醚菌酯原药大鼠慢性毒性与致癌性试验

Experimental study on the chronic toxicity and carcinogenicity of kresoxim-methyl in rats

目的探讨醚菌酯原药对大鼠的慢性毒性作用和致癌作用。方法无特定病原体级SD大鼠按体质量随机分为对照组和低、中、高剂量组,每组各120只,雌雄各半。采用饲喂法对大鼠进行104周的慢性毒性与致癌合并试验,雌、雄性4组大鼠饲料中醚菌酯原药质量分数分别为0、75、300、1200 mg/kg。实验期间称量大鼠体质量,于染毒结束时进行血生化、脏器系数和组织病理学检查,并计算肿瘤发生率。结果雌性或雄性4组大鼠死亡率分别比较,差异均无统计学意义(P>0.05)。染毒第32、48、56周,高剂量组雌性大鼠体质量分别低于同时间点对照组(P<0.05);染毒第8、16、24、32周,高剂量组雄性大鼠体质量分别低于同时间点对照组(P<0.05)。高剂量组雌性大鼠心脏、肾上腺脏器系数分别高于对照组和低剂量组(P<0.05);高剂量组雄性大鼠肝脏脏器系数低于对照组(P<0.05)。3个剂量组雄性大鼠的碱性磷酸酶活力分别低于对照组(P<0.05)。与对照组比较,高剂量组雄性大鼠的血糖水平升高(P<0.05),天冬氨酸氨基转移酶活力降低(P<0.05)。上述3个指标在雌性4组大鼠中分别比较,差异均无统计学意义(P>0.05)。对照组和低、中、高剂量组大鼠肿瘤发生率分别为68.3%、75.0%、75.0%、78.8%,差异无统计学意义(P>0.05)。雌性大鼠肿瘤发生率高于雄性大鼠(87.0%vs 61.5%,P<0.01)。4组大鼠肿瘤多发率分别为38.3%、35.8%、35.0%、39.8%,差异无统计学意义(P>0.05);雌性大鼠肿瘤多发率高于雄性大鼠(56.9%vs 17.6%,P<0.01)。结论醚菌酯原药对雌、雄性SD大鼠慢性毒性的最大无作用剂量分别为24.726和20.002 mg/(kg·d);未见醚菌酯原药对SD大鼠具有致癌作用。

Objective To investigate the chronic toxicity and carcinogenicity of kresoxim-methyl in rats.Methods Specific pathogen free SD rats were randomly divided into control group and low-,medium-and high-dose groups according to the body weight of rats,120 rats in each group with half male and half female rats.The chronic toxicity and carcinogenesis was induced in rats for 104 weeks by oral feeding.The dose of kresoxim-methyl in feed of male and female rats was 0,75,300 and 1200 mg/kg.During the process of experiment,the body weight of rats was weighed.The blood biochemistry,organ coefficient and histopathology were examined at the end of the exposure,and the tumor incidence was calculated.Results There was no significant difference in mortality of the female or male rats in the four groups(P>0.05).At the 32nd,48th and 56th week after exposure,the body mass of female rats in the high dose group was lower than that in control group(P<0.05);at the 8th,16th,24th and 32nd week,the body mass of male rats in the high dose group was lower than that in the control group(P<0.05).The organ coefficients of heart and adrenal gland of female rats in the high dose group were higher than those in the control group and the low dose group(P<0.05).The organ coefficient of liver of male rats in the high dose group was lower than that in the control group(P<0.05).The alkaline phosphatase of male rats in the three dose groups was lower than that in the control group(P<0.05).The blood glucose of male rats in the high dose group was higher than that in the control group(P<0.05).The aspartate aminotransferase of male rats in the high dose group was lower than that in the control group(P<0.05).There was no significant difference among the three indexes in female rats(P>0.05).The tumor incidence of the control group and the low,medium and high dose groups were 68.3%,75.0%,75.0%and 78.8%,respectively,with no significant difference(P>0.05).The tumor incidence of the female rats was higher than that of the male rats(87.0%vs 61.5%,P<0.01).The tumor multiplicity of the above four groups were 38.3%,35.8%,35.0%,39.8%,respectively,with no significant difference(P>0.05).The tumor multiplicity in female rats was higher than that in male rats(56.9%vs 17.6%,P<0.01).Conclusion The no observed adverse effect level of kresoxim-methyl to female and male SD rats was 24.726 and 20.002 mg/(kg·d),respectively.No carcinogenicity of kresoxim-methyl to SD rats was observed.