You are here:
Species-specific predictive models of developmental toxicity using the ToxCast chemical library
Citation:
SIPES, N. S. Species-specific predictive models of developmental toxicity using the ToxCast chemical library. Presented at The Society of Toxicology (SOT) 51st Annual Meeting and ToxExpo 2012, Moscone Convention Center , San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
The in vitro HTS profiles for 700 additional ToxCast Phase II chemicals, including failed pharmaceuticals, alternative plasticizers, and food additives are being used to validate and update the initial predictive models of developmental toxicity. These models have the potential to prioritize chemicals for further targeted toxicity testing and risk assessment, generate hypotheses about mechanistic pathways leading to adverse developmental outcomes, and reduce cost and increase throughput of chemical testing.
Description:
EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive models that correlate with observed in vivo toxicity. In vitro profiling methods are based on ToxCast data, consisting of over 600 high-throughput screening (HTS) and high-content screening (HCS) assays, including embryonic stem cells and zebrafish embryos. The observed in vivo toxicity comes from 30 years worth of prenatal guideline studies of rodents and rabbits parsed into a publically available database, ToxRefDB. Due to distinct developmental differences, species specific models of developmental toxicity were built from the HTS data on the 309 ToxCast Phase I chemicals with balanced accuracies over 70%. Unique differences between the species specific models emphasized inflammatory signals in the rabbit model, and the retinoic acid receptor (RAR) and G-protein-coupled receptors (GPCRs) in the rodent model. The in vitro HTS profiles for 700 additional ToxCast Phase II chemicals, including failed pharmaceuticals, alternative plasticizers, and food additives are being used to validate and update the initial predictive models of developmental toxicity. These models have the potential to prioritize chemicals for further targeted toxicity testing and risk assessment, generate hypotheses about mechanistic pathways leading to adverse developmental outcomes, and reduce cost and increase throughput of chemical testing. [This abstract does not necessarily reflect US EPA policy.]