An Empirical Dosimetry Model of Aerodynamic Particle Deposition in the Rat Respiratory Tract

Abstract

Models of airborne particle behavior in both the rodent and the human lung are needed to evaluate health effects following inhalation exposures for human health risk assessment as well as for therapeutic applications. We describe an empirical dosimetry model that can be used to predict fractional deposition of particles in the aerodynamic size range (i.e., diameter >0.5 μm) in the extrathoracic (ET), tracheobronchial (TB), and alveolar (A) regions of the rat lung. Independent equations for deposition efficiency of monodisperse particles in each of the three regions were selected after evaluating three unique functions as well as different parameterizations of independent variables consistent with the mechanisms of particle deposition in each region. For all of the functions fit to the deposition efficiency data, the asymptotic R² exceeded 0.95. Based on comparisons of the root mean square error (MSE) from the different deposition efficiency equations, as well as of other statistical tests, the logistic function was generally found to describe the data well. Limitations in the measurements that could be made on animals during an exposure, relative to those that have been made in the human studies, decrease the ability of an animal empirical model to incorporate biological factors known to improve prediction by the human empirical models. Allometric scaling of some of these parameters (such as tidal volume and the ET region airway volume) suggested that use of more biologically realistic explanatory variables in the deposition efficiency equations might not change predicted regional fractional deposition substantially in the empirical rat model. Additional animal experiments are necessary to address the issue of model specification more rigorously. The deposition efficiency equations were developed using experimental measurements of deposition of monodisperse particles in rats. To predict fractional deposition, predicted regional deposition efficiencies (calculated from the deposition efficiency equations) or their complements are multiplied together as appropriate. This predicted fractional deposition is the fractional deposition for particles that are inhaled. Because some particles have a low probability of entering the respiratory tract and this probability differs between species, it is important to adjust predicted fractional deposition for inhalability. Model results are presented to illustrate the effect of inhalability on predicted fractional deposition.