Assessment of transient inhalation exposure using in silico human model integrated with PBPK-CFD hybrid analysis
Assessment of transient inhalation exposure using in silico human model integrated with PBPK-CFD hybrid analysis
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DOI：
10.1016/j.scs.2018.04.023
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发表时间：
2018-07
影响因子：
11.7
通讯作者：
S. Yoo;Kazuhide Ito
中科院分区：
文献类型：
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作者：
S. Yoo;Kazuhide Ito
本研究使用计算机模拟人模型对呼吸道中的瞬时组织剂量测定进行了数值评估，即，计算机模拟人（CSP）在这项研究中，我们采用了一种新开发的CSP，它集成了实际形状的人体几何形状与虚拟气道再现现实的人体呼吸道。此外，将基于生理学的药代动力学（PBPK）-计算流体动力学（CFD）混合分析整合到基于CSP的数值模拟中，以使用非稳态呼吸循环模型估计吸入暴露和呼吸组织剂量学。为探讨PBPK-CFD-CSP混合分析在室内环境吸入暴露评价中的适用性，对瞬态条件下的吸入暴露进行了定量分析，并进行了模型验证。因此，室内空间中的非均匀和瞬时污染物浓度，以及时间依赖的吸入甲醛浓度，包括吸附分布，即，精确分析了呼吸道中的非均匀组织剂量学。超过50%的吸入甲醛被证实吸附在鼻腔的上皮+粘液层上，并在饱和代谢的影响下在该层反应/分解。根据呼吸道内复杂的流动模式，在咽部和喉部也证实了一个离散的局部“热点”。
This study presents a numerical assessment of transient tissue dosimetry in respiratory tracts using anin silicohuman model,i.e., computer simulated person (CSP). In this study, we employed a newly developed CSP, which integrated the actual shape of the human body geometry with a virtual airway reproduced realistic human respiratory tract. In addition, physiologically-based pharmacokinetic (PBPK)-computational fluid dynamics (CFD) hybrid analysis was integrated into the CSP-based numerical simulation to estimate inhalation exposure and respiratory tissue dosimetry with the unsteady breathing cycle model. In order to discuss the applicability of PBPK-CFD-CSP hybrid analysis for inhalation exposure assessment in indoor environments, inhalation exposure under transient conditions was quantitatively analyzed with a model validation. As a result, heterogeneous and transient contaminant concentration in indoor spaces, and time-dependent inhaled formaldehyde concentration including adsorption distributions,i.e., heterogeneous tissue dosimetry in the respiratory tract were precisely analyzed. Over the 50% of inhaled formaldehyde was confirmed to be adsorbed on the epithelium + mucus layer of the nasal cavity and reacted/decomposed at this layer under the influence of the saturable metabolism. A discrete and local “hot spot” was also confirmed at the pharynx and larynx in accordance with the complicated flow pattern in the respiratory tract.