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).

How to access data for "Decrane R, Stoker T, Murr A, Ford J, El-Masri H. Cross species extrapolation of the disruption of thyroid hormone synthesis by oxyfluorfen using in vitro data, physiologically based pharmacokinetic (PBPK), and thyroid hormone kinetics models. Curr Res Toxicol. 2023 Nov 23;5:100138. doi: 10.1016/j.crtox.2023.100138. PMID: 38074188; PMCID: PMC10697989.". This dataset is not publicly accessible because: N/A. It can be accessed through the following means: Data will be made available on request from Hisham El-Masri (el-masri.hisham@epa.gov). Format: N/A. This dataset is associated with the following publication: Decrane, R., T. Stoker, A. Murr, J. Ford, and H. El-Masri. Cross species extrapolation of the disruption of thyroid hormone synthesis by oxyfluorfen using in vitro data, physiologically based pharmacokinetic (PBPK), and thyroid hormone kinetics models. Current Research in Toxicology. Elsevier B.V., Amsterdam, NETHERLANDS, 5: 100138, (2023).

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).

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).

Dataset for Foley et al. 'Technical evaluation and standardization of the human thyroid microtissue assay'; Toxicological Sciences, Vol 199, Issue 1, pg 89-107, kfae014 May 2024. DOI https://doi.org/10.1093/toxsci/kfae014. This dataset is associated with the following publication: Foley, B., K. Breaux, J. Gamble, S. Lynn, R. Thomas, and C. Deisenroth. Technical Evaluation and Standardization of the Human Thyroid Microtissue Assay. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 199(1): 89-107, (2024).

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).

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).

This dataset was generated to support parameterization of a larval amphibian thyroid axis computational model. Specifically, plasma iodine levels were determined not only to inform a concentration value for model parameter specification in the model, but also to support the notion that aquatic and terrestrial species should be considered substantially different with regard to circulating iodide levels. Other computational model physical parameters were informed by evaluating Xenopus laevis thyroid gland histological images for morphological features including thyroid follicular cell numbers and areas. This dataset is associated with the following publication: Haselman, J., J. Nichols, K. Mattingly, M. Hornung, and S. Degitz. A biologically based computational model for the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis larvae. MATHEMATICAL BIOSCIENCES. Elsevier Science Ltd, New York, NY, USA, 362: 109021, (2023).

This dataset was generated to support parameterization of a larval amphibian thyroid axis computational model. Specifically, plasma iodine levels were determined not only to inform a concentration value for model parameter specification in the model, but also to support the notion that aquatic and terrestrial species should be considered substantially different with regard to circulating iodide levels. Other computational model physical parameters were informed by evaluating Xenopus laevis thyroid gland histological images for morphological features including thyroid follicular cell numbers and areas. This dataset is associated with the following publication: Haselman, J., J. Nichols, K. Mattingly, M. Hornung, and S. Degitz. A biologically based computational model for the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis larvae. MATHEMATICAL BIOSCIENCES. Elsevier Science Ltd, New York, NY, USA, 362: 109021, (2023).