Chlorpropamide is an oral hypoglycemic agent of the arylsulfonylurea type. Chlorpropamide was selected for testing in the carcinogenesis program because it is used extensively and for prolonged periods in humans.
A bioassay of chlorpropamide for possible carcinogenicity was conducted by administering the test material in feed to Fischer 344 rats and B6C3F1 mice.
Groups of 35 rats and 35 mice of each sex were administered chlorpropamide as follows: rats 5 days per week for 103 to 105 weeks at 3,000 or 6,000 ppm, and mice 5 days per week for 34 weeks at 5,000 or 10,000 ppm, followed by 70 weeks at 2,500 or 5,000 ppm. The time-weighted average doses for mice were 3,317 ppm for low-dose males and females, and 6,635 ppm for high-dose males and females. Matched controls consisted of groups of 15 untreated rats and 15 untreated mice of each sex. All surviving rats and mice were killed at 103 to 105 weeks.
Mean body weights of both low- and high-dose rats were lower than those of the matched controls throughout the study. In mice, doses were reduced at week 34, due to early deaths in the high-dose groups; following this adjustment the treated mice gained weight, but the weights never reached those of the controls. Survival of the treated rats and the low-dose mice was adequate for meaningful statistical analyses of the incidences of tumors.
In both rats and mice, the incidences of tumors among the treated groups were not significantly increased in comparison with matched controls.
It is concluded that under the conditions of this bioassay, chlorpropamide was not carcinogenic for Fischer 344 rats or B6C3F1 mice.