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Related Experiment Video

Updated: Dec 29, 2025

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
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Systems Modeling of Developmental Vascular Toxicity.

Katerine S Saili1, Jill A Franzosa1, Nancy C Baker1,2

  • 1National Center for Computational Toxicology (NCCT), Office of Research and Development (ORD), U.S. Environmental Protection Agency (USEPA) Research Triangle Park NC 27711.

Current Opinion in Toxicology
|February 8, 2020
PubMed
Summary
This summary is machine-generated.

High-throughput screening (HTS) assays predict developmental toxicity by assessing chemical effects on embryonic vascular development. This approach integrates data from in silico and in vitro systems to improve chemical hazard characterization.

Keywords:
5HPP-33Adverse outcome pathwayTNP-470Tox21ToxCastangiogenesis

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Area of Science:

  • Developmental toxicology
  • Systems toxicology
  • Chemical hazard assessment

Background:

  • Over 80,000 chemicals in commerce require robust hazard assessments.
  • Assessing chemical effects on human development is complex, needing to capture dynamic events.
  • High-throughput screening (HTS) assays and systems toxicology models are advancing toxicity testing.

Purpose of the Study:

  • To develop and validate a model for predicting developmental vascular toxicity using ToxCast HTS data.
  • To integrate in silico and in vitro data within an Adverse Outcome Pathway (AOP) framework.
  • To investigate the modes of action of angiogenesis inhibitors in developmental systems.

Main Methods:

  • Constructed an AOP (Aop43) for developmental toxicity via embryonic vascular disruption.
  • Generated quantitative predictions of developmental vascular toxicity from ToxCast HTS data for 38 chemicals.
  • Compared HTS predictions with functional vascular development assays in cell systems, virtual tissues, and model organisms.

Main Results:

  • HTS predictions showed capacity to identify putative vascular disrupting compounds (pVDCs).
  • Results demonstrated confidence in predicting adverse developmental outcomes from in vitro HTS data.
  • Integrated AOPs and developmental systems toxicology to analyze specific modes of action for two inhibitors.

Conclusions:

  • HTS data and AOPs enhance the prediction of chemical developmental toxicity.
  • Systems toxicology models incorporating mechanistic data improve understanding of chemical effects.
  • This integrated approach supports more accurate chemical hazard characterization for developmental outcomes.