Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 4 No. 2 March 17, 2017 p.45-56
Original Article
Oral acute and chronic toxicity studies of β, β-dimethylacrylalkannin in mice and rats
  • Hong-Tao Jin (New Drug Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, China / Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., China / jinhongtao@imm.ac.cn)
  • Jin-Feng Wei (New Drug Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, China / Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., China / weijinfeng@imm.ac.cn)
Piao-Piao Zhang 1) , Xiao-Dan Yan 1) , Xiao-Yu Fan 1) , Ya-Hao Ling 1) , Chao Li 2) , Lin Lin 1) , Dan Qin 1) , Tian-Tian Liu 1) , Ye Li 1) , Hui Li 1) , Qianqian Zhang 1) , Wen-Bo Mu 2) , Ai-Ping Wang 1) 2) , Hong-Tao Jin 1) 2) , Jin-Feng Wei 1) 2)
1) New Drug Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, China , 2) Beijing Union-Genius Pharmaceutical Technology Development Co., Ltd., China
Keywords: Lithospermum erythrorhizon, β, β-dimethylacrylalkannin, Acute toxicity, Chronic toxicity, Pigmentation
Abstracts

β, β-dimethylacrylalkannin is a major active chemical component extracted from Lithospermum erythrorhizon, a traditional Chinese medicine that exhibits strong antimicrobial, anti-cancer and anti-inflammatory activities. However, its potential toxicity has not been rigorously studied. To confirm its safety, the oral toxicity of β, β-dimethylacrylalkannin was evaluated in vivo. An acute oral toxicity study in mice demonstrated that β, β-dimethylacrylalkannin was practically nontoxic based on its high median lethal dose (LD50 > 10 g/kg). No deaths or abnormal responses were observed in the acute toxicity test using Wistar rats, suggesting that the maximum tolerated dose of β, β-dimethylacrylalkannin was greater than 10 g/kg. Chronic toxicity studies also revealed an absence of mortality and clinical symptoms, and no treatment-related adverse effects were detected by hematology, blood biochemistry and urinalysis examinations in all rats treated with 10-160 mg/kg/day β, β-dimethylacrylalkannin during a 6-month period. Increases in the relative organ weight of the lungs of females and the liver of males were observed at 160 mg/kg. Histopathological analyses revealed brown pigmentation in renal tubular epithelial cells at the middle and high doses (40-160 mg/kg/day). The no-observed-adverse-effect level (NOAEL) of β, β-dimethylacrylalkannin is 10 mg/kg/day. These results suggest that β, β-dimethylacrylalkannin is potentially safe for further development as a therapeutic agent in humans.