High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the U.S. Environmental Protection Agency ToxCast screening assay portfolio. To fill 1 critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast phase I and II chemical libraries, comprised of 1074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single-concentration screen were retested in concentration-response. Due to high false-positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed 2 additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using guaiacol as a substrate to confirm the activity profiles of putative TPO inhibitors. This effort represents the most extensive TPO inhibition screening campaign to date and illustrates a tiered screening approach that focuses resources, maximizes assay throughput, and reduces animal use. This dataset is associated with the following publication: Paul-Friedman, K., E.D. Watt , M.W. Hornung , J.M. Hedge , R.S. Judson , K.M. Crofton , K.A. Houck , and S.O. Simmons. (TOXICOLOGICAL SCIENCES) Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries. TOXICOLOGICAL SCIENCES. Society of Toxicology, 1-59, (2016).

All tables, plus the data for generating figures presented in the manuscript "High-Throughput Screening and Chemotype-Enrichment Analysis of ToxCast Phase II Chemicals Evaluated for Human Sodium-Iodide Symporter (NIS) Inhibition". This dataset is associated with the following publication: Wang, J., D. Hallinger, A. Murr, A. Buckalew, R. Lougee, A. Richard, S. Laws, and T. Stoker. High-Throughput Screening and Chemotype-Enrichment Analysis of ToxCast Phase II Chemicals Evaluated for Human Sodium-Iodide Symporter (NIS) Inhibition. ENVIRONMENT INTERNATIONAL. Elsevier B.V., Amsterdam, NETHERLANDS, 377-386, (2019).

Data set includes optimized assay parameters and kinetic characterization for xenopus laevis deiodinase type 3 enzyme, and inhibition activity of 352 ToxCast chemicals against this enzyme. This dataset is associated with the following publication: Mayasich, S., J. Korte, J. Denny, P. Hartig, J. Olker, P. Degoey, J. O'Flanagan, S. Degitz, and M. Hornung. Xenopus laevis and human type 3 iodothyronine deiodinase enzyme cross-species sensitivity to inhibition by ToxCast chemicals. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 73: 105141, (2021).

Data pertaining to a NIS-expressing cell line, hNIS-HEK293T-EPA, and its screening capabilities for determining inhibitors of NIS-mediated iodide uptake. This dataset is associated with the following publication: Hallinger, D., A. Murr, A. Buckalew, S. Simmons, T. Stoker, and S. Laws. Development of a Screening Approach to Detect Thyroid Disrupting Chemicals that Inhibit the Human Sodium/Iodide Symporter (NIS). TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, USA, 66-78, (2017).

ToxCast is used as a cost-effective approach for efficiently prioritizing the toxicity testing of thousands of chemicals. It uses data from state-of-the-art high throughput screening (HTS) bioassay and builds computational models to forecast potential chemical toxicity in humans. ToxRefDB stores data related to ToxCast.

ToxCast is used as a cost-effective approach for efficiently prioritizing the toxicity testing of thousands of chemicals. It uses data from state-of-the-art high throughput screening (HTS) bioassay and builds computational models to forecast potential chemical toxicity in humans. ToxRefDB stores data related to ToxCast.

Dataset for "Combining in vitro and in silico New Approach Methods to investigate type 3 iodothyronine deiodinase chemical inhibition across species". This dataset is associated with the following publication: Mayasich, S., M. Goldsmith, K. Mattingly, and C. Lalone. Combining In Vitro and In Silico New Approach Methods to Investigate Type 3 Iodothyronine Deiodinase Chemical Inhibition Across Species. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(5): 1032-1048, (2023).

Supplementary data for "Stephanie A. Eytcheson, Jennifer H. Olker, Katie Paul Friedman, Michael W. Hornung, Sigmund J. Degitz, Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo, Regulatory Toxicology and Pharmacology, Volume 144, 2023, 105491, ISSN 0273-2300, https://doi.org/10.1016/j.yrtph.2023.105491.". Portions of this dataset are inaccessible because: N/A. They can be accessed through the following means: N/A. Format: The data used in this analysis are from publicly available sources and are cited in the references and/or the supplemental files. This dataset is associated with the following publication: Eytcheson, S., J. Olker, K. Friedman, M. Hornung, and S. Degitz. Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo. REGULATORY TOXICOLOGY AND PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 144: 105491, (2023).

This excel file contains 7 tabs, each tabs contains the data for one specific figure in the paper. Description of the data and column names is also provided in each tab. This dataset is associated with the following publication: Wang, J., D. Hallinger, A. Murr, A. Buckalew, S. Simmons, S. Laws, and T. Stoker. High-Throughput Screening and Quantitative Chemical Ranking for Sodium Iodide Symporter Inhibitors in ToxCast Phase 1 Chemical Library. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 52(9): 5417-5426, (2018).

The ToxCast program has generated in vitro screening data on over a thousand chemicals to assess potential disruption of important biological processes and assist in hazard identification and chemical testing prioritization. Few results have been reported for complex mixtures. To extend these ToxCast efforts to mixtures, we tested extracts from 30 organically grown fruits and vegetables in concentration-response in the BioMAP® assays. BioMAP systems use human primary cells primed with endogenous pathway activators to identify phenotypic perturbations related to proliferation, inflammation, immunomodulation, and tissue remodeling. This dataset is associated with the following publication: Wetmore, B., R. Clewell, B. Cholewa, B. Parks, S. Pendse, M. Black, K. Mansouri, S. Haider, E. Berg, R. Judson, K. Houck, M. Martin, H. Clewell III, M. Andersen, R. Thomas, and P. McMullen. Assessing Bioactivity-Exposure Profiles of Fruits and Vegetables in the BioMAP Profiling System. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, USA, 54: 41-57, (2019).