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

ABSTRACT: A computational framework was developed to assist in screening and prioritizing chemicals based on their dosimetry, toxicity, and potential exposures. The overall strategy started with contextualizing chemical activity observed in high-throughput toxicity screening (HTS) by mapping these assays to biological events described in Adverse Outcome Pathways (AOPs). Next, in vitro to in vivo (IVIVE) extrapolation was used to convert an in vitro dose to an external exposure level, which was compared with potential exposure levels to derive an AOP-based margins of exposure (MOE). 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 pharmacokin

SUBMITTER: El-Masri H 

PROVIDER: S-EPMC5009469 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature