TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

该项目的长期目标是提供信息，以便 协助确定个人可能在何种情况下 易受有机硫磷农药中毒的影响。它寻求 通过专注于肝和肝外 这些农药的代谢活化和解毒调节了它们的 毒性。相对活化和解毒作用 有机硫磷农药在入境点和在吸收后，在 不同的内脏器官会极大地影响病情的严重程度和时间。 它们的毒性过程。了解其他外国公司的互动 具有不同暴露途径的有机硫磷化合物 需要了解这些杀虫剂的代谢关系 通过不同的组织。这项研究不仅将提供信息 有助于农药的安全评估，但也将有助于 这些新陈代谢系统的基础知识 这些杀虫剂的生物转化。要解决的具体目标 本研究的主要内容是：1.评价有毒氧类似物是否产生 从肝脏中从有机硫磷逃逸到肝脏，从而进入 全身循环，或者这些是有效的胆碱酯酶抑制剂 进一步在肝脏中生物转化，在它们离开之前灭活它们 肝脏；2.如果有机硫代磷酸盐的有毒氧类似物逃脱 肝脏并进入血液，它们能存活足够长的时间到达 肝外器官，还是会很快被血浆解毒 A-酯酶；3.评价肝外毒素的毒理学意义 有机硫磷农药的活化，特别强调 大脑。

The long-term objective of this project 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 focusing on how hepatic and extrahepatic metabolic activation and detoxification of these pesticides mediate their toxicity. The relative activation and detoxification of organothiophosphate pesticides at sites of entry and, after absorption, at various internal organs could greatly influence the severity and time course of their toxicity. Understanding the interactions of other foreign compounds with organothiophosphates following different routes of exposure requires knowledge of the relationships of metabolism of these pesticides by different tissues. This research will not only provide information helpful in the safety assessment of pesticides, but will also contribute to the fundamental knowledge of those metabolic systems involved in the biotransformation of these pesticides. Specific aims to be addressed in this research are: 1. To evaluate if the toxic oxygen analogs produced hepatically from organothiophosphates escape the liver, thereby entering the general circulation, or are these potent cholinesterase inhibitors further biotransformed hepatically, inactivating them before they exit the liver; 2. If the toxic oxygen analogs of organothiophosphates escape the liver and enter the blood, can they survive long enough to reach extrahepatic organs, or will they quickly be detoxified by plasma A-esterases; 3. To evaluate the toxicological significance of extrahepatic activation of organothiophosphate pesticides with particular emphasis on the brain.