title: Bioassay of o-anisidine hydrochloride for possible carcinogenicity.
abstract: A bioassay of o-anisidine hydrochloride for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 55 rats of each sex and 55 mice of each sex were administered o-anisidine hydrochloride at one of the following doses, either 5,000 or 10,000 ppm for rats and either 2,500 or 5,000 ppm for mice, for 103 weeks, then observed for 1 or 2 additional weeks. Controls consisted of groups of 55 untreated rats of each sex and 55 untreated mice of each sex. All surviving rats were killed at 103-107 weeks, and all surviving mice at 104 or 105 weeks. Mean body weights of the dosed male and female rats and mice were lower than those of the corresponding controls throughout the bioassay. Bloody exudates and stained fur in the urogenital area were noted in many dosed animals. Sufficient numbers of animals were at risk in the mice, but not in the rats, for development of late-appearing tumors; however, survival in the rats was 80% or more at week 52. Transitional-cell carcinomas or papillomas of the urinary bladder occurred at statistically significant incidences (P<0.001) in the low- and high-dose groups of rats (males: controls 0/51, low-dose 52/54, high-dose 52/52; females: controls 0/49, low-dose 1/51, high-dose 22/50); the incidences also had significant dose-related trends (P<0.001) in both species. These lesions were observed as early as week 36 in female rats, week 40 in male rats, and week 45 in male mice. Transitional-cell carcinomas of the pelvis of the kidney occurred with a significant dose-related trend (P=0.005) in the male rats, and the incidence in the high-dose group was significantly higher (P=0.006) than that in the control group (controls 0/53, low-dose 3/55, high-dose 7/53); all rats having this tumor also has a transitional-cell carcinoma of the urinary bladder. Only one animal in the control groups of rats or mice had any tumor of the urinary system (a transitional-cell papilloma of the pelvis of the kidney in a male mouse). Follicular-cell tumors of the thyroid (carcinomas, cystadenocarcinomas, adenomas, cystadenomas, and papillary cystadenomas) occurred at statistically significant incidences (P</= 0.005) in low- and high-dose groups of male rats (controls 0/53, low-dose 7/40, high-dose 6/40); the incidences also had a dose-related trend (P=0.009). These tumors did not occur at significant incidences in dosed groups of female rats. It is concluded that under the conditions of this bioassay, o-anisidine hydrochloride was carcinogenic for Fischer 344 rats and B6C3F1 mice, inducing transitional-cell carcinomas or papillomas of the bladder in both rats and mice and in both sexes of each species, transitional-cell carcinomas of the pelvis of the kidney in male rats, and follicular-cell tumors of the thyroid in male rats.