Toxicology and carcinogenesis studies of ginseng (CAS No. 50647-08-0) in F344/N rats and B6C3F1 mice (gavage studies).

Unlabelled: CHEMICAL AND PHYSICAL PROPERTIES: Ginseng is a perennial aromatic herb widely used in herbal remedies, dietary supplements, cosmetics, and as a food additive. Ginseng was nominated for study by the National Cancer Institute based on significant human exposure through the uses described above and the lack of information on its toxicity. Male and female F344/N rats and B6C3F1 mice were administered extracts of ginseng root by gavage for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were administered ginseng in 0.5% aqueous methylcellulose by gavage at doses of 0, 125, 250, 500, 1,000, or 2,000 mg/kg, 5 days per week for 16 days. All rats survived to the end of the study. Mean body weight gain of 2,000 mg/kg males was significantly greater than that of the vehicle controls. There were no chemical-related gross or microscopic findings attributed to the administration of ginseng. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were administered ginseng in 0.5% aqueous methylcellulose by gavage at doses of 0, 125, 250, 500, 1,000, or 2,000 mg/kg, 5 days per week for 17 days. All mice survived to the end of the study. The final mean body weight of 1,000 mg/kg males was significantly less than that of the vehicle controls. There were no significant chemical-related gross or histopathologic changes in dosed mice. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered ginseng in sterile water by gavage at doses of 0, 1,000, 2,000, 3,000, 4,000, or 5,000 mg/kg, 5 days per week for 14 weeks. All rats survived to the end of the study. Mean body weights of all dosed groups were similar to those of the vehicle control groups. No lesions that were observed by gross or histopathologic examination were attributed to the administration of ginseng. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered ginseng in sterile water by gavage at doses of 0, 1,000, 2,000, 3,000, 4,000, or 5,000 mg/kg, 5 days per week for 14 weeks. All mice survived to the end of the study. Mean body weights of all dosed groups were similar to those of the vehicle control groups. Although sporadic incidences of lesions were observed in the vehicle control and 5,000 mg/kg groups, there were no chemical-related gross or microscopic findings in dosed mice. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered ginseng in sterile water by gavage at doses of 0, 1,250, 2,500, or 5,000 mg/kg, 5 days per week for 104 to 105 weeks. Survival of 5,000 mg/kg females was significantly less than that of the vehicle controls; however, the deaths were not attributed to the administration of ginseng because no histopathologic findings attributable to ginseng were found. Mean body weights of 5,000 mg/kg females were less than those of the vehicle controls after week 61 of the study, and mean body weights of other dosed groups of rats were similar to those of the vehicle controls throughout the study. No increases in the incidences of neoplasms or nonneoplastic lesions were attributed to the administration of ginseng. The incidence of mammary gland fibroadenoma was significantly decreased in 5,000 mg/kg females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered ginseng in sterile water by gavage at doses of 0, 1,250, 2,500, or 5,000 mg/kg, 5 days per week for 105 weeks. Survival of dosed groups was similar to that of the vehicle control groups. Mean body weights of dosed mice were similar to those of the vehicle controls. No neoplasms or nonneoplastic lesions were attributed to the administration of ginseng.

Genetic toxicology: Ginseng was not mutagenic in either of two independent bacterial mutagenicity assays, each conducted with or without exogenous metabolic activation enzymes. Bacterial strains tested included S. typhimurium strains TA97, TA98, TA100, TA102, TA104, and TA1535, as well as E. coli strain WP2 uvrA/pKM101. No significant increases were seen in the frequencies of micronucleated erythrocytes in the peripheral blood of male or female B6C3F1 mice exposed for 3 months to 1,000 to 5,000 mg/kg ginseng via gavage.

Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of ginseng in male or female F344/N rats or B6C3F1 mice administered 1,250, 2,500, or 5,000 mg/kg. The incidence of mammary gland fibroadenoma was significantly decreased in 5,000 mg/kg female rats.