Determining the Potential of Aromatic Amines to Induce Cancer of the Urinary Bladder

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Abstract
Aromatic amines have been associated with the induction of cancer of the urinary bladder. Commercial production started over 100 years ago in Europe, with the synthesis of a mauve pigment from aniline. The discovery of other pigments by combining aniline with various chemicals initiated the aniline dye industry. By the turn of the century, a correlation between working in the dyestuff industry and the development of bladder cancer was established. Initially thought to be the result of exposure to aniline, various investigators identified benzidine, beta-naphthylamine, and 4-aminobipheny 1 as the causative agents. Evaluations of various aromatic amines in rats, mice, guinea pigs, rabbits, dogs, and monkeys showed significant species differences, with the dog and monkey being the most sensitive species. Several laboratories related these species differences to differences in the respective routes by which the various species metabolized aromatic amines. Excellent correspondence was shown between metabolic activation of benzidine, 4-aminobiphenyl, and beta-naphthylamine in dogs and primates and the induction of bladder cancer. Rodents were shown to be unresponsive to human bladder carcinogens. The need to use data developed in the most sensitive species, the dog, is essential to accurately predict the carcinogenic potential of aromatic amines.