Development of a physiologically based pharmacokinetic model for assessment of human exposure to bisphenol A

摘要: A previously developed physiologically based pharmacokinetic (PBPK) model for bisphenol (BPA) in adult rhesus monkeys was modified to characterize the pharmacokinetics of BPA and its phase II conjugates humans following oral ingestion. Coupled with vitro studies on metabolism liver small intestine, PBPK parameterized using data deuterated-BPA (d6-BPA) delivered cookies after overnight fasting. The availability serum concentration time course unconjugated d6-BPA offered direct empirical evidence calibration parameters. recalibrated human then evaluated against published BPA. hypothesis decreased uptake needed account reduced peak levels observed humans, where soup food provided prior ingestion, suggesting potential impact dosing vehicles and/or fasting disposition. With incorporation Monte Carlo analysis, used address inter-individual variability internal dose metrics U.S. general population. Model-predicted were range pM, 95% falling within an order magnitude. This provides a scientific basis assessing exposure that can serve minimize uncertainties incurred during extrapolations across doses species.