経気道曝露リスク評価のためのPBPK- CFDモデルの統合

 The effects of air pollution found in indoors and prevention of exposure to hazardous compounds are an important issue in the interest of public health. The overarching objective of this research series (Part 1, 2 and 3) were to develop a comprehensive and universal computer-simulated person (CSP) that integrated two types of physiological models; (i) thermo-regulation model for controlling skin surface temperature and (ii) respiratory tract model coupled with pharmacokinetics, for indoor environmental quality assessment. The previous reported papers (Part 1 and Part 2) of this research series had discussed the detail coupling procedure of virtual manikin and numerical respiratory tract by way of convective heat and moisture transfer analyses and also the improvement of thermo-regulation model by detail numerical analysis in numerical respiratory tract.<br> Especially, this paper (Part 3) treats the development of integrated numerical simulation method of Physiologically Based Pharmaco- Kinetic (PBPK) model and Computational Fluid Dynamics (CFD) for estimating respiratory tract tissue dosimetry. The PBPK-CFD model was incorporated into numerical airway model that integrated into CSP. Here, inhalation exposure and its health impact were analyzed by using PBPK-CFD-CSP model under the indoor environmental condition with formaldehyde constantly emitted from building materials.<br> In this study, in order to demonstrate the performance of PBPK-CFD-CSP method, simple room model with a CSP standing at the center of the floor was set as analytical domain. It was assumed that formaldehyde was emitted from the floor material with constant flux. In order to discuss the impact of inhalation exposure, a numerical analysis was performed under a steady-state condition and hence a constant breathing airflow rate of 7.5 L/min was applied. In the room model, supply inlet opening, which was located at the lower part of front wall of the CSP, was set as the inflow boundary condition at U_in = 0.1 m/s, and the exhaust outlet was located at the upper part of back wall of the CSP with zero gradient condition.<br> In this room model, non-uniform flow, temperature and formaldehyde concentration distributions were confirmed. In the viewpoint of inhalation exposure, it was revealed that over 95% of the formaldehyde adsorption flux was concentrated in the nasal cavity and nasopharynx. Inhalation concentration of formaldehyde at nostril was about 62.7 μg/m³ in this analytical condition. The adsorption flux and air (lumen of respiratory tract)- tissue (epithelium) interface concentration of formaldehyde on the nasal cavity and nasopharynx were transferred as the boundary conditions of PBPK analysis.<br> The PBPK model could predict formaldehyde disposition/ pharmacokinetic in the human body in detail. Using this method, formaldehyde concentration distributions in tissue could be precisely analyzed. As a result of the tissue dose of inhaled formaldehyde and its distributions based on PBPK analysis, the order of the rate of saturable metabolic clearance, 1st order reaction and blood perfusion inside a tissue and so on, could be quantitatively discussed.