醚菌酯原药对SD大鼠亚慢性经口毒性研究

发布时间：2019-07-18 10:25

【摘要】：目的通过亚慢性经口毒性实验获得醚菌酯原药对SD大鼠的最大无作用剂量(NOAEL),初步确定毒作用靶器官。方法选择无特定病原体级健康成年SD大鼠,随机分为低、中、高剂量组和对照组共4组,每组22只,雌雄各半。3个剂量组大鼠分别用醚菌酯原药水平为690.00、2 750.00、11 000.00 mg/(kg·d)饲料连续喂养90 d,对照组动物给予标准饲料喂养。观察大鼠体质量、尿常规、血常规、血生化和脏器系数改变情况。结果 1雄性高剂量组大鼠在染毒第6、11和12周体质量均低于雄性对照组(P0.05)。24组大鼠尿常规检查结果均正常。3雌性低、中和高剂量组大鼠白细胞(WBC)计数均低于雌性对照组(P0.05),染毒剂量与WBC计数呈剂量-效应关系(Spearmans相关系数为-0.707,P0.01)。与雄性对照组比较,雄性高剂量组大鼠红细胞计数下降(P0.05),平均红细胞血红蛋白浓度升高(P0.05)。4与雄性对照组比较,雄性高剂量组大鼠丙氨酸氨基转移酶活力升高(P0.05),球蛋白水平下降(P0.05)。5雄性高剂量组大鼠肝脏脏器系数高于雄性对照组(P0.05);雌性和雄性的3个剂量组大鼠均出现轻度肝细胞水肿,但与同性别对照组比较差异均无统计学意义(P0.05)。6雌性大鼠NOAEL为小于77.83 mg/(kg·d),雄性大鼠NOAEL为257.68 mg/(kg·d)。结论醚菌酯原药大鼠经口毒性效应主要表现为对血液和肝脏的毒性作用,肝脏可能是其重要的毒性靶器官。
[Abstract]:Objective to obtain the maximum dose of etheria Ether ester on SD rats by subchronic oral toxicity test. (NOAEL), was used to determine the toxic target organs. Methods healthy adult SD rats without specific pathogen grade were randomly divided into 4 groups: low, middle, high dose group and control group, 22 rats in each group, half male and half female. The rats in 3 dose groups were fed with etheria ester diet 690.0, 2.750.0, 11 000.00 mg/ (kg 路d) for 90 days, and the control group was fed with standard diet. The changes of body mass, urine routine, blood biochemistry and organ coefficient were observed. Results 1the body mass of male rats in the high dose group was lower than that in the male control group at the 6th, 11th and 12th week (P 0.05). The results of routine urine examination in 24 groups were normal. 3 the white blood cell (WBC) count in the female low, middle and high dose group was lower than that in the female control group (P 0.05), and there was a dose-effect relationship between the dose and WBC count (Spearmans correlation coefficient was-0.707, P 0.01). Compared with the male control group, the red blood cell count and the average erythrocyte hemoglobin concentration in the male high dose group were lower than those in the male control group (P 0.05). 4 compared with the male control group, the alanine aminotransferase activity and globulin level in the male high dose group were higher than those in the male control group (P 0.05). 5 the liver organ coefficient of the male high dose group was higher than that of the male control group (P 0.05). Mild hepatoedema was found in the three dose groups of female and male, but there was no significant difference compared with the control group (P 0.05). 6 the NOAEL of female rats was less than 77.83 mg/ and that of kg 路d), male rats was 257.68 mg/ (kg 路d). Conclusion the oral toxicity of etheria ester in rats is mainly toxic to blood and liver, and the liver may be an important toxic target organ.
【作者单位】：广东省职业病防治院毒理实验所广东省职业病防治重点实验室;
【基金】：广东省职业病防治重点实验室(2012A061400007)
【分类号】：R114

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