ArticleArchives of toxicology2018
Screening the ToxCast phase II libraries for alterations in network function using cortical neurons grown on multi-well microelectrode array (mwMEA) plates.
Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 68 citations in OpenAlex.
- Prioritizing chemicals for developmental neurotoxicity by integrating data from a new approach methods (NAMs) battery covering key cellular events in neurodevelopment.Neurotoxicology · 2026Article
- 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
- Personal air sampling for pesticides in the California San Joaquin Valley.Journal of exposure science & environmental epidemiology · 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
- The environmental neuroactive chemicals list of prioritized substances for human biomonitoring and neurotoxicity testing: A database and high-throughput toxicokinetics approach.Environmental research · 2025Article
- Modulation of CaScientific reports · 2024Article
- Effects of chronic insecticide exposure on neuronal network development in vitro in rat cortical cultures.Archives of toxicology · 2024Article
- Development of an evaluation method for addictive compounds based on electrical activity of human iPS cell-derived dopaminergic neurons using microelectrode array.Addiction biology · 2024Article
- Identification of neural-relevant toxcast high-throughput assay intended gene targets: Applicability to neurotoxicity and neurotoxicant putative molecular initiating events.Neurotoxicology · 2024Review
- How neurobehavior and brain development in alternative whole-organism models can contribute to prediction of developmental neurotoxicity.Neurotoxicology · 2024Review
- Development of a new hazard scoring system in primary neuronal cell cultures for drug-induced acute neuronal toxicity identification in early drug discovery.Frontiers in pharmacology · 2024Article
- Identification of neurotoxicology (NT)/developmental neurotoxicology (DNT) adverse outcome pathways and key event linkages with in vitro DNT screening assays.Neurotoxicology · 2023Review
- Paths to cheminformatics: Q&A with Ann M. Richard.Journal of cheminformatics · 2023Article
- Assaying Spontaneous Network Activity and Cellular Viability Using Multi-Well Microelectrode Arrays.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Current status and future directions for a neurotoxicity hazard assessment framework that integratesComputational toxicology (Amsterdam, Netherlands) · 2022Article
- Integrating Data From In Vitro New Approach Methodologies for Developmental Neurotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Prediction of the Neurotoxic Potential of Chemicals Based on Modelling of Molecular Initiating Events Upstream of the Adverse Outcome Pathways of (Developmental) Neurotoxicity.International journal of molecular sciences · 2022Article
- The Future of 3D Brain Cultures in Developmental Neurotoxicity Testing.Frontiers in toxicology · 2022Review
- A human stem cell-derived test system for agents modifying neuronal N-methyl-D-aspartate-type glutamate receptor CaArchives of toxicology · 2021Article
- Development of an objective index, neural activity score (NAS), reveals neural network ontogeny and treatment effects on microelectrode arrays.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Methods are needed for rapid screening of environmental compounds for neurotoxicity, particularly ones that assess function. To demonstrate the utility of microelectrode array (MEA)-based approaches as a rapid neurotoxicity screening tool, 1055 chemicals from EPA's phase II ToxCast library were evaluated for effects on neural function and cell health. Primary cortical networks were grown on multi-well microelectrode array (mwMEA) plates. On day in vitro 13, baseline activity (40 min) was recorded prior to exposure to each compound (40 µM). Changes in spontaneous network activity [mean firing rate (MFR)] and cell viability (lactate dehydrogenase and CellTiter Blue) were assessed within the same well following compound exposure. Following exposure, 326 compounds altered (increased or decreased) normalized MFR beyond hit thresholds based on 2× the median absolute deviation of DMSO-treated wells. Pharmaceuticals, pesticides, fungicides, chemical intermediates, and herbicides accounted for 86% of the hits. Further, changes in MFR occurred in the absence of cytotoxicity, as only eight compounds decreased cell viability. ToxPrint chemotype analysis identified several structural domains (e.g., biphenyls and alkyl phenols) significantly enriched with MEA actives relative to the total test set. The top 5 enriched ToxPrint chemotypes were represented in 26% of the MEA hits, whereas the top 11 ToxPrints were represented in 34% of MEA hits. These results demonstrate that large-scale functional screening using neural networks on MEAs can fill a critical gap in assessment of neurotoxicity potential in ToxCast assay results. Further, a data-mining approach identified ToxPrint chemotypes enriched in the MEA-hit subset, which define initial structure-activity relationship inferences, establish potential mechanistic associations to other ToxCast assay endpoints, and provide working hypotheses for future studies.
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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.