Retention modeling of diesel exhaust particles in rats and humans

The objective of this study was to predict the lung burden in rats and humans of diesel exhaust particles from automobile emissions by means of a mathematical model. We previously developed a model to predict the deposition of diesel exhaust particles in the lungs of these species. In this study, the clearance and retention of diesel exhaust particles deposited in the lung are examined. A diesel particle is composed of a carbonaceous core (soot) and adsorbed organics. These materials can be removed from the lung after deposition by two mechanisms: (1) mechanical clearance, provided by mucociliary transport in the ciliated airways as well as macrophage phagocytosis and migration in the nonciliated airways, and (2) clearance by dissolution. To study the clearance of diesel exhaust particles from the lung, we used a compartmental model consisting of four anatomical compartments: 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 diesel exhaust particles (soot, slowly cleared organics, and fast-cleared organics) were derived using available experimental data and several mathematical approximations. The lung burden results calculated from the model showed that although 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 diesel exhaust particles 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 caused by exposure to high concentrations of diesel exhaust was found to be much less than that observed in rats. The reduction in children was greater than that in adults.(ABSTRACT TRUNCATED AT 400 WORDS)