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目的研究大鼠灌胃MNT-016重复染毒90 d的毒性反应,为其毒性评价提供参考资料。方法设玉米油为对照溶剂,MNT-016以5、20、80 mg/kg连续90 d灌胃给予SD大鼠,进行临床症状、体质量、血液学、血液生化学及病理组织学等检查;观察动物出现的毒性效应,获得未观察到有害作用剂量(NOAEL);通过基准剂量法求得基准剂量的可信限下限值(BMDL)。结果与溶剂对照组相比,雄性动物AST、TBIL、DBIL、Crea呈剂量依赖性升高,TG、CHOL呈降低趋势;高剂量组雄性动物体质量(解剖前)、心脏、肝脏、胸腺、附睾质量显著降低,脑系数、肺脏系数显著升高;雌性动物体质量(解剖前)及胸腺质量显著降低,肺脏系数显著升高。高剂量组可致肝细胞空泡变性、肾小管嗜碱性病变,中、低剂量组可致肝细胞空泡变性、个别肾小管萎缩,雄性动物病变发生率更高。结论 MNT-016的NOAEL值雄性动物小于5 mg/kg体质量,雌性动物为5 mg/kg体质量。BMDL值雄性动物为2.65 mg/kg,比相应NOAEL更准确;雌性动物为9.04 mg/kg,略大于相应的NOAEL。
Objective To study the toxicity of MNT-016 for 90 days in rats after repeated intragastric administration, and provide references for its toxicity evaluation. Methods Maize oil was used as a control solvent. MNT-016 was given intragastrically to SD rats at 5, 20 and 80 mg / kg for 90 days. The clinical symptoms, body weight, hematology, blood biochemistry and histopathology were examined. The observed toxic effects of the animals were observed for a NOAEL; the lower limit of confidence (BMDL) for the baseline dose was determined by the base-dose method. Results Compared with the solvent control group, the serum levels of AST, TBIL, DBIL and Crea in the male animals increased in a dose-dependent manner and the concentrations of TG and CHOL decreased. The body weight of the male animals (pre-anatomical), heart, liver, thymus and epididymis The quality of the females was significantly lower, the brain coefficient and lung coefficient increased significantly. The body weight (pre-anatomical) and the thymus weight of the females were significantly decreased, while the lung coefficient was significantly increased. High-dose group can cause hepatocyte vacuolar degeneration, basophilic renal tubular lesions, medium and low dose group can cause hepatocyte vacuolar degeneration, individual tubular atrophy, male animal lesions higher incidence. Conclusions NOAEL values for MNT-016 are less than 5 mg / kg for male animals and 5 mg / kg for female animals. The BMDL was 2.65 mg / kg in the male, more accurate than the corresponding NOAEL; the female was 9.04 mg / kg, slightly larger than the corresponding NOAEL.