P27: Thirteen-week repeated dose toxicity and genetic toxicity studies of processed genkwa flos extract

Genkwa flos has been used for the treatment of edema in the face or body, ascites, retention of fluids in the chest, sudden cough, scabs, white ringworm and stubborn ringworm. Crude Genkwa flos should not be taken unless the toxicity is removed. To remove the toxicity of crude Genkwa flos, some processing method should be applied. However, potential toxicity of the processed Genkwa flos extract (PGFE) was not yet determined. Therefore, we performed 13-week repeated dose toxicity and genetic toxicity studies to evaluate the no-observed-adverse-effect-level (NOAEL) and genotoxicity of PGFE. Based on 14-day dose-range-finding study, groups of 60 male and 60 female F344 rats were treated orally at different dosages (0, 25, 74, 222, 667, and 2000 mg/kg B.W.) of PGFE for 13 weeks. No PGFE-related effect were observed in various parameters included mortality; clinical signs; body weight changes; food and water consumption; hematology and serum biochemistry; male and female reproductive tissue evaluations; gross and histopathological findings. However, male and female liver weights were significantly increased at dose 667 and 2000 mg/kg. Therefore, NOAEL of PGFE might be thought under 667 mg/kg in male and female F344 rats. In reverse mutation assay, TA98, TA102 and TA1537 were 2-fold increased at 5000μg/plate without metabolic activation. TA1537 were significantly increased up to 5000μg/plate dose dependently. These results suggest that PGFE might have reverse mutagenicity under the condition of this study. In chromosome aberration test, there was no significant increase in the number of structural or numeric aberrant metaphases at any dose with or without metabolic activation. A micronucleus test of PGFE was performed using ICR mice. Frequency of MNPCEs and ratio PCE were not increased at any doses.