Kepler G M, Richardson R B, Morgan K T, Kimbell J S
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709-2137, USA.
Toxicol Appl Pharmacol. 1998 May;150(1):1-11. doi: 10.1006/taap.1997.8350.
There is increasing evidence that inspiratory airflow patterns play a major role in determining the location of nasal lesions induced in rats by reactive, water-soluble gases such as formaldehyde and chlorine. Characteristic lesion patterns have also been seen in inhalation toxicity studies conducted in rhesus monkeys, the nasal anatomy of which resembles that of humans. To examine the hypothesis that regions of high airflow-dependent uptake and lesions occur in similar nasal locations in the primate, airflow and gas uptake patterns were simulated in an anatomically accurate computer model of the right nasal airway of a rhesus monkey. The results of finite-element simulations of steady-state inspiratory nasal airflow for the full range of resting physiological flow rates are reported. Simulated airflow patterns agreed well with experimental observations, exhibiting secondary flows in the anterior nose and streamlined flow posteriorly. Simulated airflow results were used to predict gas transport to the nasal passage walls using formaldehyde as an example compound. Results from the uptake simulations were compared with published observations of formaldehyde-induced nasal lesions in rhesus monkeys and indicated a strong correspondence between airflow-dependent transport patterns and local lesion sites. This rhesus computer model will provide a means for confirming the extrapolation of toxicity data between species by extrapolating rat simulation results to monkeys and comparing these predictions with primate lesion data.
越来越多的证据表明，吸气气流模式在决定由甲醛和氯等反应性水溶性气体诱导的大鼠鼻腔病变位置方面起着主要作用。在恒河猴身上进行的吸入毒性研究中也观察到了特征性的病变模式，恒河猴的鼻腔解剖结构与人类相似。为了检验高气流依赖性摄取区域和病变在灵长类动物鼻腔相似位置出现的假设，在恒河猴右鼻气道的解剖学精确计算机模型中模拟了气流和气体摄取模式。报告了在整个静息生理流速范围内稳态吸气鼻腔气流的有限元模拟结果。模拟的气流模式与实验观察结果非常吻合，在前鼻孔处呈现二次流，在后鼻孔处呈现流线型流。以甲醛为例，利用模拟气流结果预测气体向鼻道壁的传输。摄取模拟结果与已发表的恒河猴甲醛诱导鼻腔病变观察结果进行了比较，结果表明气流依赖性传输模式与局部病变部位之间存在很强的对应关系。这个恒河猴计算机模型将为通过将大鼠模拟结果外推到猴子并将这些预测与灵长类动物病变数据进行比较来确认物种间毒性数据的外推提供一种方法。
