For definition of Groups, see Preamble Evaluation.
Supplement 7: (1987) (p. 261)
CAS No.:
A. Evidence for carcinogenicity to humans (sufficient)
Case reports and epidemiological studies conducted independently in the 1950s and 1960s showed that occupational exposure to 2-naphthylamine, either alone or as an impurity in other compounds, is causally associated with the occurrence of bladder cancer [ref: 1].
Two studies in the USA examined cancer incidence and mortality in a group of chemical workers exposed mainly to 2-naphthylamine. In one, a remarkable and significantly increased incidence of bladder cancer was found (13 observed, 3.3 expected), which was not explained by smoking habits [ref: 2]. Investigation of mortality failed to pinpoint this increased risk and suggested an excess of oesophageal cancer, which, however, was not considered to be associated with the occupational exposure [ref: 3]. Two reports on one occupational population at a dyestuffs plant in Italy documented a very high bladder cancer risk linked specifically to 2-naphthylamine production (6 deaths observed, 0.04 expected) and a clear exposure-response relationship of the risk to exposures in the plant [ref: 4,5]. Incidence studies from Japan dealing with exposure to both 2-naphthylamine and benzidine showed apparently increased risks of cancer of the urinary tract and bladder and, possibly, an increased occurrence of second primary cancers at several sites, including the liver [ref: 6-8]. Case reports and ecological studies also documented the relationship between exposure to 2-naphthylamine, as well as to benzidine, and bladder cancer risk [ref: 9,10]. 2-Naphthylamine was most probably involved in the exposure to aryl amines reported in a UK study as producing a significantly increased bladder cancer risk, which was not accounted for by smoking habits [ref: 11].
B. Evidence for carcinogenicity to animals (sufficient)
2-Naphthylamine was tested for carcinogenicity by oral administration in many animal species and by the mouse-lung adenoma bioassay. Following its oral administration, it induced bladder neoplasms in hamsters [ref: 1], dogs [ref: 1,12-14] and nonhuman primates [ref: 1], and liver tumours in mice [ref: 1]. A low incidence of bladder carcinomas was observed in rats after its oral administration [ref: 15]. In a lung adenoma bioassay in mice, 2-naphthylamine produced positive results [ref: 16].
C. Other relevant data
No data were available on the genetic and related effects of 2-naphthylamine in humans.
Mice and rabbits treated with 2-naphthylamine had increased incidences of sister chromatid exchanges; micronuclei were not induced in bone-marrow cells of mice treated in vivo. 2-Naphthylamine was mutagenic in the mouse spot test and induced DNA strand breaks in hepatocytes of treated rats. It formed DNA adducts in bladder and liver cells of dogs in vivo. It induced unscheduled DNA synthesis in human cells in vitro and chromosomal aberrations, sister chromatid exchanges, DNA strand breaks and unscheduled DNA synthesis in rodent cells in vitro. Equivocal results were obtained for mutation, but it caused morphological transformation in Syrian hamster embryo and virus-infected rat cells. 2-Naphthylamine induced aneuploidy in Drosophila, but equivocal results were found for sex-linked recessive lethal mutations. It caused aneuploidy, mutation and mitotic recombination in yeast and was mutagenic to plants and bacteria [ref: 17].
Overall evaluation
2-Naphthylamine is carcinogenic to humans (Group 1).
For definition of the italicized terms, see Preamble Evaluation.
Also see previous evaluation: Vol. 4 (1974)
References
1. IARC Monographs, 4, 97-111, 1974
2. Schulte, P.A., Ringen, K., Hemstreet, G.P., Altekruse, E.B., Gullen, W.H., Patton, M.G., Allsbrook, W.C., Jr, Crosby, J.H., West, S.S., Witherington, R., Koss, L., Bales, C.E., Tillet, D., Rooks, S.C.F., Stern, F., Stringer, W., Schmidt, V.A. & Brubaker, M.M. (1985) Risk assessment of a cohort exposed to aromatic amines. Initial results. J. occup. Med., 27, 115-121
3. Stern, F.B., Murthy, L.I., Beaumont, J.J., Schulte, P.A. & Halperin, W.E. (1985) Notification and risk assessment for bladder cancer of a cohort exposed to aromatic amines. III. Mortality among workers exposed to aromatic amines in the last beta-naphthylamine manufacturing facility in the United States. J. occup. Med., 27, 495-500
4. Rubino, G.F., Scansetti, G., Piolatto, G. & Pira, E. (1982) The carcinogenic effect of aromatic amines: an epidemiological study on the role of o-toluidine and 4,4'-methylene bis(2-methylaniline) in inducing bladder cancer in man. Environ. Res., 27, 241-254
5. Decarli, A., Peto, J., Piolatto, G. & La Vecchia, C. (1985) Bladder cancer mortality of workers exposed to aromatic amines: analysis of models of carcinogenesis. Br. J. Cancer, 51, 707-712
6. Tsuchiya, K., Okubo, T. & Ishizu, S. (1975) An epidemiological study of occupational bladder tumours in the dye industry of Japan. Br. J. ind. Med., 32, 203-209
7. Nakamura, J., Takamatsu, M., Doi, J., Ohkawa, T., Fujinaga, T., Ebisuno, S. & Sone, M. (1980) Clinical study on the occupational urinary tract tumor in Wakayama. Jpn. J. Urol., 71, 945-951
8. Morinaga, K., Oshima, A. & Hara, I. (1982) Multiple primary cancers following exposure to benzidine and beta-naphthylamine. Am. J. ind. Med., 3, 243-246
9. Budnick, L.D., Sokal, D.C., Falk, H., Logue, J.N. & Fox, J.M. (1984) Cancer and birth defects near the Drake Superfund site, Pennsylvania. Arch. environ. Health, 39, 409-413
10. Segnan, N. & Tanturri, G. (1976) A study on the geographical pathology of laryngeal, bladder and children cancer in the Province of Turin (Ital.). Tumori, 62, 377-386
11. Boyko, R.W., Cartwright, R.A., Chir, B. & Glashan, R.W. (1985) Bladder cancer in dye manufacturing workers. J. occup. Med., 27, 799-803
12. Romanenko, A.M. & Martynenko, A.G. (1972) Morphological peculiarities of vesical tumours induced by beta-naphthylamine in dogs (Russ.). Vopr. Onkol., 18, 70-75
13. Radomski, J.L., Krischer, C. & Krischer, K.N. (1978) Histologic and histochemical preneoplastic changes in the bladder mucosae of dogs given 2-naphthylamine. J. natl Cancer Inst., 60, 327-333
14. Purchase, I.F.H., Kalinowski, A.E., Ishmael, J., Wilson, J., Gore, C.W. & Chart, I.S. (1981) Lifetime carcinogenicity study of 1- and 2-naphthylamine in dogs. Br. J. Cancer, 44, 892-901
15. Hicks, R.M., Wright, R. & Wakefield, J.St J. (1982) The induction of rat bladder cancer by 2-naphthylamine. Br. J. Cancer, 46, 646-661
16. Theiss, J.C., Shimkin, M.B. & Weisburger, E.K. (1981) Pulmonary adenoma response of strain A mice to sulfonic acid derivaties of 1- and 2-naphthylamines. J. natl Cancer Inst., 67, 1299-1302
17. IARC Monographs, Suppl. 6, 410-414, 1987
Synonyms
See Also:
Toxicological Abbreviations
Naphthylamine, 2- (IARC Summary & Evaluation, Volume 4, 1974)