Historically, the recognition of environmental neurotoxins has followed from investigations of heavily exposed persons in occupation, environmental disaster or experimental settings. However, most neurotoxin exposures experienced by human populations are of low intensities, and anticipated health effects are likely to be subtle. Consequently, there is a need to develop reliable biochemical markers of early exposure effects which can be applied in epidemiologic investigations. Currently, researchers from The University of Washington Department of Environmental Health are exploring the utility of some peripheral bioindicators of neurotoxicity in controlled animal experiments. The overall objective of this investigation is to apply experimentally developed biochemical markers for neurotoxicity and chemical detoxification potential to a human population exposed occupationally to a known and quantifiable neurotoxic agent, styrene.
The specific aims of this research are: 1) to compare levels of dopamine D2 receptors, monoamine oxidase type B and serotonin uptake in circulating platelets, leukocyte concentrations of reduced glutathione, and leukocyte activities of glutathione-S-transferase and epoxide hydrolase between two groups of workers. Exposed subjects will be workers exposed to styrene in the reinforced plastics industry and a comparison group will be workers, matched with respect to gender, age and race, from other industries with no known exposures to neurotoxins ; 2) to evaluate expose-response relationships between the biochemical parameters and exposure levels, as indicated by concentrations of the styrene metabolites, mandelic and phenylglyoxylic acids; 3) to relate the prevalence of symptoms suggestive of central nervous system toxicity with biochemical markers among exposed and non-exposed subjects; and, 4) to measure changes of biochemical markers over time. These objectives will be achieved using a repeat measures study design wherein exposure, biochemical and clinical symptom data are obtained at two points in time. It is anticipated that this research will generate valuable information on biological responses to a known, widely used industrial neurotoxin. Moreover, this approach of applying laboratory assays of early indicators of toxicity in human populations may serve as a model strategy from evaluating potentially toxic effects to the nervous system and other target organs from environmental chemical exposures.

National Institute of Health (NIH)
National Institute for Occupational Safety and Health (NIOSH)
Research Project (R01)
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Safety and Occupational Health Study Section (SOH)
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University of Washington
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Brodkin, C A; Moon, J D; Camp, J et al. (2001) Serum hepatic biochemical activity in two populations of workers exposed to styrene. Occup Environ Med 58:95-102
Omiecinski, C J; Aicher, L; Holubkov, R et al. (1993) Human peripheral lymphocytes as indicators of microsomal epoxide hydrolase activity in liver and lung. Pharmacogenetics 3:150-8
Checkoway, H; Costa, L G; Camp, J et al. (1992) Peripheral markers of neurochemical function among workers exposed to styrene. Br J Ind Med 49:560-5