ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Screening the ToxCast Phase 1, Phase 2, and e1k Chemical Libraries for Inhibitors of Iodothyronine Deiodinases.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 76 citations in OpenAlex.
- Review
- Advancing in vitro assessment of iodide uptake inhibition: integrating a novel biotransformation pretreatment step.Archives of toxicology · 2025Article
- Screening the ToxCast Chemical Libraries for Binding to Transthyretin.Chemical research in toxicology · 2024Article
- In Vitro Screening for ToxCast Chemicals Binding to Thyroxine-Binding Globulin.Chemical research in toxicology · 2024Article
- 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 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
- A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment.Open research Europe · 2024Review
- Evaluation of the diphenyl herbicide, oxyfluorfen, for effects on thyroid hormones in the juvenile rat.Current research in toxicology · 2024Article
- Towards translating in vitro measures of thyroid hormone system disruption to in vivo responses in the pregnant rat via a biologically based dose response (BBDR) model.Toxicology and applied pharmacology · 2023Article
- Assessing utility of thyroid in vitro screening assays through comparisons to observed impacts in vivo.Regulatory toxicology and pharmacology : RTP · 2023Review
- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- A biologically based computational model for the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis larvae.Mathematical biosciences · 2023Article
- Combining In Vitro and In Silico New Approach Methods to Investigate Type 3 Iodothyronine Deiodinase Chemical Inhibition Across Species.Environmental toxicology and chemistry · 2023Article
- New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians.Environmental toxicology and chemistry · 2023Review
- Phenol and Phthalate Effects on Thyroid Hormone Levels during Pregnancy: Relying onEnvironmental health perspectives · 2022Article
- Amphibian Metamorphosis Assay: Investigation of the potential effects of five chemicals on the hypothalamic-pituitary thyroid axis of Xenopus laevis.Regulatory toxicology and pharmacology : RTP · 2022Article
- Advances in computational methods along the exposure to toxicological response paradigm.Toxicology and applied pharmacology · 2022Article
- Cross-species comparison of chemical inhibition of human and Xenopus iodotyrosine deiodinase.Aquatic toxicology (Amsterdam, Netherlands) · 2022Article
- Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults.Reviews in endocrine & metabolic disorders · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Deiodinase enzymes play an essential role in converting thyroid hormones between active and inactive forms by deiodinating the pro-hormone thyroxine (T4) to the active hormone triiodothyronine (T3) and modifying T4 and T3 to inactive forms. Chemical inhibition of deiodinase activity has been identified as an important endpoint to include in screening chemicals for thyroid hormone disruption. To address the lack of data regarding chemicals that inhibit the deiodinase enzymes, we developed robust in vitro assays that utilized human deiodinase types 1, 2, and 3 and screened over 1800 unique chemicals from the U.S. EPA's ToxCast phase 1_v2, phase 2, and e1k libraries. Initial testing at a single concentration identified 411 putative deiodinase inhibitors that produced inhibition of 20% or greater in at least 1 of the 3 deiodinase assays, including chemicals that have not previously been shown to inhibit deiodinases. Of these, 228 chemicals produced enzyme inhibition of 50% or greater; these chemicals were further tested in concentration-response to determine relative potency. Comparisons across these deiodinase assays identified 81 chemicals that produced selective inhibition, with 50% inhibition or greater of only 1 of the deiodinases. This set of 3 deiodinase inhibition assays provides a significant contribution toward expanding the limited number of in vitro assays used to identify chemicals with the potential to interfere with thyroid hormone homeostasis. In addition, these results set the groundwork for development and evaluation of structure-activity relationships for deiodinase inhibition, and inform targeted selection of chemicals for further testing to identify adverse outcomes of deiodinase inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.