军事医学2017，Vol.41Issue(6)：502-505,519,5.DOI:10.7644/j.issn.1674-9960.2017.06.021
应用基准剂量法评估MNT-016的亚慢性毒性
Sub-chronic toxicity of MNT-016 by benchmark dose method in Sprague-Dawley rats
摘要
Abstract
Objective To evaluate the repeated dose toxicity of MNT-016 in SD rats and to provide reference for toxicity evaluation.Methods MNT-016 was administered to rats at 5, 20 and 80 mg/kg for 90 days.The toxic effects on the animals were evaluated by observing the clinical signs and measuring the body weight, hematology and blood biochemistry as well as histopathological examination.NOAEL and benchmark dose lower confidence limit(BMDL) were observed by the end point of toxicity.Results Compared with the control group, the AST, TBIL, DBIL and Crea of male rats were increased in a dose-dependent manner, while TG and CHOL decreased.The body mass(before anatomy), heart, liver, thymus, epididymis of male rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of the heart and lung was increased.The body mass (before anatomy) and thymus of female rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of lungs was increased.Vacuolation of hepatocytes was observed in groups each dose, tubule atrophy was found in the kidneys of 20 and 5 mg/kg groups, and tubule basophilia was observed in 80 mg/kg group.The incidence of the above lesions was higher in male animals than in female ones.Conclusion The NOAEL of MNT-016 is lower than 5 mg/kg in male rats and 5 mg/kg in female rats.BMDL value is 2.65 mg/kg in male animals and more accurate than NOAEL, and is 9.04 mg/kg in female animals,which is slightly larger than the corresponding NOAEL.关键词
MNT-016/Sprague-Dawley大鼠/亚慢性毒性/基准剂量/NOAELKey words
MNT-016/Sprague-Dawley rats/sub-chronic toxicity/benchmark dose/no observed adverse effect level分类
医药卫生引用本文复制引用
李巧芳,彭辉,何秀姝,赵君,彭双清,吴英良..应用基准剂量法评估MNT-016的亚慢性毒性[J].军事医学,2017,41(6):502-505,519,5.基金项目
国家自然科学基金重点资助项目(81430090) （81430090）
