ORGANOPHOSPHORUS INSECTICIDE TOXICOLOGY

描述（改编自研究者摘要）：长期 目的是了解急性和迟发毒性的机制 重要的有机磷（OP）和膦杀虫剂。 这些 化合物是人类健康的主要关注点，因为它们广泛用于 农业和负责更多的中毒案件比任何其他 杀虫剂类 目的一是明确OP诱导迟发毒性的机制 （已折磨超过30，000人）与神经病有关 靶向酯酶（NTE）使用我们新开发的放射性配体[3 H]OBDPO和 用于从鸡脑中靶向分离的新型氨基甲酸酯-生物素亲和剂 结构和功能表征的活性形式。 非新界东目标 通过[3 H]OBDPO和基于其他OP延迟的放射性配体磷酸化 有毒物质将通过NTE本身进行识别。 细胞模型将 确定OP诱导的神经生长变化，必需的神经营养因子 和离子运输。 第二个目的是了解重要OP杀虫剂的作用机制 因为它对植物有内吸作用，对哺乳动物有中等毒性。 的 假设是：乙酰甲胺磷毒性是自限性的，因为其代谢物 甲胺磷抑制激活乙酰甲胺磷的酰胺酶;甲胺磷 通过S-氧化（旧假设）或N-氧化（新提议）生物活化 需要化学模型的研究来解决网站和稳定性 关系;二甲基二硫代磷酸的S-甲基化作为 乐果代谢物有助于其毒理学特征，包括 延迟效应。 第三个目的是建立铝的毒性机制 磷化物正逐渐取代甲基溴（臭氧 消耗剂）作为储存产品的主要熏蒸剂。 总体假设 是1）磷化氢，一种在环境水解时释放气体， 磷化铝，经历自发或生物氧化， 氧化膦，和2）这种膦化剂产生急性毒性 对尚未确定的靶点的作用和对衍生DNA的遗传毒性作用 导致脱氧鸟苷部分转化为 8-羟基脱氧鸟苷。 为了确保安全使用， 含磷杀虫剂。

DESCRIPTION (Adapted from the Investigator's Abstract): The long-term objective is to understand the mechanisms for acute and delayed toxicity from important organophosphorous (OP) and phosphine insecticides. These compounds are major concerns for human health since they are widely used in agriculture and responsible for more cases of poisoning than any other pesticide class. The first aim is to define the mechanisms of OP-induced delayed toxicity (which has afflicted greater than 30,000 people) associated with neuropathy target esterase (NTE) using our newly-developed radioligand [3H]OBDPO and a novel carbamate-biotin affinity agent for target isolation from hen brain in active form of structural and functional characterization. Non-NTE targets phosphorylated by [3H]OBDPO and radioligands based on other OP delayed toxicants will be identified as with NTE itself. Cellular models will determine OP-induced changes in neural growth, essential neurotropic factors and ion transport. The second aim is to understand the mechanisms of important OP insecticides because of systemic action in plants and moderate toxicity to mammals. The hypotheses are: acephate toxicity is self-limiting because its metabolite methamidophos inhibits the amidase that activates acephate; methamidophos is bioactivated by S-oxidation (old hypothesis) or N-oxidation (new proposal) requiring studies of chemical models to resolve the site and stability relationships; S-methylation of dimethyl phosphorodithioic acid as a dimethoate metabolite contributes to its toxicological profile including delayed effects. The third aim is to establish the mechanisms for toxicity of aluminum phosphide which is increasingly replacing methyl bromide (the ozone depleter) as the major fumigant for stored products. The overall hypothesis is that 1) phosphine, a gas liberated on environmental hydrolysis of aluminum phosphide, undergoes spontaneous or biological oxidation to phosphine oxide, and 2) this phosphinylating agent produces acute toxic effects at a yet undefined target and genotoxic effects on derivatizing DNA leading to conversion of the deoxyguanosine moiety to 8-hydroxydeoxyguanosine. This research is necessary to ensure the safe use of phosphorus-containing insecticides.