TOXICOLOGICAL SIGNIFICANCE OF PESTICIDE METABOLISM

农药代谢的毒理学意义

• 批准号: 3252430
• 负责人: LESTER G SULTATOS
• 金额: $ 13.03万
• 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 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3252430
• 关键词: autoradiography; biotransformation; brain; cholinesterase inhibitors; cytochrome P450; detoxification; drug administration routes; environmental toxicology; enzyme mechanism; esterase; gastrointestinal toxin absorption; glutathione; high performance liquid chromatography; human tissue; laboratory mouse; laboratory rat; liver circulation; liver metabolism; molecular site; organ; organophosphorus insecticide; parathion; pesticide interaction; radiotracer; respiratory oxygen; scintillation counter; thin layer chromatography; toxicant interaction

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.

该提案的长期目标是提供信息 这将有助于确定条件 个体可能容易受到有机磷酸磷酸盐农药的影响 - 诱导的毒性。 它试图通过 确定肝和肝外的相对角色 这些化学物质的生物转化在介导其急性中 有毒剂。 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 评估有机磷酸盐的健康危害 杀虫剂及其有毒相互作用的潜力 与某些其他沸点。 此外，这些研究将 有助于这些代谢系统的基本知识 参与有机噬员的生物转化 杀虫剂。 在这项研究中要解决的具体目标 如下：1。进一步研究有毒 从有机磷酸盐内部产生的氧气类似物 农药进入一般流通，或者是否经历 广泛的肝内排毒，从而阻止了他们的 逃离肝脏。 2。确定血液中的A-撒酯酶是否 有能力防止那些牛的逃脱 肝脏靶向组织，例如大脑和肺部。 3 研究对肝外的毒理学意义 某些有机磷酸杀虫剂的激活。 4 识别和表征代谢激活和 人类的有机磷酸杀虫剂的排毒 胎盘。 5。评估Gluthathione介导的作用 二甲基取代的有机磷酸酯中的生物转化 这些农药排毒的体内。