Toxicology and carcinogenesis studies of isophorone in F344 rats and B6C3F1 mice.

Toxicology and carcinogenesis studies of isophorone were conducted by administering 0, 250, or 500 mg/kg body weight per day by gavage in corn oil to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days/week, for 103 weeks. Dosed male rats developed proliferative lesions of the kidney including hyperplasia, adenoma, and adenocarcinoma of the renal tubule, and epithelial hyperplasia of the renal pelvis. Non-proliferative kidney lesions observed in dosed male rats included mineralization, and a more severe nephropathy in low dose animals than in controls or high dose animals. Carcinomas of the preputial gland occurred in high dose male rats. No isophorone-related lesions were observed in female rats. In male mice, isophorone exposure may have been associated with an increase in hepatocellular neoplasms and mesenchymal neoplasms of the integumentum in high dose animals, and with a marginally increased incidence of lymphoma in low dose male mice. In mice, no non-neoplastic lesions in males or females, or neoplastic lesions in females were considered associated with isophorone administration.