Effects of the respiratory tract on inhaled materials

Inhalation exposure is often compared to intravenous or oral routes of administration with regard to the biological fate of inhaled materials. Such comparisons, however, overlook the contribution of respiratory tract enzymes to the metabolic fate and toxicity of inhaled materials. The effect of respiratory tract metabolism on the toxicity of inhaled materials is thought to be substantial for many compounds for the following reasons. (1) High concentrations of xenobiotic metabolizing enzymes occur in the nose and substantial concentrations occur in the lung. (2) The respiratory tract tissues are the first exposed to inhaled materials and are exposed to the highest concentrations (barring tissue specific uptake). (3) The products of respiratory tract metabolism may have different toxicities from those of hepatic metabolism. (4) Tissues at risk to toxic metabolites formed in the respiratory tract are different from those formed in the liver. These four reasons for concluding that respiratory tract metabolism may influence the toxicity of inhaled materials are backed by a solid body of expanding experimental data. Therefore, a complete assessment of the fate of inhaled materials should include assessment of potential contributions of respiratory tract metabolism.