ArticleToxicological sciences : an official journal of the Society of Toxicology2022
Integrating Data From In Vitro New Approach Methodologies for Developmental Neurotoxicity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Integrating mechanistic data to contextualize in vivo apical observations using the developmental neurotoxicity in vitro battery.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Timing of exposure impacts how organophosphorus pesticides affect the developing brain in the planarian Dugesia japonica.Archives of toxicology · 2026Article
- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Prioritizing chemicals for developmental neurotoxicity by integrating data from a new approach methods (NAMs) battery covering key cellular events in neurodevelopment.Neurotoxicology · 2026Article
- Comparison of physiologically based pharmacokinetic modeling platforms for developmental neurotoxicity in vitro to in vivo extrapolation.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays.Frontiers in toxicology · 2026Review
- Leveraging the developmental neurotoxicityFrontiers in toxicology · 2026Article
- Interpretation of in vitro concentration-response data for risk assessment and regulatory decision-making: Report from the 2022 IWGT quantitative analysis expert working group meeting.Environmental and molecular mutagenesis · 2025Review
- Application of a high-density microelectrode array assay using a 3D human iPSC-derived brain microphysiological system model for in vitro neurotoxicity screening of environmental compounds.Archives of toxicology · 2025Article
- Modeling the developing nervous system: a neuroscience perspective on the use of new approach methodologies in developmental neurotoxicity testing.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- A comparative study of biostatistical pipelines for benchmark concentration modeling ofComputational toxicology (Amsterdam, Netherlands) · 2025Article
- Bioactivity of the ubiquitous tire preservative 6PPD and degradant, 6PPD-quinone in fish- and mammalian-based assays.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- A data analysis approach for locomotor behavioral responses in developmentally exposed zebrafish.NAM journal · 2025Article
- Article
- Neural organoids incorporating microglia to assess neuroinflammation and toxicities induced by known developmental neurotoxins.Current research in toxicology · 2025Article
- Advancing human health risk assessment: the role of new approach methodologies.Frontiers in toxicology · 2025Review
- Inhibition of Neural Crest Cell Migration by Strobilurin Fungicides and Other Mitochondrial Toxicants.Cells · 2024Article
- Investigation of Peroxisome Proliferator-Activated Receptor Genes as Requirements for Visual Startle Response Hyperactivity in Larval Zebrafish Exposed to Structurally Similar Per- and Polyfluoroalkyl Substances (PFAS).Environmental health perspectives · 2024Article
- Article
- Investigating open access new approach methods (NAM) to assess biological points of departure: A case study with 4 neurotoxic pesticides.Current research in toxicology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In vivo developmental neurotoxicity (DNT) testing is resource intensive and lacks information on cellular processes affected by chemicals. To address this, DNT new approach methodologies (NAMs) are being evaluated, including: the microelectrode array neuronal network formation assay; and high-content imaging to evaluate proliferation, apoptosis, neurite outgrowth, and synaptogenesis. This work addresses 3 hypotheses: (1) a broad screening battery provides a sensitive marker of DNT bioactivity; (2) selective bioactivity (occurring at noncytotoxic concentrations) may indicate functional processes disrupted; and, (3) a subset of endpoints may optimally classify chemicals with in vivo evidence for DNT. The dataset was comprised of 92 chemicals screened in all 57 assay endpoints sourced from publicly available data, including a set of DNT NAM evaluation chemicals with putative positives (53) and negatives (13). The DNT NAM battery provides a sensitive marker of DNT bioactivity, particularly in cytotoxicity and network connectivity parameters. Hierarchical clustering suggested potency (including cytotoxicity) was important for classifying positive chemicals with high sensitivity (93%) but failed to distinguish patterns of disrupted functional processes. In contrast, clustering of selective values revealed informative patterns of differential activity but demonstrated lower sensitivity (74%). The false negatives were associated with several limitations, such as the maximal concentration tested or gaps in the biology captured by the current battery. This work demonstrates that this multi-dimensional assay suite provides a sensitive biomarker for DNT bioactivity, with selective activity providing possible insight into specific functional processes affected by chemical exposure and a basis for further research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.