农药混剂的选择毒性研究

稻瘟净或异稻瘟净与乐果或马拉松混用,对抗性黑尾叶蝉有明显的增效作用,对小白鼠急性口服毒性也有所增加。小白鼠口服稻瘟净或异稻瘟净后,鼠肝中水解乐果和N—甲基正己酰胺的羧酰胺酶活力明显下降;水解醋酸α-萘酯的羧酸酯酶活力也被抑制。羊肝微粒体的羧酰胺酶在体外分别被稻瘟净、异稻瘟净、磷酸三苯酯、磷酸三甲苯酯、苯硫磷、氧乐果和西维因强烈抑制,它们的I_(50)值为1.3×10~(-8)—4.0×10~(-5)克分子浓度。稻瘟净、异稻瘟净、磷酸三苯酯和西维因分别是羊肝羧酰胺酶和羧酸酯酶的竞争性抑制剂,它们的K_i值在4.8×10~(-8)—1.0×10~(-7)克分子浓度之间。这些结果表明稻瘟净、异稻瘟净等增加乐果和马拉松对哺乳动物的毒性的机制,可能主要是由于它们抑制了哺乳动物体内正常解毒乐果和马拉松的水解酶。文中讨论了这些农药混剂的选择毒性问题。

STUDIES ON THE SELECTIVE TOXICITY OF THE PESTICIDE MIXTURES

The acute oral toxicity of the mixtures of dimethoate or malathionwith EBP or IBP was determined in mice.The toxicity of dimethoate was enhanced 2.4 and 4.5 times respectively by IBP and EBP,and the toxicity of malathion was increased 5.5 times by EBP.The enzymatic hydrolysis of dimethoate,N-methylcaproamide and a-naphthylacetate by mice liver homogenates was strongly inhibitedafter oral treatment of mice with EBP or IBP.Almost complete inhibition of the carboxyamidase and the carboxylesterase occurred soonerafter a single oral dose of EBP(121 mg/kg)or IBP(343 mg/kg).The hydrolysis of dimethoate and N-methylcaproamide by the amidase of sheep liver microsomes in vitro was strongly inhibited by EBP,IBP triphenylphosphate(TPP),tri-ortho-tolylphosphate(TOCP),EPN,omethoate and carbaryl respectively.These inhibitors had lower I₅₀ values in the range 1.3×10^-8 to 4.0×10^-5 M.Tests showed that EBP,IBP,TPP and carbaryl were competitive inhibitors for both the carboxyamidase and the carboxylesterase of sheep liver microsomes.Inhibition constants (K_i) for these inhibitors ranged from 4.8×10^-8 to 1.0×10^-7 M.These results indicated that the synergistic mechanism for the above pesticide mixtures attributed mainly to EBP or IBP,which inhibited the detoxification normally occured by the hydrolysis of the carboxylamide linkage of dimethoate or the carboxylester linkage of malathion catalysed by the carboxyamidase or the carboxylesterase.