The proposed study is intended to investigate the linkages between exposure, absorbed dose, and cytogenetic response resulting from occupational exposures to styrene in the reinforced-plastics industry. A longitudinal study is envisioned where a cohort of 20 highly-exposed workers (and 10 controls) is followed over a period of one year. Ideally the cohort will consist of equal numbers of workers exposed either more or less continuously from day to day or in a highly intermittent fashion. Randomly-selected surveys during the period of the study will allow each worker's airborne exposures to be repeatedly measured as well as his/her blood styrene levels (as indicated by analysis of exhaled air), and levels of sister chromatid exchanges (SCEs) in peripheral lymphocytes. The goal will be to estimate the parameters of the distributions of exposures, absorbed dose, and cytogenetic response so that the sensitivity of the dose and response distributions can be investigated relative to that of exposure. This should provide insight concerning the relative importance of large transient exposures or large daily exposures and of the possible need for a STEL in regulating styrene exposures. It should also provide valuable insight into the stability of SCEs in humans exposed to genotoxic agents. A secondary part of the study will be to apply a pharmacokinetic model for styrene, derived under constant-exposure conditions, to the situation typical of occupational exposures where air levels vary considerably over time. The input of the model will be a lognormally-distributed, autocorrelated series of exposure concentrations while the output consists of the resulting concentrations of styrene in the central and peripheral compartments. A portion of the field study will gather exposure-dose data over short averaging times in order to validate the model. If it proves useful, the model will be used to estimate patterns of short-term exposures and blood styrene levels associated with the majority of the field measurements where only 4-8 hr TWAs could be measured.
