NEUROBEHAVIORAL PERFORMANCE INDICES AS BIOMARKERS OF PERCHLOROETHYLENE EXPOSURE

神经行为表现指数作为全氯乙烯暴露的生物标志物

• 批准号: 6296544
• 负责人: DIANA ECHEVERRIA
• 金额: $ 23.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296544
• 关键词: air sampling /monitoring; amine oxidase (flavin); attention; biomarker; breath tests; cognition; color visions; electroencephalography; environmental toxicology; evoked potentials; haloalkene; human subject; longitudinal human study; memory; nervous system disorder epidemiology; neurochemistry; neurophysiology; neuropsychological tests; neurotoxins; occupational disease /disorder; occupational hazard; psychomotor function; questionnaires; serotonin; sign /symptom

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.

本研究的目的是前瞻性评估 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，以及更客观的生理学 影响包括外周神经 (PNS)、自主神经 (ANS) 和感觉 (SNS) 神经系统反应。 我们整合了之间潜在的相互作用 乙醇消耗量和苯乙烯暴露量，适用于一般情况 人群，并评估单胺氧化酶-B (MaoB) 的使用，a 神经化学功能的外周血细胞标志物可能会改善 及早发现神经系统损伤。 长期目标是 建立一个测量临床前健康影响的范例 用于减少暴露时溶剂毒性的发生率和严重程度 低于 25 ppm，接近超级基金站点发现的水平。 我们的假设是，接触低于 25 ppm 的苯乙烯会产生不利影响 对神经系统功能的影响与强度和持续时间成正比 的曝光量。 在缺乏可防御的单一行动机制的情况下，我们 提出一种评估公认领域的系统方法 神经功能。 CNS 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） 洞察力。 PNS 域是 a) 神经完整性，b) 自主神经 小纤维副交感神经病变，c) 自主交感神经 长纤维神经病变，d) 有髓纤维神经病变，以及 e) 姿势摇摆和振动触觉敏感性的感官测试。 研究 将在华盛顿州普吉特海湾地区进行 36 ppm 范围在 0 到 147 ppm 之间。 完整的 68 名工人将被 扩大到162个科目。 此外，还有一个由 52 名新就业人员组成的小组 工人将接受测试并与更大的群体进行比较，提供个人资料 不适应溶剂的群体中最近的 CNS/PNS 效应。 这 乙醇对苯乙烯代谢的影响将在 实验室，结果将适用于行为研究。 此外，还将确定 MaoB 活动与 潜在的 CNS/PNS 效应强于直接测量的效应 剂量。 这是第一个大型后续研究，采用纵向重复研究 措施设计，将获得暴露效应的稳定估计 定义低于 25 ppm 的阈值限制所需的曲线，范围为 我们预计会出现神经阈值。 该设计还将 让我们能够区分与急性（日常）、亚慢性相关的影响 （一个月内）和慢性（几年内）苯乙烯 接触。 结果将有助于评估与低风险相关的风险 水平苯乙烯暴露，以及指导新的研究机制 行动。