TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

农药代谢的毒理学意义

• 批准号: 3252432
• 负责人: LESTER G SULTATOS
• 金额: $ 6.55万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3252432
• 关键词: autoradiography; biotransformation; brain; cholinesterase inhibitors; cytochrome P450; detoxification; drug administration routes; environmental toxicology; esterase; gastrointestinal toxin absorption; high performance liquid chromatography; liver circulation; liver metabolism; molecular site; organ; organophosphorus insecticide; parathion; pesticide interaction; radiotracer; respiratory oxygen; scintillation counter; thin layer chromatography

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.

该项目的长期目标是提供信息 协助确定个人可能处于的条件 容易受到有机磷酸农药诱导的毒性的影响。 它试图 通过关注肝和肝外的方式来实现这一目标 这些农药的代谢激活和排毒介导了它们 毒性。 相对激活和排毒的 有机健康磷酸盐农药在入境部位和吸收后，在 各种内部器官可能会极大地影响严重性和时间 它们的毒性。 了解其他外国的互动 遵循不同暴露途径的有机壳磷酸盐的化合物 需要了解这些农药的代谢关系 通过不同的组织。 这项研究不仅将提供信息 有助于对农药的安全评估，但也将有助于 涉及的那些代谢系统的基本知识 这些农药的生物转化。 具体目的要解决 这项研究是：1。评估是否产生了有毒氧类似物 来自有机磷酸盐的肝脏逃脱肝脏，从而进入 一般循环，或这些有效的胆碱酯酶抑制剂 进一步的生物转化是肝脏的，在他们退出之前将它们灭活 肝; 2。如果有机壳的有毒氧类似物逃脱 肝脏进入血液，可以生存足够长的时间以至于到达 肝外器官，否则它们会很快被血浆解毒 A-撒酶； 3。评估肝外毒理学的毒理学意义 有机硫化磷酸盐农药的激活，特别强调 大脑。