Use of computational fluid dynamics models for dosimetry of inhaled gases in the nasal passages.
Computational fluid dynamics (CFD) models of the nasal passages of a rat, monkey, and human are being used (1) to determine important factors affecting nasal uptake, (2) to make interspecies dosimetric comparisons, (3) to provide detailed anatomical information for the rat, monkey, and human nasal passages, and (4) to provide estimates of regional air-phase mass transport coefficients (a measure of the resistance to gas transport from inhaled air to airway walls) in the nasal passages of all three species. For many inhaled materials, lesion location in the nose follows patterns that are both site and species specific. For reactive, water-soluble (Category 1) gases, regional uptake can be a major factor in determining lesion location. Since direct measurement of airflow and uptake is experimentally difficult, CFD models are used here to predict uptake patterns quantitatively in three-dimensional reconstructions of the F344 rat, rhesus monkey, and human nasal passages. In formaldehyde uptake simulations, absorption processes were assumed to be as rapid as possible, and regional flux (transport rate) of inhaled formaldehyde to airway walls was calculated for rats, primates, and humans. For uptake of gases like vinyl acetate and acrylic acid vapors, physiologically based pharmacokinetic uptake models incorporating anatomical and physical information from the CFD models were developed to estimate nasal tissue dose in animals and humans. The use of biologically based models in risk assessment makes sources of uncertainty explicit and, in doing so, allows quantification of uncertainty through sensitivity analyses. Limited resources can then be focused on reduction of important sources of uncertainty to make risk estimates more accurate.
Kimbell
J S
JS
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA. kimbell@ciit.org
Subramaniam
R P
RP
D000818:Animals; D005557:Formaldehyde; D006801:Humans; D019570:Inhalation Exposure / Q000706:statistics & numerical data*; D008953:Models, Anatomic; D009296:Nasal Cavity / Q000033:anatomy & histology* / Q000502:physiology
D005557:Formaldehyde