Toxicity of a novel anti-tumor agent 20(S)-ginsenoside Rg3: a 26-week intramuscular repeated administration study in Beagle dogs.

The potential subchronic toxicity of a dammarane-type triterpenoid saponin with antitumor effect, 20(S)-Ginsenoside Rg3, was studied repeated intramuscular administration in Beagle dogs over a 26-week period. 20(S)-Ginsenoside Rg3 was administrated intramuscularly at 0, 0.70, 2.86 or 7.20 mg/kg/day doses for 26 weeks in both male and female dogs (n = 4 for male and female dogs for each dose). During the test period as well as during the 8-week recovery period, clinical signs, mortality, body weights, food consumption, respiratory frequency, electrocardiogram, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. In dogs treated with doses of 2.86 or 7.20 mg/kg, hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) count and in the percentage of neutrophils, but a decrease in the percentage of lymphocytes. These effects were completely reversed during the recovery period, and no other adverse effects were observed. The no-observed-adverse-effect levels for both male and female dogs were considered to be 7.20 mg/kg/day.