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Differences among species in the anatomic sites of particle retention could influence responses to inhaled particles. In this study, we used morphometric techniques to examine the influence of exposure concentration on particle 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 2 mg dust/m(3) for 10-20 years (mean = 14 years), and nonsmoking coal miners who worked under the former standard of &lt; 10 mg dust/m(3) for 33-50 years (mean = 40 years). The distribution of retained particles within the lung compartments was markedly different between species. In all three groups of rats, 82-85% of the retained particulate material was located in the alveolar and alveolar duct lumens, primarily in macrophages. In humans, 57, 68, and 91% of the retained particulate material was located in the interstitium of the lung in the non-miners, coal miners under the current standard, and coal miners under the former standard, respectively. These results show that chronically inhaled diesel soot is retained predominantly in the airspaces of rats over a wide range of exposures, whereas in humans, chronically inhaled particulate material is retained primarily in the interstitium. In humans, the percentage of particles in the interstitium is increased with increased dose (exposure concentration, years of exposure, and/or lung burden). This difference in distribution may bring different lung cells into contact with the retained particles or particle-containing macrophages in rats and humans and may account for differences in species response to inhaled particles.

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