Empirical modeling of particle deposition in the alveolar region of the lungs: a basis for interspecies extrapolation.

Different species exposed to the same particle atmosphere may not receive identical initial doses in comparable respiratory tract regions, and the selection of a certain species for toxicologic evaluation of inhaled particles may, thus, influence the estimated human lung, or systemic, dose, as well as its relationship to potential adverse health effects. Estimating regional particle deposition patterns is important for establishing the comparability of animal models, for understanding interspecies differences in the expression of chemical toxicities, and, ultimately, for the human risk assessment process. A method is described which offers a strategy for summarizing published data on regional deposition of particles of different diameters and calculating a deposited fraction for a particular particle size distribution. This involved the construction of nomograms to allow estimation of alveolar deposition fractions in three species, namely the human, monkey, and rat. A regression model was then developed to permit the calculation of more exact deposition fractions. Although this paper describes the procedure for one region of the lungs, the same technique can be applied to other regions of the respiratory tract or to the total system for which deposition data are available. While this technique may facilitate the interpretation of available experimental results and their application to human health risk assessment, appropriate caution should be exercised in applying the developed nomograms given limitations of the deposition database upon which it is based.