Single and 90-day repeated oral dose toxicity studies of fermented Rhus verniciflua stem bark extract in Sprague–Dawley rats

Fermented Rhus verniciflua stem bark (FRVSB) extract, an urushiol-free extract of Rhus verniciflua Stokes (RVS) fermented with Fomitella fraxinea, has various biological activities. The present study was carried out to investigate the potential toxicity of the FRVSB extract following single and repeated oral administration to Sprague–Dawley rats. In the single dose toxicity study, the FRVSB extract was administered orally to male and female rats at single doses of 0, 2500, 5000, and 10,000 mg/kg. No animals died and no toxic changes were observed in clinical signs, body weight, and necropsy findings during the 15-day period following administration. In the repeated dose toxicity study, the FRVSB extract was administered orally to male and female rats for 90 days at doses of 0, 556, 1667, and 5000 mg/kg/day. There were no treatment-related adverse effects in clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at any dose tested. The approximate lethal dose of the FRVSB extract was >10,000 mg/kg in both genders, the oral no-observed-adverse-effect level of the FRVSB extract was >5000 mg/kg/day in both genders, and no target organs were identified.