One tenet of the science of toxicology is that of dose-response, viz., the magnitude of the response is dependent upon the dose of toxicant. Regional deposition is important in determining the local dose and, therefore, the response of the respiratory tract to inhaled toxic gases. Previous studies in this laboratory have shown that nasal deposition of ethanol and acetone vapors in the Sprague-Dawley rat can be described by pulmonary ventilation-perfusion models suggesting that the nasal epithelial membrane is sufficiently thin to allow equilibration of gas molecules between the inspired air and the nasal capillary blood. The proposed experiments are aimed at determining if pulmonary ventilation-perfusion models can be successfully applied to describe the nasal deposition process in a variety of species, and at providing detailed information on interspecies variability in the nasal gas deposition process. Towards these ends, acetone and ethanol deposition efficiencies will be measured in the surgically isolated nasal cavity of the anesthetized mouse, hamster, Fischer 344 rat, guinea pig and rabbit at a variety of physiologic inspiratory rates, and the data obtained will be analyzed by analogy to pulmonary ventilation-perfusion models. Goals of inhalation toxicologic research include prediction of toxic risk to man on the basis of animal studies, and elucidation of mechanisms of toxic injury. Since regional deposition is of primary importance in determining the dose of inhaled toxicant received by various regions of the respiratory tract, knowledge of interspecies variability in regional gas deposition would be extremely useful in selecting appropriate species for inhalation research and in interpreting and comparing the toxic responses of various species to inhaled gaseous toxicants. The proposed research, by providing detailed information on species-specific variability in the nasal gas deposition process, will, in the long-term, advance the science of inhalation toxicology. In addition, these experiments may elucidate a general mammalian phenomenon, viz., the exchange and equilibration of inert gas molecules across the nasal as well as the alveolar epithelial membranes.
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