Carcinogenesis bioassay in rats and mice fed diets containing 2-biphenylamine hydrochloride

Diets containing 0.1 or 0.3% 2-biphenylamine hydrochloride were fed to groups of 50 Fischer 344 rats and 50 B6C3F1 mice of each sex for 104-106 weeks. Mean body weights of high-dose rats of both sexes and of low-dose male rats were slightly lower than those of controls. No significant differences in survival times were observed between dosed and control groups. In dosed male rats there was a compound-related increased incidence of kidneys with inflammatory cells and interstitial fibrosis. No tumors in dosed rats were associated with the chemical. Mean body weights of high-dose male mice were slightly lower than those of controls, and survival of high-dose male mice was also significantly (P less than 0.01) reduced relative to controls. Hemangiosarcoma of the circulatory system occurred in female mice with a statistically significant (P less than 0.001) positive trend. The observed incidences of hemangiosarcoma were 0/49 (0%), 1/50 (2%), and 7/50 (14%) in controls, low- and high-dose groups, respectively. In individual group comparisons, the incidence in the high-dose group was significantly (P less than 0.01) higher than that in the controls. The hemangiosarcoma seen in female mice were quite rare with only 6/816 (0.7%) previously seen in controls at the same laboratory and no more than 3 in any group of 50. Hemangiosarcoma also occurred in male mice with a statistically significant positive trend (P = 0.04 by a life table test), with incidences of 0/50 (0%), 2/50 (4%), and 3/50 (6%), in control, low-dose and high-dose groups, respectively. The development of hemangiosarcoma in the high-dose male mice might have been curtailed by the significantly reduced survival time in this group.