A core physiologically based toxicokinetic (PBTK) model for exposure assessment of multiple environmental phenols

Abstract

Environmental phenols are widely used in consumer products and are of increasing concern due to their potential endocrine-disrupting effects. Physiologically based toxicokinetic (PBTK) models offer a powerful tool for estimating human exposure by translating biomonitoring data into external intake values. However, conventional PBTK models are typically chemical-specific and resource-intensive. In this study, we developed a core human PBTK model capable of describing the absorption, distribution, metabolism, and excretion (ADME) of four groups of environmental phenols—parabens (MeP, EtP, PrP), bisphenols (BPA, BPS), triclosan (TCS), and benzophenone-3 (BP-3)—based on shared toxicokinetic characteristics.

The model was calibrated and validated using human volunteer data and applied to urinary biomonitoring data from 3787 Korean adults in the Korean National Environmental Health Survey (KoNEHS 2015–2017). Estimated daily intakes (EDIs) for MeP, EtP, PrP, and BPA were estimated via reverse dosimetry and compared with values derived from the conventional fractional urinary excretion (F_ue) method. Median EDIs derived from the PBTK model were 3.7, 4.8, 0.4, and 0.02 μg/kg-bw/day for MeP, EtP, PrP, and BPA, respectively, and showed good agreement with F_ue based estimates.

The core model successfully captured blood and urinary concentration profiles across multiple phenols, demonstrating its potential as a practical and scalable framework for exposure assessment. Furthermore, the model was used in a reverse dosimetry framework to estimate human exposure levels from urinary biomonitoring data. This approach can be particularly valuable when chemical-specific models are unavailable, offering an efficient alternative for interpreting biomonitoring data in environmental health risk assessment.