. Environ. Health Perspec.31, 75–80.
126.
126. Painter, R.B., and Howard, R. (1982). The HeLa DNA synthesis inhibition test as a rapid screen for mutaenic carcinogens. Mutat. Res.92, 427–38.
127.
127. Martin, C.N., Mcdermid, A.C., and Garner, R.C. (1978). Testing of known carcinogens and noncarcinogens for their ability to induce unscheduled DNA synthesis in HeLa cells. Cancer Res.38, 2621–7.
128.
128. Probst, G.S., and Hill, L.E. (1980). Chemically induced DNA repair synthesis in primary rat hepatocytes: A correlation with bacterial mutagenicity. Ann. NY Acad. Sci.349, 405–6.
129.
129. Williams, G.M., Laspia, M.F., and Dunkel, V.C. (1982). Reliability of the hepatocyte primary culture/DNA repair test in testing of coded carcinogens and noncarcinogens. Mutat. Res.97, 359–70.
130.
130. Smith, N.S., Bishun, N.P., and Williams, D. (1976). Depression of lymphocyte transformation by two hair dye constituents. Microbios Lett.1, 205–8.
131.
131. Pienta, R.J. (1980). Transformation of Syrian hamster embryo cells by diverse chemicals and correlation with their reported carcinogenic and mutagenic activities. Chemical Mutagens: Principal Methods for Their Detection6, 175–202.
132.
132. Pienta, R.J. (1980). Evaluation and relevance of the Syrian hamster embryo cell system. Appl. Methods Oncol.3, 149–69.
133.
133. Pienta, R.J., and Kawalek, J.C. (1981). Transformation of hamster embryo cells by aromatic amines. Natl. Cancer Inst. Monogr.58, 243–51.
134.
134. Traul, K.A., Takayama, K., Kachevsky, V., Hink, R.J., and Wolff, J.S. (1981). Rapid in vitro assay for carcinogenicity of chemical substances in mammalian cells utilizing an attachment-independence endpoint. 2. Assay validation. J. Appl. Toxicol.1, 190–5.
135.
135. Yoshikura, H., Kuchino, T., and Matsushima, T. (1979). Carcinogenic chemicals enhance mouse leukemia virus infection in contact-inhibited culture: a new simple method of screening carcinogens. Cancer Lett.7, 203–8.
136.
136. CTFA. (December 17, 1981). Submission of data by CTFA (2–11–4). CTFA interoffice correspondence and letters on NCl study by two pathologists.*
137.
137. NORTH AMERICAN CONTACT DERMATITIS GROUP. (December 4, 1980). Standard screening tray, 1979 vs. 1980 summary.
138.
138. DERMA-TEST LABORATORIES (DTL). (September 22, 1982). Submission of data by CTFA. Repeated insult patch test, product: 1101–49 and 1101–52 mixed equal parts.*
139.
139. DTL. (September 22, 1982). Submission of data by CTFA. Repeated insult patch test, product: 1101–48 and 1101–52 mixed equal parts.*
140.
140. DTL. (September 22, 1982). Submission of data by CTFA. Repeated insult patch test, product: 1101–50 and 1101–52 mixed equal parts.*
141.
141. Hindson, C. (1975). o-Nitro-paraphenylenediamine in hair dye–An unusual dental hazard. Contact Dermatitis1, 333.
142.
142. Anthony, H.M., and Thomas, G.M. (1970). Tumors of the urinary bladder: An analysis of the occupations of 1030 patients in Leeds, England. J. Natl. Cancer Inst.45, 879–98.
143.
143. Cole, P., Hoover, R., and Friedall, C.H. (1972). Occupation and cancer of the lower urinary tract. Cancer29, 1250–60.
144.
144. Dunham, L.J., Rabson, A.S., Stewart, H.L., Frank, A.S., and Young, J.L. (1968). Rate, interview, and pathology study of cancer of the urinary bladder in New Orleans, LA. J. Natl. Cancer Inst.41, 683–709.
145.
145. Wynder, E.L., Onderdonk, J., and Mantel, N. (1963). An epidemiological investigation of cancer of the bladder. Cancer16, 1388–407.
146.
146. Garfinkel, J., Selvin, S., and Brown, S.M. (1977). Possible increased risk of lung cancer among beauticians. J. Natl. Cancer Inst.58, 141–3.
147.
147. Menck, H.R., Pike, M.C., Henderson, B.E., and Jing, J.S. (1977). Lung cancer risk among beauticians and other female workers. J. Natl. Cancer Inst.59, 1423–5.
148.
148. Jain, M., Morgan, R.W., and Elinson, L. (1977). Hair dyes and bladder cancer. Can. Med. Assoc. J.117, 1131–3.
149.
149. Hennekens, C.H., Speizer, F.E., Rosner, B., Bain, C.J., Belanger, C., and Peto, R. (1979). Use of permanent hair dyes and cancer among registered nurses. Lancet1:1390–3.
150.
150. Kinlen, L.J., Harris, R., Garrod, A., and Rodriguez, K. (1977). Use of hair dyes by patients with breast cancer: A case-control study. Br. Med. J.2, 366–8.
151.
151. Nasca, P.C., Lawrence, C.E., Greenwald, P., Chorost, S., Arbuckle, J.T., and Paulson, A. (1979). Relationship of hair dye use, benign breast disease, and breast cancer. J. Natl. Cancer Inst.64, 23–8.
152.
152. Shafer, N., and Shafer, R.W. (1976). Potential of carcinogenic effects of hair dyes. NY State J. Med.76, 394–6.
153.
153. Shore, R.E., Pasternack, B.S., Thiessen, E.U., Sadow, M., Forbes, R., and Albert, R.E. (1979). A case-control study of hair dye use and breast cancer. J. Natl. Cancer Inst.62, 277–83.
154.
154. Wynder, E.L., and Goodman, M. (1983). Epidemiology of breast cancer and hair dyes. J. Natl. Cancer Inst.71, ???.
155.
155. FEDERAL REGISTER. (October 16, 1979). Cosmetic product warning statements coal tar hair dyes containing 4-methoxy-m-phenylenediamine (2,4-diaminoanisole) or 4-methoxy-m-phenylenediamine (2,4,-diaminoanisole sulfate). 44, 59509–22.
156.
156. Clemmesen, J. (1981). Epidemiological studies into the possible carcinogenicity of hair dyes. Mutat. Res.87, 65–79. *Available upon request: Administrator, Cosmetic Ingredient Review, 1110 Vermont Ave., NW, Suite 810, Washington, DC 20005.
