Prediction of the exposure profile of bisphenol A in Chinese population by physiologically-based pharmacokinetics modeling

Bisphenol A (BPA) has emerged as a typical contaminant which can induce various adverse effects on human health and environment. BPA exposure and the corresponding human responses vary across different regions and populations. China is one of the largest producers and consumers of BPA, but the exposure profile of BPA in Chinese population is poorly understood. Physiologically-based pharmacokinetic (PBPK) models are emerging as useful tools to predict the internal exposure profiles of chemicals. Herein, the present study was aimed to predict the exposure profile of BPA in Chinese population by PBPK modeling using external BPA exposure data. A PBPK model specific for oral BPA exposure in Chinese population was established using interspecies and route-to-route extrapolations using pharmacokinetic data from intravenous BPA exposure studies in monkeys. This model was refined and validated using the data concerning BPA physicochemical properties and pharmacokinetic (absorption, distribution, metabolism, and excretion) data from existing literatures. Afterward, this model was applied to simulate the internal exposure profile of BPA in Chinese population by integrating external exposure data from the Fifth China Total Diet Survey with physiological parameters specific to Chinese population. Parameter sensitivity and modeling uncertainty were analyzed. Based on the simulated BPA internal profile, human equivalent dose factors (HEDF) were calculated. Our results provide an important basis for assessment of the potential risk of BPA exposure in Chinese population and an essential reference for determination of the safe margin limits for BPA in China.