Abstract
Four-week repeated-dose toxicity of Kamiguibitang was investigated in rats. Male Sprague-Dawley rats were orally administered with Kamiguibitang at doses of 200, 800, 1,600 or 3,200 mg/kg/day or its vehicle for 28 days. There were no significant differences in the body weight gain between vehicle control and Kamiguibitang-treated groups. Significant changes in daily feed intake and water consumption were not observed throughout the experimental period. There were trends of increase in platelets and white blood cells, in parallel with increases in serum globulin level and spleen weight, suggestive of inflammatory response and/or immune enhancement. Serum parameters of hepatic and renal injuries, such as aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, triglyceride, creatinine, phosphorus, calcium, sodium and potassium, also increased at low doses (200800 mg/kg) of Kamiguibitang, although the levels were suppressed at high doses (1,600-3,200 mg/kg). However, no gross and histopathological lesions were seen at all doses. Based on the results, no observed adverse effect level (NOAEL) of Kamiguibitang was found to be lower than 200 mg/kg, which is comparable with clinical dose (100 mg/kg) in human. In spite of the relatively-low NOAEL, it is suggested that repeated treatment with Kamiguibitang may not exert considerable adverse effects, as inferred from that major hematological and blood biochemical changes were results of pharmacological effectiveness on immunomodulation, and that no histopathological lesions were exerted up to 32 folds of clinical dose (3,200 mg/kg).