Influence of exposure concentration or dose on the distribution of particulate material in rat and human lungs

Differences among species in the anatomic sites of particle retention could influence responses to inhaled particles. In this study, we used morphomet ric techniques to examine the influence of exposure concentration on partic le retention in histologic sections from rats and humans. The rats had been exposed for 24 months to diesel exhaust at 0.35, 3.5, or 7.0 mg soot/m(3). The human subjects were nonsmokers who did not work as miners, nonsmoking coal miners who worked under the current standard of less than or equal to2 mg dust/m(3) for 10-20 years (mean = 14 years), and nonsmoking coal miners who worked under the former standard of <10 mg dust/m(3) for 33-50 years ( mean = 40 years). The distribution of retained particles within the lung co mpartments was markedly different between species. In ail three groups of r ats, 82-85% of the retained particulate material was located in the alveola r and alveolar duct lumens, primarily in macrophages. In humans, 57, 68, an d 91% of the retained particulate material was Located in the interstitium of the lung in the nonminers, coal miners under the current standard, and c oal miners under the former standard, respectively. These results show that chronically inhaled diesel soot is retained predominately in the airspaces of rats over it wide range of exposures, whereas in humans, chronically in haled particulate material is retained primarily in the interstitium. In hu mans, the percentage of particles in the interstitium is increased with inc reased dose (exposure concentration years of exposure, and/or lung burden). This difference in distribution may bring different lung cells into contac t with the retained particles or particle-containing macrophages in rats an d humans and may account for differences in species response to inhaled par ticles.