{"accessLevel": "public", "bureauCode": ["020:00"], "contactPoint": {"fn": "Steven Simmons", "hasEmail": "mailto:simmons.steve@epa.gov"}, "description": "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. \n\nThis dataset is associated with the following publication:\nPaul-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).", "distribution": [{"accessURL": "https://gaftp.epa.gov/COMPTOX/NCCT_Publication_Data/FriedmanPaul_K/2016_TPO_ToxCast_ToxSci", "title": "https://gaftp.epa.gov/COMPTOX/NCCT_Publication_Data/FriedmanPaul_K/2016_TPO_ToxCast_ToxSci"}, {"downloadURL": "https://pasteur.epa.gov/uploads/97/Figures%20and%20Tables_v10.docx", "mediaType": "application/vnd.openxmlformats-officedocument.wordprocessingml.document", "title": "Figures and Tables_v10.docx"}], "identifier": "A-z35j-97", "keyword": ["Thyroperoxidase", "ToxCast", "chemical safety for sustainablity", "chemical safety research", "endocrine disruption", "high-throughput toxicology"], "license": "https://pasteur.epa.gov/license/sciencehub-license.html", "modified": "2016-04-01", "programCode": ["020:095"], "publisher": {"name": "U.S. EPA Office of Research and Development (ORD)", "subOrganizationOf": {"name": "U.S. Environmental Protection Agency", "subOrganizationOf": {"name": "U.S. Government"}}}, "references": ["https://doi.org/10.1093/toxsci/kfw034"], "rights": null, "title": "Data from Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries "}