title: NTP Toxicology and Carcinogenesis Studies of d-Carvone (CAS No. 2244-16-8) in B6C3F1 Mice (Gavage Studies).
abstract: d-Carvone occurs naturally in caraway and dill seeds and in many essential oils; it has been used as a carminative and in perfumes and soaps. Toxicity and carcinogenesis studies were conducted by administering d-carvone (approximately 96% pure) in corn oil by gavage to groups of male and female B6C3F1 mice for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Sixteen-Day Studies: All mice that received 1,600 or 3,500 mg/kg died within 7 days. Relative liver weights were increased for dosed male mice, and relative thymus weights were decreased for dosed female mice. No compound-related lesions were observed. Thirteen-Week Studies: All male mice and 9/10 female mice that received the top dose of 1,500 mg/kg died before the end of the studies. No compound-related histopathologic changes were observed. Based on survival at the high doses in the 13-week studies, 2-year NTP Toxicology and Carcinogenesis studies were conducted by administering d-carvone in corn oil by gavage to groups of 50 male and 50 female mice at doses of 375 or 750 mg/kg, 5 days per week for 103 weeks. Two-Year Studies: Mean body weights of dosed and vehicle control mice were similar throughout the studies. Survival of dosed male mice was similar to that of vehicle controls (vehicle control, 37/50; low dose, 42/50; high dose, 36/50); survival of dosed female mice was greater than that of vehicle control female mice (14/50; 29/50; 38/50). Apparently, abscesses in the urogenital system caused the early deaths of many vehicle control female mice. No neoplastic lesions attributed to d-carvone dosing were observed in mice. Genetic Toxicology: d-Carvone was not mutagenic in S. typhimurium but induced sister chromatid exchanges and chromosomal aberrations in CHO cells. Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of d-carvone for male or female B6C3F1 mice administered 375 or 750 mg/kg, 5 days per week for 2 years. Synonyms for d-carvone: (+)-carvone; d(+)-carvone; (S)-carvone; (S)-(+)carvone; (S)-2-methyl-5-(1-methylethenyl)-2-cyclohexen-1-one; (S)-d-p-mentha-6-8,(9)-dien-2-one; (S)-(+)-p-mentha-6,8-dien-2-one; d-1-methyl-4-isopropenyl-6-cyclohexen-2-one. Carvol is a synonym for carvone (d, l not specified)