Current Availability of Stem Cell-Based In Vitro Methods for Developmental Neurotoxicity (DNT) Testing

Toxicol Sci. 2018 Sep 1;165(1):21-30. doi: 10.1093/toxsci/kfy178.


There is evidence that chemical exposure during development can cause irreversible impairments of the human developing nervous system. Therefore, testing compounds for their developmentally neurotoxic potential has high priority for different stakeholders: academia, industry, and regulatory bodies. Due to the resource-intensity of current developmental neurotoxicity (DNT) in vivo guidelines, alternative methods that are scientifically valid and have a high predictivity for humans are especially desired by regulators. Here, we review availability of stem-/progenitor cell-based in vitro methods for DNT evaluation that is based on the concept of neurodevelopmental process assessment. These test methods are assembled into a DNT in vitro testing battery. Gaps in this testing battery addressing research needs are also pointed out.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animal Testing Alternatives
  • Animals
  • Apoptosis / drug effects
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Embryonic Stem Cells / drug effects*
  • Embryonic Stem Cells / pathology
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / pathology
  • Nervous System / drug effects*
  • Nervous System / embryology
  • Nervous System / growth & development
  • Nervous System / pathology
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / pathology
  • Neurogenesis / drug effects*
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / pathology
  • Toxicity Tests / methods*