Assessment of transient inhalation exposure using in silico human model integrated with PBPK-CFD hybrid analysis

This study presents a numerical assessment of transient tissue dosimetry in respiratory tracts using an in silico human 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.