TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

这项建议的长期目标是提供信息 这将有助于确定在哪些情况下 个体可能对有机硫磷杀虫剂敏感- 诱导毒性。它寻求通过以下方式实现这一目标 确定肝和肝外的相对作用 这些化学物质在介导其急性毒性反应中的生物转化 毒物。在这种方法中隐含的是对 影响这些关键代谢途径的因素很多。 预计这些研究将提供有用的信息。 在评估有机硫磷对健康的危害时 杀虫剂及其有毒相互作用的可能性 和某些其他的有生菌。此外，这些研究将 有助于了解这些代谢系统的基本知识 参与有机硫代磷酸盐的生物转化 杀虫剂。这项研究要解决的具体目标 具体如下：1.进一步调查是否含有有毒物质 由有机硫代磷酸盐在肝内生产氧气类似物 杀虫剂进入一般循环，或者它们是否经历了 广泛的肝内排毒，从而防止他们 从肝脏中逃逸。2.检测血液中的A-酯酶 有能力阻止这些恶臭生物逃脱 肝脏以脑和肺等组织为靶标。3.至 探讨其对肝外的毒理学意义 某些有机硫磷杀虫剂的激活。4.至 确定和表征代谢激活和 有机硫磷杀虫剂的人体解毒作用 胎盘。5.评估谷胱甘肽介导的作用 二甲基硫代磷酸盐的生物转化研究 体内对这些农药有解毒作用。

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.