Integration of Life-Stage Physiologically Based Pharmacokinetic Models with Adverse Outcome Pathways and Environmental Exposure Models to Screen for Environmental Hazards

In this study, the framework was applied to estimate MOEs for chemicals that can potentially cause developmental toxicity following a putative AOP for fetal vasculogenesis/angiogenesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe chemical disposition during pregnancy, fetal, neonatal, and infant to adulthood stages. Using this life-stage PBPK model, maternal exposures were estimated that would yield fetal blood levels equivalent to the chemical concentration that altered in vitro activity of selected HTS assays related to the most sensitive vasculogenesis/angiogenesis putative AOP. The resulting maternal exposure estimates were then compared with potential exposure levels using literature data or exposure models to derive AOP-based MOEs.
Source: Toxicological Sciences - Category: Toxicology Authors: Tags: Integration of PBPK and AOPs for Environmental Hazard Assessment Source Type: research