DR. MARY AMDUR MEMORIAL LECTURE

The laboratory rat has frequently been used as a human surrogate in inhalation toxicology to assess potential health effects of inhaled particulate matter. Differences in initial particle deposition patterns in the human and rat lungs may be attributed primarily to their differences in airway morphology, that is, a relatively symmetric division scheme in the human lung as compared to a distinct asymmetric branching pattern in the rat lung, and to their differences in breathing parameters. To account for the experimentally observed variability and asymmetry of airway bifurcations in both lungs, our present computations of particle deposition patterns are based on previously developed stochastic morphometric lung models. Regional (i.e., tracheobronchial and pulmonary) and local (i.e., airway-by-airway) deposition patterns were calculated for a wide range of unit density particle sizes (1 nm to 10 mum) and flow rates for nasal breathing conditions. Different human physical activities were characterized by specified breathing parameters, while corresponding ventilation intensities in rat inhalation experiments were simulated by different CO2 exposure levels. Since this study focuses on the relative distribution of deposited particles among bronchial and pulmonary airways, deposition patterns were normalized to the number of particles entering the trachea. While there are noticeable quantitative differences between the corresponding deposition patterns in both lungs, their dependence on particle size and flow rate is qualitatively similar. Due to the intrasubject variability in airway morphology and related flow rates, deposition fractions are highly variable within a given generation. As a result of this, regional and total deposition also exhibit intrasubject variations. In general, intrasubject variability in the pulmonary region is larger than that in the bronchial airways, while the dispersion of the frequency distribution is even further enlarged for total deposition. At the airway generation level, frequency distributions of deposition probabilities within bronchial airway generation 4 and bronchiolar airway generation 12 in the human lung can be approximated by lognormal distributions. In contrast, two distinct deposition maxima can be observed in upper bronchial airways of the rat lung, reflecting deposition in major and minor daughter airways. These two modes, however, disappear upon penetration deeper into the lung and are no longer discernible in airway generation 12.