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 rece ive identical initial doses in comparable respiratory tract regions, a nd the selection of a certain species for toxicologic evaluation of in haled particles may, thus, influence the estimated human lung, or syst emic, dose, as well as its relationship to potential adverse health ef fects. Estimating regional particle deposition patterns is important f or 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 descr ibed which offers a strategy for summarizing published data on regiona l deposition of particles of different diameters and calculating a dep osited fraction for a particular particle size distribution. This invo lved the construction of nomograms to allow estimation of alveolar dep osition fractions in three species, namely the human, monkey, and rat. A regression model was then developed to permit the calculation of mo re exact deposition fractions. Although this paper describes the proce dure 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 whi ch deposition data are available. While this technique may facilitate the interpretation of available experimental results and their applica tion to human health risk assessment, appropriate caution should be ex ercised in applying the developed nomograms given limitations of the d eposition database upon which it is based. (C) 1995 Society of Toxicol ogy