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: 6106158
• 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/6106158
• 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地评价 暴露于苯乙烯的症状、情绪和行为， 中枢神经系统（CNS）功能，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。 我们将潜在的相互作用， 乙醇消耗和苯乙烯暴露，适用于一般 人口，并评估使用单胺氧化酶-B（MaoB）， 外周血细胞神经化学功能标志物，可改善 神经系统损伤的早期检测。 长期目标是 建立一个测量临床前健康影响的范例， 用于降低暴露时溶剂毒性的发生率和严重程度 低于百万分之25，接近超级基金所在地的水平。 我们的假设是，接触苯乙烯低于25 ppm 影响神经系统功能的强度和持续时间成正比 暴露。 在缺乏可辩护的单一作用机制的情况下，我们 提出一个系统的方法，评估公认的领域， 神经功能 CNS领域包括：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） perception. PNS结构域是a）神经完整性，B）自主神经功能， 小纤维副交感神经病，c）自主交感神经 长纤维神经病，d）有髓纤维神经病，和e） 姿势摇摆和振动触觉灵敏度的感觉测试。 研究 将在华盛顿州的普吉湾地区进行， ppm在0和147 ppm之间。 完整的68名工人将被 扩展到162个主题。 此外，一个由52名新雇员组成的小组 工人将进行测试，并与较大的群体进行比较， 最近CNS/PNS的影响在不适应溶剂的群体中。 的 乙醇对苯乙烯代谢的影响将在 实验室和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 次给药结束 这是第一个大的后续研究，采用纵向重复 措施的设计，这将获得稳定的估计， 定义低于25 ppm的阈值极限所需的曲线， 这是我们所期望的神经学阈值。 该设计还将 使我们能够区分与急性（每日）、亚慢性 (over一个月的时间）和慢性（几年的时间）苯乙烯 exposure. 这些结果将有助于评估与低血糖相关的风险。 水平的苯乙烯暴露，以及指导新的研究机制， 行动上