BIOMARKERS OF ENVIRONMENTAL BENZENE EXPOSURE

Environmental exposures to benzene result in increases in body burden that are reflected in Various biomarkers of exposure, including benzen e in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicate s that these biomarkers can be used to distinguish populations with di fferent levels of exposure (such as smokers from nonsmokers and occupa tionally exposed from environmentally exposed populations) and to dete rmine differences in metabolism. Biomarkers in humans have shown that the percentage of benzene metabolized by the ring-opening pathway is g reater at environmental exposures than that at higher occupational exp osures, a trend similar to that found in animal studies. This suggests that the dose-response curve is nonlinear; that potential different m etabolic mechanisms exist at high and low doses; and that the validity of a linear extrapolation of adverse effects measured at high doses t o a population exposed to lower, environmental levels of benzene is un certain. Time-series measurements of the biomarker, exhaled breath. we re used to evaluate a physiologically based pharmacokinetic (PBPK) mod el. Biases were identified between the PBPK model predictions and expe rimental data that were adequately described using an empirical compar tmental model. it is suggested that a mapping of the PBPK model to a c ompartmental model can be done to optimize the parameters in the PBPK model to provide a future framework for developing a population physio logically based pharmacokinetic model.