Sub-chronic oral toxicity of the aqueous extract of lithospermi radix in Fischer 344 rats

Ethnopharmacological relevance: Lithospermi radix has been prescribed in traditional folk medicine to treat diverse diseases like cancer. Aim of the study: The present study assessed the sub-chronic oral toxicity of an aqueous extract of lithospermi radix (WLR) in Fischer 344 rats over a period of 13 weeks. Materials and methods: The chemical compositions of WLR were analyzed using ultra-high performance liquid chromatography (UHPLC). WLR was daily administered to Fischer 344 rats at 0, 500, 1000, and 2000 mg/kg body weights (bw) for 13 weeks via oral gavage. Changes in mortalities, body weights, and intakes of food and water were monitored during the WLR treatment period. Urine was collected and analyzed 12 h before necropsy. Organ weights, hematological parameters, and plasma biochemical parameters were determined along with histopathological examination. Results: When compared with the normal control group, no remarkable toxic signs or parameter variations related with WLR treatment were observed in mortality, body weights, organ weights, food and water consumptions, urinalysis, hematological and plasma biochemical analyses, and histopathological examination. Mortalities observed in one male at 2000 mg/kg bw and three females at 1000 mg/kg bw were not related with WLR treatment because no gross findings of toxicity were observed in both morphological and histological examination. Some significant changes in clinical parameters or histological lesions observed in WLR-treated animals were not related with WLR treatment because the differences were marginal and did not show dosedependent or directional changes. Conclusions: Based on these findings, the calculated no-observed-adverse-effect-level (NOAEL) in rats was higher than 2000 mg/kg bw.