Benzene metabolism by the isolated perfused lung

Benzene is an occupational hazard and environmental toxicant whose toxic effects are dependent on its metabolism by cytochrome P-450. Most physiologically based pharmacokinetic models assume that benzene is metabolized only in the liver. They may not be completely accurate in predicting metabolism, especially following inhalation exposure, if metabolism by the lung is important. In the current study, the metabolizing capability of the lung was examined in an in vivo simulation using the isolated perfused lung. Lungs from the rabbit, rat, and mouse were used to mimic benzene metabolism following exposure via the pulmonary vasculature. With the isolated perfused mouse lung, three concentrations (55 microM, 120 microM, and 200 microM) were used to evaluate concentration dependence. To evaluate the ability of the lung to metabolize inhaled benzene, the isolated perfused mouse lung was exposed to benzene (approximately 175 ppm) via the trachea. Benzene was metabolized in all species, with phenol being the major metabolite. Phenylsulfate was also detected in perfusate from rabbits and mice but at much lower levels. Benzene metabolism was concentration dependent in mice. The ability of the lung to metabolize benzene during inhalation exposure was demonstrated in the isolated perfused mouse lung. These results demonstrate that the lung can metabolize benzene in an in vivo simulation when exposed via the pulmonary vasculature or via inhalation.