Construction of a physiologically based pharmacokinetic model for some environmental phenols

Abstract

It is important to know the exposure levels of environmental phenolic compounds considering their exposure frequency and toxicity. Physiologically based pharmacokinetic (PBPK) model is one of the tools for predicting the daily intake value. Most of the PBPK models were developed for single chemical so several models are required to do exposure assessment for several chemicals. A simple PBPK model was developed for several environmental phenols (methyl paraben, ethyl paraben, propyl paraben, benzophenono-3, triclosan, bisphenol A, bisphenol S) that provides a description of kinetics of those chemicals in human. Since those phenolic compounds share similar chemical structure and pharmacokinetic characteristics, constructing a unified model for them would reduce the cost and time. Structure of the developed model consists of liver, skin, rest-of-the-body and blood compartments. Once the chemical comes into the liver compartment, metabolism happens and the metabolites excretes into feces or urine after moving to the blood compartment. The model parameters were optimized using data of published pharmacokinetic studies in humans. Then to confirm the validity, the model was applied to other human kinetic data not used in the model calibration except benzophenone-3. Model simulations were visually fitted well to the experimental data of most of the target chemicals except propyl paraben. It appears that the model under-predicted accumulated urinary amount of total propyl paraben. The results of this study is meaningful that the constructed model can be applied to various phenolic compounds with one model structure and it can be used to predict more elaborate intake values that can reflect the physiochemical characteristics of human body. In addition, the result of this study implicated that the model structure could explain pharmacokinetic behavior of various phenols so it could be considered that the extended application of the model to other phenols sharing similar pharmacokinetic properties.