COMPUTER-SIMULATION OF INSPIRATORY AIR-FLOW IN ALL REGIONS OF THE F344 RAT NASAL PASSAGES

Data from laboratory animal experiments are often used in setting guid elines for safe levels of human exposure to inhaled materials, The F34 4 rat has been used extensively in laboratory experiments to determine effects of exposure to inhaled materials in the nasal passages. Many inhaled materials induce toxic responses in the olfactory (posterior) region of the rat nasal passages. The location of major airflow routes has been proposed as playing a dominant role in determining some olfa ctory lesion location patterns. Since nasal airflow patterns differ si gnificantly among species, methods are needed to assess conditions und er which these differences may significantly affect extrapolation of t he effects of local dose in animals to potential disease outcome in hu mans, A computational fluid dynamics model of airflow and inhaled gas uptake has been used to predict dose to airway walls in the anterior F 344 rat nasal passages (Kimbell et al., Toxicol. Appl. Pharmacol., 199 3; 121, 253-263), To determine the role of nasal airflow patterns in a ffecting olfactory lesion distribution, this model was extended to inc lude the olfactory region. Serial-step histological sections of the na sal passages of a F344 rat were used to construct the computer model. Simulations of inspiratory airflow throughout the rat nasal passages w ere consistent with previously reported experimental data, Four of the five major simulated flow streams present in the anterior nose (dorsa l lateral, middle, ventral lateral, and ventral medial streams) flowed together to exit ventrally at the nasopharyngeal duct, bypassing the ethmoid recesses. The remaining dorsal medial stream split to flow bot h medially and laterally through the olfactory-epithelium-lined ethmoi d recesses in a Z-shaped pattern when viewed sagitally. Simulated flow in the ethmoid recesses was more than an order of magnitude slower th an flow in the anterior and ventral parts of the nasal passages. Somew hat higher volumes of flow were predicted in the dorsal medial stream when the nasal vestibule was reshaped to be upturned, and more flow wa s allocated to the dorsal medial stream with increased inspiratory air flow rate, suggesting that rats may be able to allocate more airflow t o this stream by both modifying the shape of the nasal vestibule and i ncreasing inhaled air velocity during sniffing, The present study prov ides the first description of flow in the complex olfactory region of the nose of the F344 rat, This model will be used to evaluate the role of airflow patterns in determining the distribution of xenobiotically induced olfactory mucosal lesions. This information, combined with mo dels of disposition in the airway lining, will provide comprehensive d osimetry models for extrapolating animal response data to humans. (C) 1997 Academic Press.