COMPARATIVE COMPUTATIONAL MODELING OF AIRFLOWS AND VAPOR DOSIMETY IN THE RESPIRATORY TRACTS OF RAT, MONKEY, AND HUMAN

Journal Article · Sun Jul 01 04:00:00 EDT 2012 · Toxicological Sciences

DOI:https://doi.org/10.1093/toxsci/kfs168· OSTI ID:1051179

Corley, Richard A; Kabilan, Senthil; Kuprat, Andrew P; Carson, James P; Minard, Kevin R; Jacob, Rick E; Timchalk, Charles; Glenny, Robb W; Pipavath, Sudhaker; Cox, Timothy C; Wallis, Chris; Larson, Richard; Fanucchi, M; Postlewait, Ed; Einstein, Daniel R

Coupling computational fluid dynamics (CFD) with physiologically based pharmacokinetic (PBPK) models is 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. Historically, these models were limited to discrete regions of the respiratory system. CFD/PBPK models have now been developed for the rat, monkey, and human that encompass airways from the nose or mouth to the lung. A PBPK model previously developed to describe acrolein uptake in nasal tissues was adapted to the extended airway models as an example application. Model parameters for each anatomic region were obtained from the literature, measured directly, or estimated from published data. Airflow and site-specific acrolein uptake patterns were determined under steadystate inhalation conditions to provide direct comparisons with prior data and nasalonly simulations. Results confirmed that regional uptake was dependent upon airflow rates and acrolein concentrations with nasal extraction efficiencies predicted to be greatest in the rat, followed by the monkey, then the human. For human oral-breathing simulations, acrolein uptake rates in oropharyngeal and laryngeal tissues were comparable to nasal tissues following nasal breathing under the same exposure conditions. For both breathing modes, higher uptake rates were predicted for lower tracheo-bronchial tissues of humans than either the rat or monkey. These extended airway models provide a unique foundation for comparing dosimetry across a significantly more extensive range of conducting airways in the rat, monkey, and human than prior CFD models.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1051179
• Report Number(s): PNNL-SA-83274; 25691; 400412000
• Journal Information: Toxicological Sciences, Journal Name: Toxicological Sciences Journal Issue: 2 Vol. 128; ISSN 1096-6080; ISSN TOSCF2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ACROLEIN
ANATOMY
Biotransformation and Toxicokinetics
respiratory
COMPUTERIZED SIMULATION
DOSIMETRY
Environmental Molecular Sciences Laboratory
FLUID MECHANICS
INHALATION
PHYSIOLOGY
RESPIRATION
RESPIRATORY SYSTEM
SIMULATION
physiologically-based pharmacokinetics
respiratory toxicology
biological modeling
risk assessment