NEUROBEHAVIORAL PERFORMANCE INDICES AS BIOMARKERS OF PERCHLOROETHYLENE EXPOSURE

这项研究的目的是前瞻性地评估 接触苯乙烯对症状、情绪和行为的影响 中枢神经系统(CNS)功能，以及更客观的生理 影响包括外周(PNS)、自主神经(ANS)和感觉(SNS) 神经系统反应。我们结合了潜在的相互作用 酒精消耗量和苯乙烯暴露量，适用于一般 种群，并评估单胺氧化酶-B(MAOB)的使用，a 可能改善神经化学功能的外周血细胞标志物 早期发现神经系统损害。长期目标是 建立一个衡量临床前健康影响的范例，可以 用于降低暴露时溶剂中毒的发生率和严重程度 低于25ppm，接近超级基金网站的水平。 我们的假设是，暴露在低于25ppm的苯乙烯中对人体有害 影响神经系统功能与强度和持续时间成正比 曝光率。在缺乏可辩护的单一行动机制的情况下，我们 提出一种系统的方法来评估公认的领域 神经功能。中枢神经系统域是：a)主观反应，b) 认知灵活性和推理，c)信息处理，d)运动 速度、灵活性和震颤，e)注意力，f)编码，g)视觉记忆，h) 感知力。三叉神经节结构域是a)神经完整性，b)自主 小纤维中的副交感神经病，c)自主交感神经 长纤维神经病，d)有髓纤维神经病，e) 姿势摆动和振动触觉敏感度的感觉测试。这项研究 将在华盛顿州的普吉特湾地区进行 Ppm在0到147 ppm之间。由68名工人组成的完整小组将是 扩大到162名受试者。此外，由52名新就业人员组成的小组 员工将接受测试，并与更大的群体进行比较，提供一份个人资料 在不适应该溶剂的组中，最近CNS/PNS的影响。这个 乙醇对苯乙烯代谢的影响将在一个 实验结果将适用于行为学研究。 此外，还将确定MAOB活动和 潜在的CNS/PNS效应强于直接测量 剂量。 这是第一次大规模的跟踪研究，采用了纵向重复研究 措施设计，将获得对暴露影响的稳定估计 定义低于25ppm的阈值限制所需的曲线，范围为 我们预计会出现神经学阈值。该设计还将 使我们能够区分急性(每日)、亚慢性 (一个月内)和慢性(数年内) 曝光。研究结果将有助于评估与低血压相关的风险。 水平的苯乙烯暴露，以及指导对 行动。

The objective of this study is to evaluate prospectively the effects of exposure to styrene with respect to symptoms, mood, and behavior reflecting central nervous system (CNS) functions, and more objective physiologic effects including peripheral (PNS), autonomic (ANS), and sensory (SNS) nervous system responses. We incorporate the potential interaction between ethanol consumption and styrene exposure, applicable to the general population, and evaluate the use of monoamine oxidase-B (MaoB), a peripheral blood cell marker of neurochemical function which may improve early detection of nervous system impairment. The long-term goal is to establish a paradigm for measuring preclinical health effects that can be used to reduce the incidence and severity of solvent toxicity, at exposures below 25 ppm approaching levels found at superfund sites. Our hypothesis is that exposure to styrene less than 25 ppm adversely effects nervous system functions proportional to the intensity and duration of exposure. In the absence of a defensible single mechanism of action, we propose a systematic approach which evaluates recognized domains of neurologic function. The CNS domains are; a) subjective responses, b) cognitive flexibility and reasoning, c) information processing, d) motor speed, dexterity, and tremor, e)attention, f) coding, g) visual memory, h) perception. The PNS domains are a) nerve integrity, b) autonomic parasympathetic neuropathy in small fibers, c) autonomic sympathetic neuropathy in long fibers, d) neuropathy in myelinated fibers, and e) sensory tests of postural sway and vibrotactile sensitivity. The study will be conducted in the Puget Sound Area of Washington State among was 36 ppm ranging between 0 and 147 ppm. The intact group of 68 workers will be expanded to 162 subjects. In addition, a sub-group of 52 newly employed workers will tested and compared to the larger group, providing a profile of recent CNS/PNS effects among the group unadapted to the solvent. The influence of ethanol on styrene metabolism will be conducted in a laboratory and the results will be applicable to the behavioral study. Also it will be determined if the association between MaoB activity and potential CNS/PNS effects are stronger than that for direct measures of dose. This is the first large follow-up study, employing a longitudinal repeated measures design, that will obtain stable estimates of exposure-effect curves necessary to define a threshold limit below 25 ppm, the range in which we expect neurologic threshold values to occur. The design will also allow us to distinguish effects associated with acute (daily), sub-chronic (over a period of a month), and chronic (over a period of years) styrene exposure. The results will be useful in assessing risk associated with low level styrene exposure, as well as guiding new research into mechanisms of action.