Bioassay of 4-chloro-o-toluidine hydrochloride for possible carcinogenicity.
A bioassay of 4-chloro-o-toluidine hydrochloride 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 4-chloro-o-toluidine in the diet at one of two doses, either 1,250 or 5,000 ppm, for 107 weeks. Groups of 50 mice of each sex were administered the test chemical in the diet at one of two doses, either 3,750 or 15,000 ppm for the males and either 1,250 or 5,000 ppm for females, for 99 weeks, except for the high dose females (92 weeks). Matched controls consisted of 20 untreated rats and 20 untreated mice of each sex. All surviving animals were killed at the end of administration of the test chemical. Mean body weights of the high-dose rats and the low- and high-dose mice of each sex were lower than those of corresponding controls, and those of the mice were dose related. Mortality was not significantly affected by administration of the test chemical to rats of either sex and survival was 75% or greater at the end of the study in dosed and control groups. Sufficient numbers of rats were at risk for the development of late-appearing tumors. In mice, mortality was dose related for each sex. In rats no tumors occurred at incidences which could clearly be related to administration of the test chemical. In both male and female mice, hemangiosarcomas occurred at incidences that were dose related (P</= 0.001), and in direct comparisons the incidences in the high-dose males and the low-and high-dose females were significantly higher (P<0.001) than those in the corresponding controls (males: controls 0/20; low-dose 3/50; high-dose 37/50; females: controls 0/18; low-dose 40/49, high-dose 39/50). The combined incidences of hemangiosarcomas and hemangiomas also were dose related and were significantly higher in the dosed groups of male and female mice than in the corresponding controls. There was a high incidence of hemosiderin deposit in the renal tubular epithelium, particularly in mice with hemangiosarcomas. It is concluded that under the conditions of this bioassay, 4-chloro-o-toluidine hydrochloride was not carcinogenic for F344 rats but was carcinogenic for B6C3F1 mice, including hemangiosarcomas and hemangiomas in both males and females. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Positive Female Mice: Positive Synonym: 2-amino-4-chlorotoluene hydrochloride