Journal Article

Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human

Richard A. Corley, Senthil Kabilan, Andrew P. Kuprat, James P. Carson, Kevin R. Minard, Richard E. Jacob, Charles Timchalk, Robb Glenny, Sudhakar Pipavath, Timothy Cox, Christopher D. Wallis, Richard F. Larson, Michelle V. Fanucchi, Edward M. Postlethwait and Daniel R. Einstein

in Toxicological Sciences

Volume 128, issue 2, pages 500-516
Published in print August 2012 | ISSN: 1096-6080
Published online May 2012 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfs168
Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human

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Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17±7, 19±9, or 9±2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models.

Keywords: CFD; PBPK; respiratory airflows; respiratory dosimetry; acrolein.

Journal Article.  13629 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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