NEUROBEHAVIORAL PERFORMANCE INDICES AS BIOMARKERS OF PERCHLOROETHYLENE EXPOSURE

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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.