Final Report on the Safety Assessment of 4-Nitro-m-Phenylenediamine

Abstract

4-Nitro-m-Phenylenediamine is a coal tar cosmetic used at concentrations of ≤0.1 %. In an acute oral toxicity study involving mice, the LD₅₀ was 0.5 g/kg. 4-Nitro-m-Phenylenediamine was mutagenic in the chromosome aberrations assay and in the preincubation assay, using strains TA97, TA98, and TA 1537 of Salmonella typhimurium. The safety of use of 4-Nitro-m-Phenylenediamine in cosmetic products has not been documented and substantiated. The needed safety test data include: methods of production, ultraviolet absorption spectrum, impurities, skin absorption data, adequately performed skin irritation and sensitization studies, and dermal toxicity. It cannot be concluded that this ingredient is safe for use in cosmetic products until the cited safety data have been obtained and evaluated.

References

Anthony, H.M. and Thomas, G.M. (1970). Tumors of the urinary bladder: an analysis of the occupations of 1,030 patients in Leeds, England. J. Natl. Cancer Inst. 45:879–898.

Clemmesen, J. (1981). Epidemiological studies into the possible carcinogenicity of hair dyes. Mutat. Res. 87:65–79.

Code Of Federal Regulations (Cfr). (Revised as of April 1, 1984). Title 21 Part 720.4. Information requested about cosmetic products. Washington, D.C.: U.S. Government Printing Office.

Cole, P. , Hoover, R. , and Friedall, C.H. (1972). Occupation and cancer of the lower urinary tract. Cancer 29:1250–1260.

Corbett, J.F. and Menkart, J. (1973). Hair coloring. Cutis 12:190–197.

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.

Elder, R.L. (Ed.). (1985a). Final report on the safety assessment of p-phenylenediamine. J. Am. Coll. Toxicol. 4(3):203–266.

Elder, R.L. (Ed.). (1985b). Final report on the safety assessment of 2-nitro-p-phenylenediamine and 4-nitro-o-phenylenediamine. J. Am. Coll. Toxicol. 4(3):161–202.

Environmental Protection Agency (Epa). (1982). Phenylenediamines: response to interagency testing committee. Fed. Reg. 47(5):979.

10.

Estrin, N.F. , Crosley, P.A. , and Haynes, C.R. (1982). Cosmetic Ingredient Dictionary. Washington, D.C.: CTFA, p. 180.

11.

Federal Register. (Oct. 16, 1979). Cosmetic Product Warning Statements: coal tar hair dyes containing 4-methoxy-m-phenylenediamine (2,4-diaminoanisole) or 4-methoxy-m-phenylenediamine sulfate (2,4-diaminoanisole sulfate). 44(201): 59509–10.

12.

Food And Drug Administration (Fda). (1989). Cosmetic product formulation data. FDA computer printout.

13.

Fda. (November 18, 1991). Cosmetic product formulation data. FDA computer printout.

14.

Garfinkel, J. , Selvin, S. , and Brown, S.M. (1977). Possible increased risk of lung cancer among beauticians. J. Natl. Cancer Inst. 58:141–143.

15.

Green, A. , Willet, W.C. , Colditz, G.A. , Stampfer, M.J. , Bain, C. , Rosner, B. , Hennekens, C.H. , and Speizer, F.E. (1987). Use of permanent hair dyes and risk of breast cancer. J. Natl. Cancer Inst. 79(2):253–257.

16.

Haworth, S. , Lawlor, T. , Mortelmans, K. , Speck, W. , and Zeiger, E. (1983). Salmonella mutagenicity results for 250 chemicals. Environ. Mutagen. 5(Suppl 1):3–142.

17.

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. Lancet 1:1390–1393.

18.

International Agency For Research On Cancer (Iarc). (1978). Evaluation of the carcinogenic risk of chemicals to humans. Lyon, France: IARC 16:51–62.

19.

Jain, M. , Morgan, R.W. , and Elinson, L. (1977). Hair dyes and bladder cancer. Can. Med. Assoc. J. 117:1131–1133.

20.

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. 2:366–368.

21.

Koenig, K. , Pasternack, B.S. , Shore, R.E. , and Strat, P. (1991). Hair dye use and breast cancer: A case-controlled study among screening participants. Am. J. Epidemiol. 133:985–995.

22.

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. 59:1423–1425.

23.

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. 64:23–28.

24.

National Toxicology Program (Ntp). (1989). NTP unpublished results. In vitro cytogenetics assays.

25.

Nikitakis, J.M. (1988). Cosmetic Ingredient Handbook. Washington, D.C.: CTFA, p. 271.

26.

Registry Of Toxic Effects Of Chemical Substances (Rtecs). (1990). (Updated on 4–30–90). National Library of Medicine computer printout. Data on 4-nitro-m-phenylenediamine.

27.

Shafer, N. and Shafer, R.W. (1976). Potential of carcinogenic effects of hair dyes. N.Y. State J. Med. 76:394–396.

28.

Shore, R.E. , Pasternack, B.S. , Thiessen, E.U. , Sadow, M. , Forbes, R. , and Albert, R.E. (1979). A case-controlled study of hair dye use and breast cancer. J. Natl. Cancer Inst. 62:277–283.

29.

Wynder, E.L. and Goodman, M. (1983). Epidemiology of breast cancer and hair dyes. J. Natal. Cancer Inst. 71:481–488.

30.

Wynder, E.L. , Onderdonk, J. , and Mantel, N. (1963). An epidemiological investigation of cancer of the bladder. Cancer 16:1388–1407.

31.

Zeiger, E. , Anderson, B. , Haworth, S. , Lawlor, T. , and Mortelmans, K. (1988). Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals. Environ. Mol. Mutagen. 11(Suppl. 12):1–157.