Kimbell J S, Subramaniam R P
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA.
Inhal Toxicol. 2001 May;13(5):325-34. doi: 10.1080/08958370151126185.
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.
大鼠、猴子和人类鼻腔通道的计算流体动力学（CFD）模型正被用于：（1）确定影响鼻腔摄取的重要因素；（2）进行种间剂量学比较；（3）提供大鼠、猴子和人类鼻腔通道的详细解剖信息；（4）估计这三种物种鼻腔通道中区域气相质量传输系数（衡量从吸入空气到气道壁的气体传输阻力的指标）。对于许多吸入物质，鼻腔内的损伤位置遵循特定部位和物种的模式。对于反应性、水溶性（1类）气体，区域摄取可能是决定损伤位置的主要因素。由于直接测量气流和摄取在实验上具有难度，因此这里使用CFD模型在F344大鼠、恒河猴和人类鼻腔通道的三维重建中定量预测摄取模式。在甲醛摄取模拟中，假定吸收过程尽可能迅速，并计算了大鼠、灵长类动物和人类吸入甲醛向气道壁的区域通量（传输速率）。对于醋酸乙烯酯和丙烯酸蒸汽等气体的摄取，开发了基于生理学的药代动力学摄取模型，该模型纳入了CFD模型的解剖学和物理信息，以估计动物和人类的鼻腔组织剂量。在风险评估中使用基于生物学的模型使不确定性来源明确，并且通过敏感性分析能够对不确定性进行量化。然后可以将有限的资源集中于减少重要的不确定性来源，以使风险估计更加准确。
