Lifetime carcinogenicity study of 1- and 2-naphthylamine in dogs

Groups of male and female beagle dogs were given daily doses of 400 mg of various mixtures of naphthylamines for up to 109 months. Survivors were killed at 128 months. A variety of pathological conditions was diagnosed, but the only effect related to treatment was the induction of bladder neoplasms. All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months. Two of 8 dogs receiving 6% 2-naphthylamine in 1-naphthylamine developed early carcinoma and 2/8 dogs receiving 0.5% 2-naphthylamine in 1-naphthylamine developed haemangioma of the bladder. Some of the dogs receiving 1-naphthylamine (total dose 950 g) and the controls had focal cystitis or hyperplasia, but no neoplasia of the bladder. These results confirm the carcinogenicity of 2-naphthylamine to dogs. No carcinogenic effect of 1-naphthylamine was observed, indicating that it is at least 200 times less potent as a carcinogen than 2-naphthylamine. The incidence of bladder cancer in dogs fed mixtures of both naphthylamines explains why previous experimental and epidemiological studies of impure 1-naphthylamine have revealed carcinogenicity.