title: Bioassay of 4-amino-2-nitrophenol for possible carcinogenicity.
abstract: A bioassay of 4-amino-2-nitrophenol for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered 4-amino-2-nitrophenol at one of two doses, either 1,250 or 2,500 ppm, for 103 weeks. Matched controls consisted of groups of 20 untreated rats and 20 untreated mice of each sex. All dosed and matched-control groups of each species and sex were killed at 105 weeks. Mean body weights of dosed rats of each sex were not appreciably affected by administration of the 4-amino-2-nitrophenol, and mean body weights of dosed mice of each sex were only slightly lower than those of corresponding matched controls. Survival of neither rats nor mice was affected by the test chemical, and sufficient numbers of animals in dosed and control groups were at risk for the development of late-appearing tumors. Since both male and female mice receiving 4-amino-2-nitrophenol had little or no depression in mean weights and their survival was comparable to that of controls, they may have been able to tolerate a higher dose. In rats, transitional-cell carcinomas of the urinary bladder showed a dose-related trend in the males (P<0.001) and occurred at a significantly higher incidence (P=0.018) in the high-dose males than in the matched-control males (controls 0/15, low-dose 0/46, high-dose 11/39 [28%]). Carcinomas of the bladder also occurred in one low-dose female and two high-dose females, but in none of the control females. Transitional-cell papillomas of the bladder occurred in two additional high-dose males, and transitional-cell hyperplasia of the bladder occurred in four additional high-dose males, but neither lesion occurred in control males. No tumors of the bladder were found among 220 male and 220 female historical-control rats at this laboratory. In mice, no tumors occurred in dosed groups of males or females at incidences that were significantly higher than those in the corresponding matched-control groups. Deposition of pigment occurred in the lamina propria of the small intestine in at least 91% of the animals in the dosed groups of rats and in at least 89% of the animals in the dosed groups of mice, but in none of the control groups of either species. It is concluded that under the conditions of the bioassay, 4-amino-2-nitrophenol was carcinogenic for male Fischer 344 rats, inducing transitional-cell carcinomas of the urinary bladder; the transitional-cell carcinomas of the urinary bladder observed in three dosed female rats may also have been associated with administration of the 4-amino-2-nitrophenol. The test chemical was not carcinogenic for male or female B6C3F1 mice at the doses tested.