p-Anisidine hydrochloride, the hydrochloride salt of an aromatic dye intermediate, was selected for bioassay by the National Cancer Institute because of the increased bladder cancer incidence noted among workers in the dye manufacturing industry.
A bioassay for possible carcinogenicity of p-anisidine hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. p-Anisidine hydrochloride was administered in the feed, at either of two concentrations, to groups of 55 male and 55 female animals of each species. Fifty-five animals of each sex and species were placed on test as controls. The high and low dietary concentrations of p-anisidine hydrochloride were, respectively, 0.6 and 0.3 percent for rats and 1.0 and 0.5 percent for mice. The compound was administered in the diet for 103 weeks, followed by an observation period of 2 to 3 weeks for rats and 2 weeks for mice.
There were no significant positive associations for either species between the concentration of p-anisidine hydrochloride administered and mortality. In addition, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors.
In male rats there were significant associations between compound administration and the incidences of both squamous-cell carcinomas of the skin and alveolar/bronchiolar adenomas. None of the Fischer exact comparisons, however, supported these findings. When those males having adenomas NOS or carcinomas NOS of the preputial gland were combined and the resulting incidences statistically analyzed, the only test providing a significant result was the Fisher exact comparison of the low dose to the control. There were no significant positive associations between the administration of p-anisidine hydrochloride and the incidence of any tumor in mice of either sex.
Although, under the conditions of this bioassay, there appeared to be an association between chemical administration and the increased incidence of preputial gland tumors in low dose male rats, the evidence was insufficient to establish the carcinogenicity of p-anisidine hydrochloride in Fischer 344 rats. The compound was not carcinogenic in B6C3F1 mice.