RETENTION MODELING OF DIESEL EXHAUST PARTICLES IN RATS AND HUMANS

The objective of this study was to predict the lung burden of diesel exhaust particles (DEPs) from automobile emissions in rats and humans by means of a mathematical model. We previously developed a model to predict the deposition of DEPs in the lungs of these species. In this study, the clearance and retention of deposited DEPs in the lung are examined. A diesel particle is composed of a carbonaceous core (soot) and the adsorbed organics. These materials can be removed from the lung after deposition by two mechanisms: (a) mechanical clearance, provided by mucociliary transport in the ciliated airways as well as macrophage phagocytosis and migration in the non-ciliated airways, and (b) clearance by dissolution. We used a compartmental model consisting of four anatomical compartments to study the clearance of DEPs from the lung: nasopharyngeal, tracheobronchial, alveolar, and the lung-associated lymph node compartments. We also assumed a particle model made up of material components according to the characteristics of clearance: (1) a carbonaceous core of about 80 percent of particle mass, (2) slowly cleared organics of about 10 percent of particle mass, and (3) fast cleared organics accounting for the remaining 10 percent of particle mass. The kinetic equations of the retention model were first developed for Fischer 344 rats. The transport rates of each material component of DEPs (soot, slowly cleared organics, fast cleared organics) were derived using available experimental data and several mathematical approximations. The lung burden results calculated from the model showed that while the organics were cleared at nearly constant rates, the alveolar clearance rate of diesel soot decreased with increasing lung burden. This is consistent with existing experimental observations. At low lung burdens, the alveolar clearance rate of diesel soot was a constant, equal to the normal clearance rate controlled by macrophage migration to the mucociliary escalator, whereas at high lung burdens, the clearance rate was determined principally by transport to the lymphatic system. The retention model of DEPs for rats was extrapolated to humans of different age groups from birth to adulthood. To derive the transport rates for the human model, the mechanical clearance from the alveolar region of the lung was assumed to be dependent on the specific particulate burden on the alveolar surface. The reduction in the mechanical clearance in adult humans due to high concentration exposure was found to be much less than that observed in rats. The reduction in children was greater than that in adults. For clearance by dissolution, the transport rates were assumed to be the same for humans and rats. We combined the retention model of DEPs and the deposition model for these particles to compute the accumulated mass of diesel soot and the associated organics in various compartments of the human lung under different exposure conditions. It was found that the lung burdens of both diesel soot and the associated organics were much higher in humans than in rats for the same period of exposure because of the higher particle intake and slower clearance rate in humans. The reduction in clearance caused by excessive lung burdens would not occur in human if the exposure concentration was kept below 0.05 mg/m3. Also, it was found that for the same exposure, the lung burden per unit lung weight was higher in children and reached a maximum at about 5 years of age. These results are of use in health risk assessment due to DEP exposure.