Bioassay of chlorobenzilate for possible carcinogenicity.

Abstract

A bioassay of technical-grade chlorobenzilate for possible carcinogenicity was conducted using Osborne-Mendel rats and B6C3F1 mice. Chlorobenzilate was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Chlorobenzilate was administered for 78 weeks followed by an observation period of 12 or 13 additional weeks in mice and 32 or 33 additional weeks in rats. The time-weighted average dietary concentrations of chlorobenzilate were 2,995 and 1,600 ppm for high and low dose male rats, respectively, and 2,229 and 1,175 ppm for high and low dose female rats. Mice received time-weighted average high and low dietary concentrations of 7,846 and 4,231 ppm, respectively, for males and 5,908 and 3,200 ppm, respectively, for females. Survival in both species was high (over 68 percent of the high dose rats and over 82 percent of the high dose mice survived on test until the end of the study). Dose-related mean body weight depression, observed in both species, indicated that the maximum dose for optimal bioassay sensitivity was used in the high dose groups. An increased incidence of hepatocellular carcinomas was observed in dosed mice, i.e., 4/19 (21 percent) in control males, 32/48 (67 percent) in low dose males, 22/45 (49 percent) in high dose males, 0/20 in control females, 11/49 (22 percent) in low dose females, and 13/50 (26 percent) in high dose females. There was a statistically significant positive association between the administration of chlorobenzilate and the appearance of cortical adenoma of the adrenal gland in low dose male and high dose female rats. Although suggestive, the findings of a low incidence of benign adrenal tumors was not considered sufficient evidence to establish the carcinogenicity of chlorobenzilate for the Osborne-Mendel rat. Under the conditions of this bioassay, orally administered chlorobenzilate was carcinogenic in male and female B6C3F1 mice, causing an increased incidence of hepatocellular carcinomas. The results do not, however, provide sufficient evidence for the carcinogenicity of chlorobenzilate in Osborne-Mendel rats.