TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

该项目的长期目标是提供信息， 协助确定个人可能被剥夺自由的条件 易受有机硫代磷酸酯农药诱导毒性的影响。 它寻求 通过关注肝和肝外 这些农药的代谢活化和解毒介导它们的 毒性 相对激活和解毒 有机硫代磷酸酯农药在入境地点和吸收后，在 内脏器官的变化对损伤的严重程度和时间有很大影响 其毒性的过程。 了解其他外国人的相互作用 通过不同途径接触有机硫代磷酸酯的化合物 需要了解这些农药的代谢关系 不同的组织。 这项研究不仅能提供信息， 有助于农药的安全评估，但也有助于 这些代谢系统的基本知识参与了 这些农药的生物转化。 具体目标 本研究的主要内容是：1.为了评估有毒的氧类似物是否产生 肝从有机硫代磷酸盐逃逸肝脏，从而进入 还是这些强效的胆碱酯酶抑制剂 进一步生物转化肝，灭活他们之前，他们离开 肝脏; 2.如果有机硫代磷酸酯的有毒氧类似物逸出， 肝脏并进入血液，它们能存活足够长的时间， 肝外器官，或将他们迅速解毒血浆 A-酯酶; 3.目的：评价肝外给药的毒理学意义 有机硫代磷酸盐农药的活化， 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.