3-Chloro-p-toluidine, a dye intermediate and avicide, was selected for bioassay by the National Cancer Institute because of the increased incidence of bladder cancer observed among workers in the dye manufacturing industry. Aromatic amines, of which 3-chloro-p-toluidine is one example, are among several classes of chemicals believed to contribute to this increased cancer risk.
A bioassay for the possible carcinogenicity of 3-chloro-p-toluidine was conducted using Fischer 344 rats and B6C3F1 mice. 3-Chloro-p-toluidine was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The time-weighted average dietary concentrations of 3-chloro-p-toluidine administered to rats of both sexes were 3,269 and 1,635 ppm for the high and low dose groups, respectively. The high and low dietary concentrations of 3-chloro-p-toluidine administered to mice were, respectively, 1,200 and 600 ppm for males and 600 and 300 ppm for females. The compound was administered in the diet for 78 weeks, followed by an observation period of 24 weeks for high dose male rats, 25 weeks for all other dosed rats, and 12 weeks for mice.
There were no significant positive associations between the concentrations of 3-chloro-p-toluidine administered and mortality in either species. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, relative to controls, was observed in high dose rats and mice of both sexes, indicating that the concentrations administered to these animals may have approximated the maximum tolerated dosages. The unusual incidences of nonneoplastic spleen and liver lesions in high dose rats supports this assumption.
Under the conditions of this bioassay there was no convincing evidence for the carcinogenicity of 3-chloro-p-toluidine in Fischer 344 rats or B6C3F1 mice.