CENTRAL NERVOUS SYSTEM EFFECTS OF PCE EXPOSURE IN HUMANS

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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.