National Toxicology Program

TR-31
Bioassay of Tolbutamide for Possible Carcinogenicity
(CAS No. 64-77-7)

Tolbutamide was the first oral hypoglycemic agent used in the management of diabetes. It is one of the arylsulfonylurea hypoglycemics, a group which included tolazamide, chlorpropamide, and acetohexamide. All of these compounds function by stimulating the secretion of insulin by the pancreas and, therefore, are used only in patients with at least minimal pancreatic function, as in maturity-onset diabetics.

A bioassay of tolbutamide for possible carcinogenicity was conducted by administering the test material in the diet to Fischer 344 rats and B6C3F₁ mice.

Groups of 35 rats of each sex were administered tolbutamide at one of two doses, either 12,000 or 24,000 ppm, 5 days a week for 78 weeks, then observed for an additional 28 weeks. Matched-control groups consisted of 15 untreated rats of each sex. All surviving rats were killed at 106 or 107 weeks.

Groups of 35 mice of each sex were administered tolbutamide at one of two doses, either 25,000 or 50,000 ppm, 5 days a week for 78 weeks, then observed for an additional 24-26 weeks. Matched-control groups consisted of 15 untreated mice of each sex. All surviving mice were killed at 102-104 weeks.

Mean body weights of the treated rats and mice were lower than those of the corresponding matched controls during the entire study; however, survival was not significantly affected by treatment in either species. In both sexes of both species, survival was considered to be adequate for meaningful statistical analyses of the incidence of tumors.

In both the rats and the mice, a variety of neoplasms were found in both tolbutamide-treated and control groups. None of the neoplasms were present at a statistically significant increased incidence in treated groups of either species as compared with control groups and were not considered to be compound related.

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

Synonym: 1-butyl-3-(p-methylbezenesulfonyl)urea

Levels of Evidence of Carcinogenicity:
Male Rats: Negative
Female Rats: Negative
Male Mice: Negative
Female Mice: Negative

Report Date: 1977

Target Organs from 2-year Studies

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