A 13-week repeated oral dose toxicity evaluation and a 4-week recovery evaluation of rosemary concentrate containing 50% ursolic acid in male and female rats

Abstract

This study was performed to evaluate the safety of rosemary concentrate containing 50% ursolic acid (RCUA50), the ethanolic extract of rosemary. RCUA50 was administered orally for 13 weeks at 1000, 2000, and 4000 mg/kg/day, and then the rats were maintained for 4 weeks without RCUA50 administration for recovery evaluation. We observed clinical signs, body weights, food consumption, functional observations, ophthalmological examination, urinalysis, estrus cycle, hematology, clinical chemistry, sperm analysis, organ weights, gross examination, and histopathological examinations. During the dosing and recovery period, there were no test substance-related deaths, clinical signs, changes in body weights, and food consumption in all treated groups. In the main group, there were no test substance-related effects in functional observations and ophthalmological examination. In the main and recovery groups, there were no test substance-related effects in hematology, clinical chemistry, sperm analysis, organ weights, necropsy and histopathological examination. In conclusion, the repeated oral administration of RCUA50 for 13 weeks resulted in no test substance-related adverse effect at all dose levels. Therefore, the NOAEL was considered to be greater than 4000 mg/kg/day in both sexes under the conditions of this study.