Richardson R J, Moore T B, Kayyali U S, Fowke J H, Randall J C
Department of Environmental and Industrial Health, School of Public Health, University of Michigan, Ann Arbor 48109.
Fundam Appl Toxicol. 1993 Apr;20(3):273-9. doi: 10.1006/faat.1993.1036.
Chlorpyrifos (CPS; O,O-diethyl 3,5,6-trichloro-2-pyridyl phosphorothionate; Dursban) is a widely used broad-spectrum organophosphorus (OP) insecticide. Because some OP compounds can cause a sensory-motor distal axonopathy called OP compound-induced delayed neurotoxicity (OPIDN), CPS has been evaluated for this paralytic effect. Early studies of the neurotoxicity of CPS in young and adult hens reported reversible leg weakness but failed to detect OPIDN. More recently, a human case of mild OPIDN was reported to result from ingestion of a massive dose (about 300 mg/kg) in a suicide attempt. Subsequent experiments in adult hens (the currently accepted animal model of choice for studies of OPIDN) showed that doses of CPS in excess of the LD50 in atropine-treated animals inhibited brain neurotoxic esterase (NTE) and produced mild to moderate ataxia. Considering the extensive use of CPS and its demonstrated potential for causing OPIDN at supralethal doses, additional data are needed to enable quantitative estimates to be made of the neuropathic risk of this compound. Previous work has shown that the ability of OP insecticides to cause acute cholinergic toxicity versus OPIDN can be predicted from their relative tendency to inhibit the intended target, acetylcholinesterase (AChE), versus the putative neuropathic target, NTE, in brain tissue. The present study was designed to clarify the magnitude of neuropathic risk associated with CPS exposures by measuring hen brain AChE and NTE inhibition following dosing in vivo and determining the bimolecular rate constant of inhibition (ki) for each enzyme by the active metabolite, CPS oxon (CPO), in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
毒死蜱（CPS；O，O-二乙基 3,5,6-三氯-2-吡啶基硫代磷酸酯；敌百虫）是一种广泛使用的广谱有机磷杀虫剂。由于一些有机磷化合物可导致一种称为有机磷化合物诱发的迟发性神经毒性（OPIDN）的感觉运动性远端轴索性神经病，因此已对 CPS 的这种麻痹作用进行了评估。早期关于 CPS 对幼年和成年母鸡神经毒性的研究报告了可逆性腿部无力，但未检测到 OPIDN。最近，有报告称，一名人类患者因自杀企图摄入大量剂量（约 300 mg/kg）而导致轻度 OPIDN。随后在成年母鸡（目前被广泛接受的用于 OPIDN 研究的动物模型）身上进行的实验表明，在阿托品处理的动物中，超过半数致死剂量的 CPS 会抑制脑内神经毒性酯酶（NTE），并产生轻度至中度共济失调。鉴于 CPS 的广泛使用及其在超致死剂量下导致 OPIDN 的已证实潜力，需要更多数据来对该化合物的神经病变风险进行定量估计。先前的研究表明，有机磷杀虫剂导致急性胆碱能毒性与 OPIDN 的能力可根据它们在脑组织中抑制预期靶标乙酰胆碱酯酶（AChE）与假定的神经病变靶标 NTE 的相对倾向来预测。本研究旨在通过测量体内给药后母鸡脑内 AChE 和 NTE 的抑制情况，并在体外确定活性代谢物毒死蜱氧磷（CPO）对每种酶的抑制双分子速率常数（ki），来阐明与 CPS 暴露相关的神经病变风险程度。（摘要截取自 250 字）
