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(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 evaluate the sub-chronic oral toxicity of kresoxim-methyl in SD rats,and to obtain the no observed adverse effect level( NOAEL) and targeted organs. Methods Specific pathogen free healthy SD rats were randomly divided into low-,middle- and high-dose groups and the control group,22 in each group,half male and half female. Diet with kresoxim-methyl was administrated to the three dose groups rats at the dosages of 690. 00,2 750. 00,and11 000. 00 mg /( kg·d) for 90 days,respectively. The standard diet was fed to the control group. The body weight,urine routine,routine blood,blood biochemistry indexes,organ coefficients,and histopathology examination of the rats were tested or observed. Results a) the body weights in male high-dose group in the 6th,11 th and 12 th week after exposure were significantly lower than those in the male control group( P〈0. 05). b) Routine urine test results were normal in the4 groups. c) The counts of white blood cell( WBC) in female low-,middle- and high-dose groups were significantly lower than that in the female control group respectively( P〈0. 05),and there was a dose-effect relationship between the dosages exposed and WBC counts in female( Spearman coefficient was- 0. 707,P〈0. 01). Compare with the male control group,the count of red blood cell in male high-dose group was significantly lower( P〈0. 05),and the level of mean corpuscular haemoglobin concentration was significantly higherer( P〈0. 05). d) Compare with the male control group,the level of alanine aminotransferase in male high-dose group was significantly higher( P〈0. 05),while the globulin level were significantly lower( P〈0. 05). e) The liver organ coefficient in high-dose male group was higher than that in the male control group( P〈0. 05). Mild liver cell edemas were observed among the male and female exposed groups,but there were no statistical significant difference compared with the male and female control groups respectively( P〉0. 05
出处
《中国职业医学》
CAS
北大核心
2015年第3期286-291,共6页
China Occupational Medicine
基金
广东省职业病防治重点实验室(2012A061400007)
关键词
醚菌酯
亚慢性毒性
靶器官
经口毒性
剂量-效应关系
最大无作用剂量
肝脏
大鼠
Kresoxim-methyl
Sub-chronic toxicity
Target organ
Oral toxicity test
Dose-effect relationship
No observed adverse effect level
Liver
Rat