TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

这项建议的长期目标是提供信息， 这将有助于确定 个别人士可能对有机硫代磷酸盐杀虫剂敏感， 诱导毒性。 它力求通过以下方式实现这一目标： 确定肝和肝外的相对作用 这些化学物质的生物转化， 毒性 在这种方法中隐含的是评估 影响这些关键代谢途径的许多因素。 预计这些研究将提供有用的信息， 在评估有机硫代磷酸盐对健康的危害时， 杀虫剂及其潜在的毒性相互作用 和其他益生菌混合 此外，这些研究将 有助于了解这些代谢系统的基础知识， 参与有机硫代磷酸酯的生物转化 杀虫剂 本研究要解决的具体目标 如下：1. 为了进一步调查是否有毒 从有机硫代磷酸盐肝内产生的氧类似物 农药进入一般流通，或是否经过 广泛的肝内解毒，从而防止他们 从肝脏中逃脱。 2.为了确定血液中的A酯酶 有能力阻止这些oxons逃逸 肝脏转移到脑和肺等靶组织。 3. 到 探讨肝外给药的毒理学意义 某些有机硫代磷酸酯杀虫剂的活化。4. 到 识别和表征代谢活化， 有机硫代磷酸酯杀虫剂的人体解毒作用 胎盘 5.评估谷胱甘肽介导的 二甲基取代的有机硫代磷酸酯的生物转化 在体内对这些杀虫剂进行解毒。

The long-term objective of this proposal is to supply information which will aid in the identification of conditions under which individuals might be susceptible to organothiophosphate pesticide- induced toxicity. It seeks to accomplish this objective by determining the relative roles of hepatic and extrahepatic biotransformation of these chemicals in mediating their acute toxcicities. Implicit in this approach is the evaluation of numerous factors which affect these critical metabolic pathways. It is expected that these studies will provide information useful in assessing the health hazards of organothiophosphate insecticides, as well as their potential for toxic interactions with certain other zenobiotics. Furthermore these studies will contribute to the fundamental knowledge of those metabolic systems involved in the biotransformation of organothiophosophate insecticides. The specific aims to be addressed in this research are as follows: 1. To further investigate whether the toxic oxygen analogs produced intrahepatically from organothiophosphate pesticides enter the general circulation, or whether they undergo extensive intrahepatic detoxification thereby preventing their escape from the liver. 2. To determine if the A-esterase in blood has the capacity to prevent the passage of those oxons escaping liver to target tissues such as brains and lungs. 3. To investigate the toxicological significance to extrahepatic activation of certain organothiophosphate insecticides. 4. To identify and characterize the metabolic activation and detoxification of organothiophosphate insecticides by human placenta. 5. To evaluate the role of gluthathione-mediated biotransformation of dimethyl-substituted organothiophosphates in vivo in the detoxification of these pesticides.