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Predictive developmental toxicity with pluripotent stem cell models and ToxCast/Tox21 assay batteries (BDRP)
Citation:
Knudsen, T. Predictive developmental toxicity with pluripotent stem cell models and ToxCast/Tox21 assay batteries (BDRP). Society for Birth Defects Research and Prevention 61st Annual Meeting, NA, Virtual, June 24 - July 01, 2021. https://doi.org/10.23645/epacomptox.14892927
Impact/Purpose:
This presentation will be given at the workshop entitled "New Frontiers in Developmental Toxicity Testing for Environmental Chemicals" at the 2021 annual meeting of the Society for Birth Defects Research and Prevention (formerly the Teratology Society).
Description:
Assessing developmental toxicity during pregnancy has a critical role in setting health and environmental policy. In vitro assays and in silico models that reflect key aspects of embryo-fetal development will be indispensable for NAM-based detection of developmental hazard potential in animal models of human relevance (e.g., pregnant rats, rabbits). High-throughput screening (HTS) and other in vitro platforms using pluripotent stem cell (PSC) lines established from the embryoblast (mouse, human) can recapitulate some of the biology driving embryogenesis during the period covered by guideline prenatal studies (e.g., OECD TG 414). Computational models built on biological knowledge of embryogenesis can extend data-driven models to predict thresholds of developmental toxicity potential or inform mechanistic pathways and processes. This presentation will provide an update on the use of pluripotent and differentiating stem cell models for predictive modeling of developmental toxicity. Learning objectives will include: (i) a compilation of various stem cell modalities for developmental toxicity; (ii) synopsis of an ongoing international effort (Europe, Japan, USA) scoping the performance of stem cell models for predictive developmental toxicity in the published literature; (iii) performance-based evaluation of stem cell assays in ToxCast/Tox21 for threshold-based determinations of developmental toxicity in pregnant animal studies; (iv) improvements in assay sensitivity with deep learning models utilizing >1000 assays from the ToxCast/Tox21 assay portfolio; and (v) applications to in silico toxicodynamic models in a virtual embryo platform. This abstract does not represent the views of the Agency.
URLs/Downloads:
DOI: Predictive developmental toxicity with pluripotent stem cell models and ToxCast/Tox21 assay batteries (BDRP)
BDRP_NAMS_KNUDSEN_V2.PDF (PDF, NA pp, 4025.406 KB, about PDF)