Bioassay of picloram for possible carcinogenicity.
A bioassay of technical-grade picloram for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered picloram in the diet at one of the following doses for 80 weeks. Time-weighted average doses for the rats were 7,437 or 14,875 ppm; those for the mice were 2,531 or 5,062 ppm. The rats were then observed for 33 weeks, the mice for 10 weeks. Matched controls consisted of groups of 10 untreated rats or 10 untreated mice of each sex; pooled controls, used for statistical evaluation, consisted of the matched control groups combined with 33 untreated male and 30 untreated female rats or mice from similar bioassays of three other test chemicals. All surviving rats were killed at 113 weeks; all surviving mice were killed at 90 weeks. Survival was adequate for meaningful statistical analyses of the incidences of tumors in rats and mice of both sexes. Mean body weights of the high-dose rats were lower than those of matched controls during the first part of the study; however, beginning at approximately 80 weeks, mean weights of controls were lower than those of treated animals. Body weights of the mice were unaffected by the picloram. In rats, a relatively high incidence of follicular hyperplasia, C-cell hyperplasia, and C-cell adenoma of the thyroid occurred in both sexes. However, the statistical tests for adenoma did not show sufficient evidence for association of the tumor with picloram administration. An increased incidence of hepatic neoplastic nodules was observed in treated male and female rats as compared with untreated animals. This lesion is considered to be a benign tumor. In male rats the lesion appeared only in three animals of the low-dose treatment group and was not significant when compared with the controls; however, the test for positive dose-related trend in females was significant (pooled controls 0/39, low-dose 5/50, high-dose 7/49, P=0.016) and the incidence in the high-dose group was significant (P=0.014) when compared with that in the pooled-control group. There was also one hepatocellular carcinoma in a low-dose male rat and one in a high-dose female rat. In both males and females, there was a possibly treatment-related lesion of the liver diagnosed as foci of cellular alteration. The incidences of this latter lesion were, female rats: matched controls 1/10, low-dose 8/50, high-dose 18/49; male rats: matched controls 0/10, low-dose 12/49, high-dose 5/49. Thus, there is evidence that picloram affected the livers of rats of both sexes, but more particularly those of the females. No tumors were found in male or female mice or male rats at incidences that could be significantly associated with treatment, and it is concluded that picloram was not carcinogenic for B6C3F1 mice or male Osborne-Mendel rats. In female rats, however, the incidence of neoplastic nodules of the liver, benign tumors, was associated with treatment with picloram. It is concluded that under the conditions of the bioassay, the findings are suggestive of the ability of the compound to induce benign tumors in the livers of female Osborne-Mendel rats.