Toxicology and Carcinogenesis Studies of d-Carvone (CAS No. 2244-16-8) in B6C3F1 Mice (Gavage Studies)
Chemical Formula: C10H14O
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.
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.
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 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.
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.
d-Carvone was not mutagenic in S. typhimurium but induced sister chromatid exchanges and chromosomal aberrations in CHO cells.
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)
Report Date: February 1990