CENTRAL NERVOUS SYSTEM EFFECTS OF PCE EXPOSURE IN HUMANS

人类接触四氯乙烯对中枢神经系统的影响

• 批准号: 3420836
• 负责人: DIANA ECHEVERRIA
• 金额: $ 23.31万
• 依托单位: BATTELLE CENTERS/PUB HLTH RES & EVALUATN
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3420836
• 关键词: acute disease /disorder; air pollution; attention deficit disorder; brain stem; central nervous system disorders; centrally acting drug; chlorination; chronic disease /disorder; cognition disorders; drug administration rate /duration; ethylenes; evoked potentials; frontal lobe /cortex; hippocampus; human subject; hydropathy; industry; inhalation drug administration; limbic system; memory disorders; mood disorders; neurotoxins; occupational hazard; solvents

The proposed project will study the relationship between chronic exposure to perchloroethylene (PCE) and symptoms, neurobehavior, and neurophysiologic central nervous system (CNS) effects in workers. These effects will be evaluated in dry cleaners chronically exposed to different levels of PCE using never-exposed laundry workers as a reference group. Based on a pilot study, a frontal/limbic system behavioral hypothesis is offered for the site of underlying pathology for subclinical PCE effects. Alternatively, potential deficits could be related to hippocampus and brain-stem activity assessed separately by neurophysiologic electroencephalograms and visual evoked potentials. The cross-sectional CNS evaluation will be conducted on 84 never-exposed laundry workers, 42 low, 42 moderate, and 84 highly exposed dry cleaner employees in the Seattle, Washington area. To control for acute exposure effects, the symptom and behavioral evaluation will be conducted for 1 hour, 36 hours post-exposure at their work site. A pre-exposure alveolar breath sample will be measured to control for variation in PCE body burden, supplementing 8-hour air monitoring for each exposed and 1:8 non-exposed worker. Exposure zones will be based on (1) distance from PCE source, (2) PCE air levels, and (3) PCE breath levels. Peak sampling will be conducted on operators with fluctuating exposures estimated to affect brain PCE levels. These exposure measures will be used to construct lifetime indices of cumulative exposure. The 2-hour neurophysiologic assessment will occur at least 24 hours post-exposure a separate day. Paid volunteers will be 18 to 65 years old, English-speaking, and will have had no history of CNS disorders. No subjects will be excluded on the basis of alcohol consumption since interaction between PCE and alcohol is a research interest. The immediate influence of caffeine and alcohol will be controlled. To evaluate the exposure-effect within each shop, volunteers from each exposure zone will be tested. Potential confounding effects of age and education will be controlled by measures of stratification and multiple regression. To evaluate acute CNS effects, the high and the non-exposed group will be tested pre- and post-exposure. To estimate the degree of potential job selection bias in testing healthy workers, 42 previously exposed workers will also be followed-up from 10-year old employment rosters and evaluated for symptoms and behavioral effects. Completion of the proposed study would document a possible continuum from subclinical to clinical CNS effects following exposure to PCE in one of the few industrial populations frequently exposed to high levels above 40 ppm. The prevalence of chronic CNS effects would be described between 0 and 100 ppm, and the lower threshold for adverse symptoms, behavior, and physiologic effects would be known at the proposed OSHA PEL of 25 ppm.

拟议的项目将研究慢性接触之间的关系 与四氯乙烯(PCE)和症状、神经行为以及 工人的神经生理中枢神经系统(CNS)效应。这些 将对长期暴露在不同环境中的干洗店的影响进行评估 以从未接触过的洗衣工人为参照组的PCE水平。 基于一项初步研究，额叶/边缘系统的行为假说是 为亚临床PCE效应的潜在病理部位提供。 或者，潜在的缺陷可能与海马体和 用神经生理学方法分别评估脑干活动 脑电和视觉诱发电位。 将对84例未曝光的患者进行横断面CNS评价 洗衣房工人，42名低暴露干洗工，42名中等暴露干洗工，84名高度暴露于干洗店的工人 华盛顿州西雅图地区的员工。控制急性接触 效果，症状和行为评估将为1 在他们的工作场所暴露后1小时、36小时。暴露前的牙槽骨 呼气样本将被测量以控制PCE身体负荷的变化， 补充每个暴露者8小时空气监测和1：8未暴露者的空气监测 工人。曝光区将基于(1)到PCE源的距离，(2) PCE空气水平，以及(3)PCE呼吸水平。将进行峰值采样 关于估计会影响脑PCE的波动暴露的操作者 级别。这些暴露措施将被用于构建寿命指数 累积暴露的风险。将进行2小时的神经生理学评估 在另一天暴露后至少24小时。付费志愿者将年满18岁 至65岁，会说英语，并不会有中枢神经系统病史 精神错乱。不会因饮酒而排除任何受试者 因为四氯乙烯和酒精之间的相互作用是一个研究兴趣。这个 咖啡因和酒精的直接影响将受到控制。评估 每个商店内的曝光效果，来自每个曝光区的志愿者 将会受到考验。年龄和教育的潜在混杂影响将是 由分层和多元回归的措施控制。至 评估急性中枢神经系统效应，高暴露组和非暴露组将 在暴露前和暴露后进行测试。估计潜在工作的程度 在检测健康工人时存在选择偏差，42名既往接触过的工人 还将从10年前的就业花名册中进行跟踪和评估 症状和行为影响。 拟议研究的完成将记录一个可能的连续体， 接触PCE对临床中枢神经系统的亚临床影响 很少有工业人口经常暴露在高于40ppm的高水平下。 慢性中枢神经系统影响的患病率将被描述为0到100 Ppm，以及不良症状、行为和 在建议的25ppm的OSHA PEL时，生理效应是已知的。