Abstract for TR-50

Bioassay of Acetohexamide for Possible Carcinogenicity

CASRN: 968-81-0
Chemical Formula: C15H20N2O4S
Molecular Weight: 324.399
Synonyms/Common Names: 1-[(p-acetylphenyl)-sulfonyl]-3-cyclohexylurea
Report Date: 1978

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Acetohexamide is an oral hypoglycemic agent of the arylsulfonyl-urea group with a potency between that of tolbutamide and chlorpropamide.

A bioassay of acetohexamide for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice.

Groups of 35 rats of each sex were administered acetohexamide in the diet at one of two doses, either 10,000 or 20,000 ppm, for 103 weeks and then observed for 2 to 4 additional weeks. Matched controls consisted of 15 untreated rats of each sex. All surviving rats were killed at 105 to 107 weeks.

Groups of 35 mice of each sex were administered acetohexamide at one of two doses for 103 weeks and then observed for 4 or 5 additional weeks. Time-weighted average doses were 6,359 or 12,718 ppm. Matched controls consisted of 15 untreated mice of each sex. All surviving mice were killed at 107 or 108 weeks.

Mean body weights of the dosed rats and mice of both sexes were lower than those of the corresponding matched controls throughout the study, and the depressions in weight were dose related. Except for the female mice, sufficient numbers of animals survived long enough to be at risk for development of late-appearing tumors.

In the rats, the only tumor occurring with greater incidence in dosed than in matched-control animals was leukemia (males: matched controls 0/15, low-dose 10/35, high-dose 4/35; females: matched controls 0/14, low-dose 7/35, high-dose 4/34). Only the incidence in the low-dose males was statistically significant (P=0.018). All of these animals had undifferentiated (mononuclear cell) leukemia, which commonly occurs spontaneously in Fischer 344 rats, except for two with lymphocytic leukemia. The incidence of combined leukemia and lymphoma in historical-control male rats at this laboratory in the bioassay program to date is 24/235 (10.2%), which is higher than that in the matched controls. Thus, the incidence in the low-dose males cannot be clearly associated with administration of the test chemical.

In the mice, the only neoplasms that occurred at a higher incidence in dosed groups than in matched controls were lymphomas in the males, but the incidences were not statistically significant (matched controls 1/15, low-dose 9/35, high-dose 3/34). These types of lesions are found commonly in untreated B6C3F1 mice. The incidence of lymphomas in the historical-control male mice is 28/536 (5.2%).

It is concluded that under the conditions of this bioassay, acetohexamide was not carcinogenic for either Fischer 344 rats or B6C3F1 mice.