Acute and subchronic oral toxicity assessment of the herbal formula Kai-Xin-San.

Ethnopharmacological Relevance: Kai-Xin-San (KXS) is a famous traditional Chinese medicine (TCM) formula. It has been used in the treatment of diseases including neurasthenia, Alzheimer's disease and neurosis.

Aim Of The Study: To provide information on the potential toxicity of KXS, we evaluated the acute and subchronic toxicity in rodents.

Materials And Methods: In acute study, a single administration of KXS was given orally to mice at doses ranging from 19.67 to 60.04 g/kg. In the sub-chronic oral toxicity study, KXS was administered to rats at 0, 1, 3 and 9 g/kg for 13 weeks. Moreover, 30 days of post treatment (withdrawal study) was conducted. Mortalities, clinical signs, body weight changes, food and water consumption, haematological and biochemical parameters, gross findings and organ weights were monitored during the study period.

Results: In the sub-chronic study in rats, daily oral administration of KXS at the dose of 9 g/kg/day result in significant increase in WBC, lymphocyte, alkaline phosphatase, blood sugar and significant decrease in bodyweight, serum Cre, CK and CHO at the last week of treatment. Recovery except for the body weight was observed after 30 days of post treatment.

Conclusions: KXS is relatively safe for oral medication. The LD(50) of KXS was over 32.59 g/kg for mice. The no-observed-adverse-effect-level (NOAEL) was considered to be 19.67 g/kg/day for rats.