ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors Within the ToxCast Phase I and II Chemical Libraries.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed, 132 citations in OpenAlex.
- Resorcinol in Dermatology: Reassessing a Legacy Topical Therapy for Contemporary Clinical Use.Dermatology (Basel, Switzerland) · 2026Review
- Classification of Thyroid Peroxidase (TPO) Inhibitors Using Transfer Learning with SMILES Embeddings.Chemical research in toxicology · 2026Article
- In vitro thyroperoxidase inhibition assessment by LC-ICP-MS-based L-tyrosine iodination assay: comparison with Amplex Ultrared assay and its modifications.Archives of toxicology · 2026Article
- Epidemiological relevant effect biomarkers for thyroid hormone system related adverse outcome pathways: a literature review.Frontiers in pharmacology · 2026Review
- Maternal exposure to the thyroperoxidase-inhibiting pesticide amitrole induces hypothyroidism and developmental neurotoxicity in the rat brain.Frontiers in endocrinology · 2026Article
- Review
- Advancing in vitro assessment of iodide uptake inhibition: integrating a novel biotransformation pretreatment step.Archives of toxicology · 2025Article
- Personal air sampling for pesticides in the California San Joaquin Valley.Journal of exposure science & environmental epidemiology · 2025Article
- Thyroid Stimulatory Activity ofNutrients · 2025Article
- In Vitro Screening for ToxCast Chemicals Binding to Thyroxine-Binding Globulin.Chemical research in toxicology · 2024Article
- Two novel in vitro assays to screen chemicals for their capacity to inhibit thyroid hormone transmembrane transporter proteins OATP1C1 and OAT4.Archives of toxicology · 2024Article
- Community-Engaged Research and the Use of Open Access ToxVal/ToxRef In Vivo Databases and New Approach Methodologies (NAM) to Address Human Health Risks From Environmental Contaminants.Birth defects research · 2024Article
- In vitro assessment of thyroid peroxidase inhibition by chemical exposure: comparison of cell models and detection methods.Archives of toxicology · 2024Article
- Article
- Technical evaluation and standardization of the human thyroid microtissue assay.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- A Comparison of In Vitro Points of Departure with Human Blood Levels for Per- and Polyfluoroalkyl Substances (PFAS).Toxics · 2024Article
- In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles.Scientific reports · 2024Article
- In vitro screening of per- and polyfluorinated substances (PFAS) for interference with seven thyroid hormone system targets across nine assays.Toxicology in vitro : an international journal published in association with BIBRA · 2024Article
- Evaluation of the diphenyl herbicide, oxyfluorfen, for effects on thyroid hormones in the juvenile rat.Current research in toxicology · 2024Article
- Low thyroxine serves as an upstream regulator of ecophysiological adaptations in Ansell's mole-rats.Frontiers in endocrinology · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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