Incorporation of Nasal-Lining Mass-Transfer Resistance into Acfd Model for Prediction of Ozone Dosimetry in the Upper Respiratory Tract

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Abstract
Inhalation of ambient concentrations of ozone (a strong oxidant) has been reported to injure regions of the monkey and rat upper respiratory tract (URT) that contain little intraepithelial mucosubstances (regions lined by transitional epithelium) and to spare adjacent regions that contain abundant stored secretory products (regions lined by respiratory epithelium). It is therefore hypothesized that mucus provides a major resistance to ozone mass transport in the URT. As part of a larger project to predict health risks of inhaled gases, a previously developed, computational fluid dynamics (CFD) model of the Fischer 344 (F344) rat nasal passage was modified to describe transport of ozone. In this study, mass-transfer resistance in the nasal lining was incorporated into the CFD model for prediction of ozone dosimetry. Static mucus and tissue layers were considered. A boundary condition was developed that incorporates mass-transfer resistance in the nasal lining due to one-dimensional diffusion and first-order reaction in the mucus and tissue phases. Physicochemical parameters for ozone were obtained from the literature. Resistance to mass transfer in the submucosal region (blood phase) was neglected due to high tissue-phase reactivity (i.e., the concentration of inhaled chemical in blood was set to zero). To study the possibility that differences in the thickness and/or quality (variation in physico-chemical properties) of mucus coating the transitional and respiratory epithelium account for reported patterns of injury, a simulation was performed into which regional differences in mucus thickness were incorporated. Results suggest that mass-transfer resistance in the mucus phase is important for describing ozone dosimetry in the URT. In addition, mucus thickness may play a role in determining the pattern of ozone-induced nasal lesions.