Strategies to improve the regulatory assessment of developmental neurotoxicity (DNT) using in vitro methods

Toxicology and Applied Pharmacology
Anna K Bal-PriceAndrew Worth

Abstract

Currently, the identification of chemicals that have the potential to induce developmental neurotoxicity (DNT) is based on animal testing. Since at the regulatory level, systematic testing of DNT is not a standard requirement within the EU or USA chemical legislation safety assessment, DNT testing is only performed in higher tiered testing triggered based on chemical structure activity relationships or evidence of neurotoxicity in systemic acute or repeated dose toxicity studies. However, these triggers are rarely used and, in addition, do not always serve as reliable indicators of DNT, as they are generally based on observations in adult rodents. Therefore, there is a pressing need for developing alternative methodologies that can reliably support identification of DNT triggers, and more rapidly and cost-effectively support the identification and characterization of chemicals with DNT potential. We propose to incorporate mechanistic knowledge and data derived from in vitro studies to support various regulatory applications including: (a) the identification of potential DNT triggers, (b) initial chemical screening and prioritization, (c) hazard identification and characterization, (d) chemical biological grouping, and (e) asses...Continue Reading

Citations

Jul 10, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ellen FritscheJulia Tigges
Nov 27, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Magdalini SachanaAndrea Terron
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Jun 5, 2020·International Journal of Molecular Sciences·Diana LupuJoëlle Rüegg
Aug 16, 2018·Scientific Reports·Shigeru YamadaYasunari Kanda
Aug 25, 2019·Archives of Toxicology·Nicoleta SpinuAndrew P Worth
Jan 1, 2019·Environmental Sciences Europe·J B LegradiH Hollert
Feb 26, 2020·Environmental Health : a Global Access Science Source·Francesca PistollatoAnna Bal-Price
Apr 9, 2020·Frontiers in Neurology·Linda OttoboniGianvito Martino
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Apr 3, 2020·Chemical Research in Toxicology·William K Boyes, Christoph van Thriel

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