An industry perspective: A streamlined screening strategy using alternative models for chemical assessment of developmental neurotoxicity

Neurotoxicology
Jinpeng LiM Sue Marty

Abstract

Developmental neurotoxicity (DNT) is an important endpoint for the safety assessment of chemicals. However, the current in vivo animal model for DNT assessment is resource-intensive and may not fully capture all mechanisms that may be relevant to DNT in humans. As a result, there is a growing need for more reliable, time- and cost-efficient approaches for DNT evaluation. Toward this end, many stem/progenitor cell-based in vitro models and alternative organism-based models are becoming available with the potential for high throughput screening of DNT. Meanwhile, with advances in the knowledgebase of DNT molecular mechanisms and the identification of DNT-related adverse outcome pathways (AOP) there is potential to develop a mechanism-based integrated testing strategy for DNT assessment. This review summarizes the state of science regarding currently available human stem/progenitor cell-based in vitro models and alternative organism-based models that could be used for DNT testing. In addition, the current knowledge regarding DNT AOPs is reviewed to identify common key events that could serve as critical endpoints to assess multiple AOPs that underlie DNT. Following the identification of common key events, a streamlined strategy is...Continue Reading

Citations

Jun 13, 2020·Critical Reviews in Toxicology·Deepika DeepikaVikas Kumar
Aug 25, 2019·Archives of Toxicology·Nicoleta SpinuAndrew P Worth
May 20, 2020·Archives of Toxicology·Nicoleta SpinuAndrew P Worth
Aug 3, 2021·Oxidative Medicine and Cellular Longevity·Yuhei NishimuraHiroaki Aoyama
Oct 7, 2021·Environmental Health Perspectives·Heather B PatisaulHeather M Stapleton

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