Menn J J, DeBaun J R, McBain J B
Fed Proc. 1976 Dec;35(14):2598-602.
Rat metabolism studies were conducted with three organophosphorus ester insecticides: [phenyl- or ethoxy-14C]Dyfonate, O-ethyl S-phenyl ethylphosphonodithioate; [phenyl-14C]Trithion, S-[(4-chlorophenylthio)methyl]O,O-diethylphosphorodithioate; and [phenyl-14C]R-14805, 4-[O,0-diethyl phosphorothioyl)]-acetophenoneoxime-N'-methylcarbamate. Compounds were administered orally to rats at 2 to 8 mg/kg, and biotransformation pathways were established from identified metabolites. Metabolites were isolated from O-96 hr urine and identified by using one or more methods including thin-layer chromatography, radio-gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance. Each of these model insecticides displayed a distinct bioactivation and detoxification pathway. Conversion to potent acetylcholinesterase inhibitors resulted from desulfuration of Dyfonate, desulfuration and thioether oxidation of Trithion, and desulfuration and a variety of modifications of the leaving group of R-14805. The compounds were deactivated primarily via cleavage of an organophosphorus ester group. All three compounds and their metabolites were rapidly excreted primarily in urine without any bioaccumulation in tissues.
[苯基 - 或乙氧基 - ¹⁴C]地虫硫磷，O - 乙基 - S - 苯基乙硫代磷酰二硫酯；[苯基 - ¹⁴C]三硫磷，S - [(4 - 氯苯基硫代)甲基]O,O - 二乙基硫代磷酰二硫酯；以及[苯基 - ¹⁴C]R - 14805，4 - [O,O - 二乙基硫代磷酰基)] - 苯乙酮肟 - N'- 甲基氨基甲酸酯。以2至8毫克/千克的剂量给大鼠口服这些化合物，并根据鉴定出的代谢产物确定生物转化途径。从0至96小时的尿液中分离出代谢产物，并使用一种或多种方法进行鉴定，包括薄层色谱法、放射性气液色谱法、质谱法和核磁共振法。每种这类典型杀虫剂都显示出独特的生物活化和解毒途径。地虫硫磷的脱硫、三硫磷的脱硫和硫醚氧化以及R - 14805离去基团的脱硫和各种修饰导致了向强效乙酰胆碱酯酶抑制剂的转化。这些化合物主要通过有机磷酸酯基团的裂解而失活。所有这三种化合物及其代谢产物主要迅速经尿液排出，在组织中无任何生物蓄积。
