CENTRAL NERVOUS SYSTEM EFFECTS OF PCE EXPOSURE IN HUMANS

拟议的项目将研究长期接触 四氯乙烯（PCE）和症状，神经行为， 中枢神经系统（CNS）的影响。这些 影响将评估干洗店长期暴露于不同的 使用从未接触过的洗衣工人作为参照组的四氯乙烯水平。 基于一项初步研究，一个额叶/边缘系统行为假设是 为亚临床PCE效应的基础病理部位提供。 或者，潜在的缺陷可能与海马和 通过神经生理学单独评估脑干活动 脑电图和视觉诱发电位。 将对84名从未暴露过的患者进行横断面CNS评价。 洗衣工人、42名低暴露、42名中等暴露和84名高度暴露的干洗工 西雅图和华盛顿地区的雇员。控制急性暴露 效果，将进行症状和行为评价， 在他们的工作场所暴露后36小时。暴露前肺泡 将测量呼吸样本以控制PCE身体负荷的变化， 对每个暴露者和1：8非暴露者补充8小时空气监测 worker.暴露区域将基于（1）与PCE源的距离，（2） PCE空气水平，和（3）PCE呼吸水平。将进行峰值采样 暴露量波动估计会影响大脑PCE的操作员 程度.这些暴露量将用于构建寿命指数 累积暴露。将进行2小时神经生理学评估 至少在暴露后24小时。志愿者将获得18 65岁以下，讲英语，无CNS病史 紊乱没有受试者因饮酒而被排除 因为PCE和酒精之间相互作用是研究兴趣。的 咖啡因和酒精的直接影响将得到控制。评价 每个商店内的安全效应，每个暴露区域的志愿者 会得到考验年龄和教育的潜在混杂效应将是 通过分层和多元回归的方法控制。到 评估急性中枢神经系统影响，高暴露组和非暴露组将 在暴露前和暴露后进行了测试。估计潜在工作的程度 在测试健康工人时的选择偏差，42名以前接触过的工人 还将从10年前的就业名册中进行跟踪和评估 症状和行为的影响。 完成拟议的研究将记录一个可能的连续体， 在其中一个受试者中暴露于PCE后的亚临床至临床CNS效应 少数工业人口经常接触到超过40 ppm的高浓度。 慢性CNS效应的患病率描述为0 - 100 ppm，以及不良症状、行为和 在拟定的OSHA PEL为25 ppm时，生理效应是已知的。

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.