Predicted lung burdens of diesel exhaust particles in rats and humans

The objective of this study was to determine the lung burden of diesel exhaust particles (DEPs) in rats and humans using a mathematical model. A mathematical model which describes the clearance and retention of deposited DEPs in the lung was studied.; A diesel particle is composed of a carbonaceous core (soot) and the adsorbed organics. Both materials can be removed from the lung after deposition by two mechanisms: (a) mechanical clearance and (b) clearance by dissolution. We used a compartmental model consisting of six anatomical compartments to study the clearance of DEPs from the lung. We also assumed a particle model made up of material components according to the characteristics of clearance: (1) a carbonaceous core, (2) organics strongly bound to the core, and (3) organics weakly bound to the core.; A retention model of DEPs for rats was first developed. The transport rates of each material component of DEPs were obtained from the best statistical fits of available experimental data. The results showed that while the organics were cleared at constant rates, the alveolar clearance rate of diesel soot decreased with increasing lung burden.; The retention model of DEPs for rats was extrapolated to humans of different age groups. Mechanical transport rate of diesel soot was extrapolated assuming that the variation of the dimensionless alveolar clearance rate with the particulate burden per unit area of pulmonary surface was species independent. For the organic portions of DEPs, the transport rates were assumed to be the same for humans and rats.; We combined the retention model of DEPs and the deposition model that we previously developed for DEPs to compute the lung burdens of diesel soot and the associated organics for humans under different exposure conditions.; Based on the results of our retention model and the lung tumor incidence data of rats associated with DEPs exposure, we determined several dose-response relationships. These relationships were extrapolated to humans to assess the relative lung cancer risks associated with DEPs exposure.