应用基准剂量法评估MNT-016的亚慢性毒性

发布时间：2018-05-05 23:43

本文选题：MNT- + Sprague-Dawley大鼠　；参考：《军事医学》2017年06期

【摘要】：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。
[Abstract]:Objective to study the toxicity of MNT-016 repeated exposure to 90 d in rats, and to provide reference materials for its toxicity evaluation. Methods corn oil was used as a control solvent and MNT-016 was given to SD rats with 5,20,80 mg/kg for 90 d, and the clinical symptoms, body mass, hematology, hematology and histopathology were examined, and the toxicity of the animals was observed. Effect, obtain unobserved dose of harmful dose (NOAEL); obtain the confidence limit value (BMDL) of baseline dose by reference dose. Results compared with the solvent control group, male animals AST, TBIL, DBIL, Crea were dose-dependent, TG, CHOL showed a decreasing trend; high dose group male body mass (before dissection), heart, liver, thymus, epididymis The mass of the body mass (before dissection) and the mass of the thymus significantly decreased and the lung coefficient increased significantly. The high dose group could cause the vacuolation of the hepatocyte and the basophilic tubule of the renal tubules, and the low dose group could cause the vacuolation of the hepatocytes, some renal tubules atrophy and the incidence of the male animal disease. Conclusion the NOAEL value of MNT-016 is less than 5 mg/kg body mass, and the female animal is 2.65 mg/kg with 5 mg/kg body mass.BMDL, and the female animal is more accurate than the corresponding NOAEL; the female animal is 9.04 mg/kg, slightly larger than the corresponding NOAEL..

【作者单位】：沈阳药科大学生命科学与生物制药学院;解放军疾病预防控制所毒理学评价研究中心;北京卫生职业学院;
【基金】：国家自然科学基金重点资助项目(81430090)
【分类号】：R99

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