Clean Air Act Neurotoxicity Studies and NTP/NIEHS Neuropathology Evaluations

在过去十年中，公众和科学对慢性神经退行性疾病的认识大幅提高，最近随着知名个人披露其神经系统疾病及其与环境化学品的潜在联系，认识达到了历史最高水平。其中一个令人担忧的问题是，清洁空气行动化学品二硫化碳和羰基硫化物以及其他环境制剂的潜在神经毒性。其目标是提供关于二硫化碳(CS2)或其他环境化学品如何影响人类健康的更好的机械数据。第二个目标是确定羰基硫化物或其他环境化学品是否有可能导致神经毒性。由于羰基硫化物是二硫化碳的代谢物，另一个目的是比较羰基硫化物和二硫化碳的毒性机理。另一个目标是在神经毒性研究期间提供神经系统完整性的详细描述。神经毒性指南的一个共同主题是，所有可用的数据都应该整合起来，以提供对任何可能的神经毒性危害的连贯描述。这一综合图景受到负责评估和管理与复杂神经系统相关的风险的监管机构的高度重视。评估需要整合来自行为、电生理、生化和病理终点的数据。研究正在通过内部动物研究完成，并通过合作努力继续进行。方法是进行一项综合的内部吸入毒性研究，包括毒代动力学、行为、电生理和病理终点，检查剂量反应关系和潜在的毒性机制。然后，这些研究的信息将被用于计划更长期的研究，并修改正在进行的研究，以进行全面的神经病理学评估。

Public and scientific awareness of chronic neurodegenerative disease has risen dramatically during the last decade and recently reached an all time high with the disclosure by well-known individuals of their nervous system maladies and the potential association with environmental chemicals. Among the concern, is the potential neurotoxicity of the clean air act chemicals carbon disulfide and carbonyl sulfide and other environmental agents. The goal is to provide better mechanistic data on how carbon disulfide (CS2) or other environmental chemicals can affect human health. A second goal is to determine whether carbonyl sulfide or other environmental chemicals have the potential to cause neurotoxicity. Since carbonyl sulfide is a metabolite of carbon disulfide, another goal is to compare the mechanism of toxicity of carbonyl sulfide with that of carbon disulfide. A further goal is to provide detailed descriptions of the nervous system integrity during neurotoxicity studies. A common theme among neurotoxicity guidelines is that all available data should be integrated to provide a coherent description of any possible neurotoxic hazards. This integrated picture is valued highly by regulators who have the responsibility for assessing and managing risk connected with the complex nervous system. The assessment requires integration of data from behavioral, electrophysiological, biochemical and pathological endpoints. Research is being accomplished through in-house animal studies and is being continued through collaborative efforts. The approach is to conduct an integrated in-house inhalation toxicity study which will include toxicokinetic, behavioral, electrophysiological and pathological end points, examining dose response relationships and potential mechanisms of toxicity. Information from these studies will then be used to plan longer term studies and modify ongoing studies for comprehensive neuropathology assessments.