Fate of Inhaled Particles in the Lungs of Ferrets

BAHMAN ASGHARIAN, Michael Oldham, Owen Price, Applied Research Associates, Inc.

     Abstract Number: 620
     Working Group: Health-Related Aerosols

Abstract
Ferrets have been recommended as an animal model in inhalation toxicology due to the ease of handing, utility in vaccine research and similarities to humans’ tracheobronchial geometry. Currently, there is no widely available particle dosimetry model for the ferret, that can be used to estimate inhaled doses or used for interspecies extrapolation. While transport mechanisms and thus deposition models are similar among most mammals and rodents, lung geometries and physiologies are species-specific. We developed a simplified computational lung geometry for ferrets based on available measurements in the literature (Oldham et al., 1990; Laboratory Animal Science 2:186-191). To accurately reflect the structure, a double-path tree branching structure was used for the tracheobronchial tree where one pathway accounted for the conducting airways and the second for the alveolar airways if present (airway generation 5 and beyond). The major advantage of the new geometry was that it avoided artificial separation of conducting and alveolar regions based on airway generation number particularly for lung geometries with monopodial structures prevalent in rodents. The proposed geometrical structure can replace typical-path models, often used in the literature, to predict particle deposition more accurately in all species. Ferret-specific lung volumes and breathing parameters were used to predict particle deposition in the ferret using the Multiple-Path Particle Dosimetry model (MPPD, Applied Research Associates, Raleigh, N.C.). Model predictions showed that while regional deposition followed a similar pattern to that of typical-path models, deposition distribution as a function of airway generation number was significantly different. Deposition of micrometer-sized particles tended to deposit in proximal airway generations whereas nanoparticle deposition occurred in more distal airways. The developed ferret model provides a more realistic prediction of particle deposition distribution in the respiratory tract of ferrets and will be a useful tool for risk assessment applications.