Bioassay of N-nitrosodiphenylamine for possible carcinogenicity.

Abstract

A bioassay of N-nitrosodiphenylamine for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered N-nitrosodiphenylamine at one of two doses, either 1,000 or 4,000 ppm, for 100 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of administration of the test chemical. Groups of 50 male mice were administered N-nitrosodiphenylamine at one of two doses, either 10,000 or 20,000 ppm, for 101 weeks. Groups of 50 female mice were administered the test chemical at one of two doses, initially 5,000 or 10,000 ppm, for 38 weeks. Because of excessive depression in the amount of mean body weight gained in the dosed groups, the doses for the females were then reduced to 1,000 and 4,000 ppm, respectively, and administration at the lowered doses was continued for 60 weeks. The time-weighted average doses for the female mice were either 2,315 or 5,741 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at the end of administration of the test chemical. Mean body weights of dosed rats and mice of each sex were lower than those of corresponding controls, and were dose related throughout the bioassay, except for those of female rats during the first part of the bioassay. Mortality was dose related in the female rats, but was not affected when the test chemical was administered to the male rats or the male or female mice. Survival at the end of the bioassay was 64% or greater in the dosed and control groups of rats and mice of each sex, and sufficient numbers of animals were at risk in all groups for the development of late-appearing tumors. Transitional-cell carcinomas of the urinary bladder occurred at incidences that were dose related (P