title: Bioassay of clonitralid for possible carcinogenicity.
abstract: A bioassay for possible carcinogenicity of clonitralid was conducted using Osborne-Mendel rats and B6C3F1 mice. Clonitralid was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The time-weighted average high and low dietary concentrations of clonitralid were, respectively, 28,433 and 14,216 ppm for rats and 549 and 274 ppm for mice. After a 78-week period of compound administration, there was an additional observation period of 32 to 33 weeks for rats and 13 to 14 weeks for mice. Adequate numbers of male rats, female rats, and female mice survived long enough to be at risk from late-developing tumors. Because of inadequate survival among male mice, however, results obtained from observation of the male mouse groups cannot be considered conclusive. The incidences of mammary adenocarcinomas in treated female rats were not significantly higher than the incidences observed in control female rats. However, the incidences of this lesion in dosed female rats were greater than or equal to 22 percent, while the highest incidence observed in 15 control groups at this laboratory was only 10 percent with a mean incidence of 2.6 percent. The occurrence in high dose female rats (2/45) of carcinomas in the glandular portion of the stomach with metastases to other sites was not statistically significant. This incidence, however, is much greater than the historical control incidence and suggests an association between administration of clonitralid and the development of these tumors. No statistically significant increased tumor incidences were observed among male rats or mice of either sex dosed with clonitralid. Under the conditions of this bioassay, there was no convincing evidence that clonitralid was carcinogenic to Osborne-Mendel rats or to female B6C3F1 mice. Poor survival of male mice did not permit an evaluation of carcinogenicity in these animals.