Bioassay of lindane for possible carcinogenicity.
A bioassay for possible carcinogenicity of lindane was conducted by administering the test chemical in the diet to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered lindane at one of two doses for 80 weeks, then observed for 29-30 weeks. Time-weighted average doses for males were 236 or 472 ppm; those for females were 135 or 270 ppm. Matched controls consisted of groups of 10 untreated rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched-control groups combined with 45 untreated male and 45 untreated female rats from similar bioassays of four other test chemicals. All surviving rats were killed at 108-110 weeks. Groups of 50 mice of each sex were administered lindane at one of two doses, either 80 or 160 ppm, for 80 weeks, then observed for an additional 10-11 weeks. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls, used for statistical evaluation, consisted of the matched-control groups combined with 40 untreated male and 40 untreated female mice from similar bioassays of four other test chemicals. All surviving mice were killed at 90-91 weeks. Neither the mean body weights of rats nor those of mice showed consistent effects from the administration of lindane. The physical condition of the surviving treated mice deteriorated during the final 6 weeks on study. Except for the female matched-control group of rats, survival of all groups of rats and mice was adequate for meaningful statistical analyses of the incidence of tumors. In rats, no tumors occurred at a statistically significant incidence in the treated groups of either sex. In mice, the incidence of hepatocellular carcinoma in low-dose males was significant when compared with that in the pooled controls (controls 5/49, low-dose 19/49, P=0.001). This finding, by itself, is insufficient to establish the carcinogenicity of lindane. The incidence of hepatocellular carcinoma in high-dose male mice (9/46) was not significantly different from that in the matched (2/10) or pooled controls. It is concluded that under the conditions of this bioassay, lindane was not carcinogenic for Osborne-Mendel rats or B6C3F1 mice.