Can PBPK models be directly applied for internal exposure to indoor PAEs? A model analysis for vascular adsorption

Phthalates (PAEs) exhibit strong adsorption and lipophilicity, yet their adsorption on the blood vessel wall remains unattended. Current PBPK models neglect this adsorptive loss due to the presuming stable blood concentrations. During inhalation exposure, this effect may be overlooked, thereby overestimating systemic doses. This study aimed to quantify PAEs concentration loss in major blood vessels for PBPK model and evaluate the interception of the pulmonary vein tree on inhaled PAEs. A mass transfer model was developed to simulate vascular adsorption. This model was applied to simulate major vessels in the PBPK model. Furthermore, pulmonary vein trees interception on PAEs was simulated for young and elderly populations, while concentration losses of 15 common PAEs were quantified. The concentration loss of PAEs was minimal and nearly negligible in most vessels, except for capillaries where significant loss occurred. Among physiological parameters, vessel radius was identified as the key factor influencing concentration loss. Simulation of DEHP in the pulmonary vein tree further revealed that inner wall adsorption led to a concentration loss of 10.28% to 12.54%. A general trend was observed where PAEs with higher mass transfer coefficients exhibited greater concentration losses, although exceptions existed. Additionally, concentration loss was significantly higher in the elderly compared to young people. This study confirms the validity of blood transport assumptions in existing PBPK models for PAEs and highlights pulmonary vasculature’s role in intercepting inhaled PAEs. Findings provide theoretical support and key parameters for improving PBPK models and enabling more accurate PAEs internal exposure assessment during inhalation.