A toxikinetic model for simulation of benzene metabolism

People exposed to benzene, an important industrial solvent and a common pollutant, can develop aplastic anemia and leukemia. The objectives of this study were to develop a physiological model for the metabolism of benzene, based on studies in laboratory animals, and to use this model to predict benzene metabolism in people to concentrations near the current permissible exposure limits. Model simulations predicted that for 8-h inhalation exposures to below 10 ppm, hydroquinone metabolites would predominate. Hydroquinone is associated with pathways leading to the formation of the putative toxic metabolite, benzoquinone. Lower levels of muconic acid, a marker for the putative toxic metabolite, muconaldehyde, were predicted. At concentrations above 10 ppm, detoxification metabolites such as the phenyl conjugates predominate. Predictions of benzene metabolism in humans based on our physiological model may have important implications for risk assessment. Because there may be preferential production of a putative toxic metabolite at low exposure concentrations, linear extrapolation of toxicity observed at high concentrations may underestimate risk at low exposure concentrations.