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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(P<0.05)。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(P<0.05),染毒剂量与WBC计数呈剂量-效应关系(Spearmans相关系数为-0.707,P<0.01)。与雄性对照组比较,雄性高剂量组大鼠红细胞计数下降(P<0.05),平均红细胞血红蛋白浓度升高(P<0.05)。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(P<0.05),球蛋白水平下降(P<0.05)。5雄性高剂量组大鼠肝脏脏器系数高于雄性对照组(P<0.05);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(P>0.05)。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。
OBJECTIVE: To determine the maximum effective dose (NOAEL) of kresoxim-methyl in SD rats by sub-chronic oral toxicity test and to determine the target organ of toxicity. Methods Healthy adult SD rats without specific pathogen were randomly divided into 4 groups (low, middle and high dose group) and control group (22 rats in each group). The rats in the three dosage groups were fed with the diets containing 690.00, 2 750.00 and 1 000.00 mg / (kg · d) respectively for 90 days. The control animals were fed with the standard diet. Observe the rat body weight, urine, blood, blood biochemistry and organ coefficient changes. Results The body weight of rats in high-dose and high-dose groups of 1, 6, 11 and 12 weeks after exposure was lower than that of the male control group (P <0.05). Urine routine examination results of 24 rats were normal. The WBC count of female low, medium and high dose groups were lower than that of female control group (P <0.05). The dose-effect relationship of WBC count with dose-effect relationship (Spearmans correlation coefficient -0.707, P <0.01 ). Compared with the male control group, the red blood cell count of male high-dose group decreased (P <0.05) and the average hemoglobin concentration of erythrocyte increased (P <0.05). Compared with the male control group, the alanine aminotransferase activity of the male high dose group increased (P <0.05) and the globulin level decreased (P <0.05). The liver organ coefficient of 5 male high-dose group was higher than that of male control group (P <0.05); mild and severe hepatocyte edema appeared in 3 dose groups of female and male, but no significant difference compared with the same sex control group Statistical significance (P> 0.05). NOAEL in female rats was less than 77.83 mg / (kg · d) and NOAEL in male rats was 257.68 mg / (kg · d). Conclusions The oral toxicity effect of kresoxim-methyl in rats is mainly manifested as toxicity to blood and liver, and the liver may be an important toxic target organ.