Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlus™ physiologically based pharmacokinetic modelling

Publication: SAR QSAR Environ Res
Software: GastroPlus®


A physiologically based pharmacokinetic (PBPK) model for the important chemical phenoxyethanol (PhE) and its metabolite phenoxyacetic acid (PhAA) was built via GastroPlusTM software (version 9.0) using currently available analytically measured plasma and urinary time-courses of both PhE and its metabolite PhAA. This model was validated and used to predict tissue and urine concentrations of PhE and its metabolite PhAA in rats and humans after oral and dermal exposures. The prediction results showed that most predicted tissue concentrations of PhE or PhAA were lower than the experimental tissue concentrations based on total radioactivity. The predicted cumulative excretion of PhAA in both rats and humans fits very well with most experimental data. With this GastroPlusTM-based model, the margins of exposure (MOE) of PhE and PhAA were also calculated as 194 and 73.7, respectively. The predicted MOE of PhE is two-fold higher than the previous PBPK model built using total radioactivity-based tissue time courses, and the predicted MOE of PhAA was comparable to the previous PBPK model. These data indicate that for chemicals like PhE, GastroPlusTM can integrate multiple data sets into PBPK models to predict PK parameters for parent and metabolites in both rats and humans following intravenous, dermal, or oral exposures.

By F. Zhang, M.J. LeBaron, M.S. Marty