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).

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).

180626 Thyroid Hormone PFOA PFOS Manuscript Data. This dataset is associated with the following publication: Selano, J., V. Richardson, J. Washington, and C. Mazur. Characterization of non-radiolabeled Thyroxine (T4) uptake in cryopreserved rat hepatocyte suspensions: Pharmacokinetic implications for PFOA and PFOS chemical exposure. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, USA, 58: 230-238, (2019).

This data set is a dose response analysis of two thyroid hormone synthesis disruptors in adult male rats. Data included serum and thyroid gland concentrations of the two chemicals tested, propylthiouracil and methimazole, as well as serum and thyroid gland hormone concentrations. These data were critical for developing a model linking highthroughput assay data on synthesis inhibition to make predictions of thyroid hormone in serum. This dataset is associated with the following publication: Hassan, I., H. El-Masri, J. Ford, A. Brennan, S. Handa, K. Friedman, and M. Gilbert. Extrapolating In Vitro and Ex Vivo Screening Assay Data for Thyroperoxidase Inhibition to Predict Serum Thyroid Hormones in the Rat. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 173(2): 280-292, (2020).

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).

No novel data were reported in association with this product. This dataset is not publicly accessible because: The associated publication is a review/forum-type article. No novel scientific data are reported. All data cited have been previously published elsewhere. It can be accessed through the following means: Not applicable. Format: This article is a review/forum-type article. No novel scientific data are included. This dataset is associated with the following publication: Knapen, D., E. Stinckens, J. Cavallin, G. Ankley, H. Holbech, D. Villeneuve, and L. Vergauwen. Toward an AOP network-based tiered testing strategy for the assessment of thyroid hormone disruption. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, USA, 54(16): 8491-8499, (2020).

This excel spreadsheet contains the resultant data for over from inhibition assays with human Deiodinase 1 screened against the ToxCast Phase 1 chemical library and a few additional chemicals. Over 1800 chemicals were tested in total. It contains the list of chemicals tested and the median, minimum, and maximum inhibition for each chemical screened at 200 µM. Chemicals that gave greater than 50% inhibition were screened in concentration response mode, and the median, min, max inhibition at each concentration for those chemicals are included. Propylthiouracil was used in each plate as a positive control and the concentration-response data for those curves are also included. This dataset is associated with the following publication: Hornung, M., J. Korte, J. Olker, J. Denny, C. Knutsen, P. Hartig, M. Cardon, and S. Degitz. Screening the ToxCast Phase 1 chemical library for inhibition of deiodinase type 1 activity. TOXICOLOGICAL SCIENCES. Society of Toxicology, 162(2): 570-581, (2018).

These data are represented in tables and graphs in the article, "Targeted pathway-based in vivo testing using thyroperoxidase inhibition to evaluate plasma thyroxine as a surrogate metric of metamorphic success in model amphibian Xenopus laevis" by JT Haselman et al. This dataset is associated with the following publication: Haselman, J., J. Olker, P. Kosian, J. Korte, J. Swintek, J. Denny, J. Nichols, J. Tietge, M. Hornung, and S. Degitz. Targeted pathway-based in vivo testing using thyroperoxidase inhibition to evaluate plasma thyroxine as a surrogate metric of metamorphic success in model amphibian Xenopus laevis. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 175(2): 236-250, (2020).

The objective of this study was to develop a medium-throughput organotypic screening assay comprised of reconstructed human thyroid microtissues to quantitatively evaluate the disruptive effects of chemicals on TH production and secretion. Primary human thyroid cells procured from qualified euthyroid donors were analyzed for retention of NK2 homeobox 1 (NKX2-1), Keratin 7 (KRT7), and Thyroglobulin (TG) expression by high-content image analysis to verify enrichment of follicular epithelial cells. A direct comparison of two-dimensional (2D) and three-dimensional (3D) 96-well culture formats was employed to characterize the morphology, differential gene expression, TG production, and TH synthesis over the course of 20 days. This dataset is associated with the following publication: Deisenroth, C., V. Soldatow, J. Ford, W. Stewart, C. Brinkman, E. LeCluyse, D. Macmillan, and R. Thomas. Development of an In Vitro Human Thyroid Microtissue Model for Chemical Screening (ToxSci). TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 174(1): 63-78, (2020).

Data pertaining to a NIS-expressing cell line, FRTL-5 and it's screening capabilities for confirming inhibitors of NIS-mediated iodide uptake. This dataset is associated with the following publication: Buckalew, A., J. Wang, A. Murr, C. Deisenroth, W. Stewart, T. Stoker, and S. Laws. Evaluation of potential sodium-iodide symporter (NIS) inhibitors using a secondary Fischer rat thyroid follicular cell (FRTL-5) radioactive iodide uptake (RAIU) assay. Archives of Toxicology. Springer, New York, NY, USA, 94(3): 873-885, (2020).