Ninety-day repeated oral toxicity and genetic toxicity studies of powderized Aurantii Fructus Immaturus

Aurantii Fructus Immaturus (AFI) has been widely used as an herbal medicine for health promotion and the treatment of various diseases but there is little information on its toxicity. Herein, we performed general and genetic toxicity studies on the powdered form of AFI. The lethal dose 50 % (LD₅₀) of AFI powder in Sprague-Dawley (SD) rats was >4000 mg/kg for both sexes. The 28-day repeated oral toxicity study of AFI powders at 0, 125, 250, 500, 1000, and 2000 mg/kg/day showed some occasional changes including soiled perineal region, loss of fur, and weight loss. However, these changes were not considered treatment-related because the values were within the control range and responses were not dose-dependent. The 90-day repeated oral toxicity study with a 4-week recovery period of AFI powders in rats at 0, 125, 250, 500, 1000, and 2000 mg/kg/day also showed no treatment-related toxicity outcomes, although some endpoints showed significant changes such as loss of fur, increased MCH and MCV levels, and increased liver weight. Therefore, the no-observed-adverse-effect level (NOAEL) of AFI powders in rats was 2000 mg/kg/day. Finally, a battery of three genotoxicity tests showed that the AFI powder was not a genotoxic material.