Brown M A, Brix K A
Center for Science in the Public Interest, Washington, DC, USA.
J Appl Toxicol. 1998 Nov-Dec;18(6):393-408. doi: 10.1002/(sici)1099-1263(199811/12)18:6<393::aid-jat528>3.0.co;2-0.
Short and long-term health effects from exposure to organophosphorus (OP) military and insecticidal nerve agents are evaluated based on the abundant scientific literature published over five decades on health effects in humans (from human experimentation and occupational exposures) and in laboratory animals. Four distinct health effects are identified: acute cholinergic toxicity; organophosphate-induced delayed neuropathy (OPIDN); subtle long-term neuropsychological and neurophysiological effects; and a reversible muscular weakness called 'intermediate syndrome'. Some effects are subtle and difficult to differentiate from health effects caused by other diseases or occupational exposures. Each effect has data suggesting threshold exposure levels below which it is unlikely to be clinically detectable. Therefore, meaningful interpretation of human and animal studies requires rigid exposure characterization. Because precise exposure levels are often difficult to reconstruct, a system for characterizing exposure is proposed based upon observed initial acute signs and symptoms, as high-level (definitive cholinergic poisoning); intermediate-level (threshold cholinergic effects including miosis, rhinorrhea or clinically measurable depression of cholinesterase); and low-level (no immediate clinical signs or symptoms) exposure. Threshold exposure levels for known long-term effects from OP nerve agent are at or above intermediate-level exposure. Long-term health effects seen at intermediate-level exposures or in many survivors of high-level exposure are subtle, detectable in exposed populations but not individuals, and not reported in individuals experiencing low-level exposure alone. Co-exposure to other pharmaceutical agents may promote or protect against health effects from OP nerve agents, but qualitatively they are the same effects seen with OP nerve agents alone. Thus, the system for characterizing exposure based on initial acute effects is also useful for evaluating health outcomes from co-exposure to OP nerve and other agents.
基于五十多年来发表的关于人类（来自人体实验和职业暴露）及实验动物健康影响的丰富科学文献，对接触有机磷（OP）军用和杀虫神经毒剂的短期和长期健康影响进行了评估。确定了四种不同的健康影响：急性胆碱能毒性；有机磷诱导的迟发性神经病（OPIDN）；细微的长期神经心理和神经生理影响；以及一种称为“中间综合征”的可逆性肌无力。有些影响很细微，难以与其他疾病或职业暴露引起的健康影响区分开来。每种影响都有数据表明存在阈暴露水平，低于该水平临床上不太可能检测到。因此，对人类和动物研究进行有意义的解释需要严格的暴露特征描述。由于精确的暴露水平往往难以重建，因此基于观察到的初始急性体征和症状，提出了一种暴露特征描述系统，即高水平（明确的胆碱能中毒）；中间水平（阈胆碱能效应，包括瞳孔缩小、流涕或临床上可测量的胆碱酯酶抑制）；以及低水平（无即时临床体征或症状）暴露。已知OP神经毒剂长期影响的阈暴露水平处于或高于中间水平暴露。在中间水平暴露者或许多高水平暴露幸存者中观察到的长期健康影响很细微，在暴露人群中可检测到，但在个体中检测不到，并且仅经历低水平暴露的个体中未报告。同时接触其他药剂可能会促进或预防OP神经毒剂的健康影响，但从性质上讲，它们与单独接触OP神经毒剂时看到的影响相同。因此，基于初始急性效应的暴露特征描述系统也有助于评估同时接触OP神经毒剂和其他药剂的健康结果。
