Pulmonary Retention of Inhaled Submicron Particles in Rats: Diesel Exhaust Exposures and Lung Retention Model

Abstract

Inhalation exposures to diluted diesel exhaust were conducted in male F344 rats for the last five years to enable a better understanding of lung clearance of inhaled diesel particles (DP). We observed that as the DP burden in the lungs increased, lung clearance decreased and the extent of particle-laden macrophage aggregation in the alveoli increased. A new compartmental model of particle retention in the lungs was developed by treating the macrophage aggregates as a particle sequestering compartment. Features of the model are non-linear compartmental clearance of particulate and a mass-dependent transition from elimination to sequestration of particulate in the lungs. A new experimental exposure for 12 weeks to 6 mg DP/m³ was conducted to collect data on the transition from elimination to sequestration of particles in the lungs and regional lymph nodes. This report describes a new multi-compartmental model which closely simulates the data for both lung and lymph node particle burdens during the exposure and post-exposure periods.