Bioassay of chloramben for possible carcinogenicity.
A bioassay of technical-grade chloramben for possible carcinogenicity was conducted by administering the test material in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats and 50 mice of both sexes were administered chloramben at one of two doses, either 10,000 or 20,000 ppm. The rats were treated for 80 weeks, then observed for 32 or 33 weeks; the mice were treated for 80 weeks, then observed for 11 or 12 weeks. Matched controls consisted of groups of 10 untreated rats and 10 untreated mice of each sex; pooled controls, used for statistical evaluation, consisted of these matched controls combined with 75 untreated male and 75 untreated female rats or 70 untreated male and 70 untreated female mice from similarly performed bioassays of six other test chemicals. Surviving rats were killed at 112 or 113 weeks; surviving mice were killed at 91 or 92 weeks. Body weights and mortality of the treated animals were not markedly affected by chloramben under the conditions of the bioassay. The various clinical signs observed were common to both treated and control groups. In male rats, hemangiomas occurred at a significantly higher incidence in the low-dose animals than in the pooled controls (controls 0/73, low-dose 5/48, P=0.009). This lesion was not considered to be related to the administration of chloramben, since the tumor did not occur at a significantly higher incidence in the high-dose group than in the pooled-control group, and the incidences did not show a significant dose-related trend. In both male and female mice, the incidences of hepatocellular carcinoma showed significant dose-related trends using pooled controls (for females: controls 9/69, low dose 16/48, high-dose 14/48, P=0.029; for females controls 2/67, low-dose 7/48, high-dose 10/50, P=0.004). Direct comparisons showed significantly higher incidences of the tumor in the low-dose males (P=0.008) and in the high-dose females (P=0.003) than in the pooled controls. Probability levels of P=0.028 in high-dose males and P=0.027 in low-dose females were attained. In male mice, however, the incidence of hepatocellular carcinoma was considered to be only marginally associated with the administration of chloramben because of the variations in the spontaneous incidence of this lesion in male mice encountered at this laboratory. In conclusion, under the conditions of this bioassay, there were no tumors in Osborne-Mendel rats that were significantly related to administration of the chemical. In B6C3F1 female mice, chloramben was carcinogenic, producing hepatocellular carcinomas in treated animals.