Bioassay of Phenformin for Possible Carcinogenicity (CASRN 114-86-3)*
Chemical Formula: C10H15N5 · HCl
Phenformin is a synthetic oral hypoglycemic agent used to control maturity-onset diabetes. Pharmacologically, phenformin acts to enhance anaerobic glycolysis, decrease gluconeogenesis, and inhibit intestinal absorption of glucose. This compound was selected for carcinogenicity testing since, in the treatment of diabetes, it is administered chronically.
A bioassay of the carcinogenicity of phenformin hydrochloride was conducted using Fischer 344 rats and B6C3F1 mice. The compound was administered in the diet for 78 weeks to groups of 35 animals of each species and sex, using concentrations of 15,000 and 30,000 ppm for rats and concentrations of 1,200 and 2,500 ppm for mice. Treatment was followed by a period of observation of 26 weeks. Control groups consisted of 15 untreated animals of each species and sex.
Average weights attained by treated groups of rats and mice were consistently lower than those of control groups in all tests except that for male rats, in which case the weights shown by treated and control animals were indistinguishable. Survival was apparently unaffected in both species bytreatment with phenformin, but was poor in mice due to intercurrent disease.
Tumors appearing in treated rats and mice were similar in type and number to those in controls, and no pathologic or statistical evidence of induction of tumors in these species by phenformin was found.
Synonym: 1-phenethylbiguanide hydrochloride
*The technical report states that Phenformin Hydrochloride (CASRN 834-28-6) was the actual chemical tested rather than Phenformin in its pure form; therefore, the CASRN for Phenformin Hydrochloride is used to track this study in the NTP CHEMTRACK database.
Report Date: January 1977