ArticleToxicological sciences : an official journal of the Society of Toxicology2021
Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Disruption of the thyroid hormone system and patterns of altered thyroid hormones after gestational chemical exposures in rodents - a systematic review.Frontiers in endocrinology · 2023Pooled it
- Maternal exposure to the thyroperoxidase-inhibiting pesticide amitrole induces hypothyroidism and developmental neurotoxicity in the rat brain.Frontiers in endocrinology · 2026Article
- Maternal, fetal, and neonatal toxicity and potency estimates of perfluorohexane sulfonate (PFHxS) from oral maternal exposure in the Sprague-Dawley rat.Toxicology · 2025Article
- Gestational and Lactation Exposure to Perfluorohexanoic Acid Results in Sex-Specific Changes in the Cerebellum in Mice.International journal of molecular sciences · 2025Article
- Article
- Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency.Journal of toxicologic pathology · 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
- The pollutant perfluorohexane sulfonate (PFHxS) reduces serum thyroxine but does not alter thyroid action in the postnatal rat brain.Environment international · 2024Article
- Ammonium perchlorate: serum dosimetry, neurotoxicity, and resilience of the neonatal rat thyroid system.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Thyroid Hormone Metabolites Quantified in Pup and Adult Rat Cerebellum, Cortex and Whole-Brain Samples Using an Automated Online SPE-LC-MS/MS Method.Metabolites · 2024Article
- Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital.Current research in toxicology · 2024Article
- Perfluorooctanesulfonic acid (PFOS) disrupts cadherin-16 in the developing rat thyroid gland.Current research in toxicology · 2024Article
- Structural Malformations in the Neonatal Rat Brain Accompany Developmental Exposure to Ammonium Perchlorate.Toxics · 2023Article
- Dose additive maternal and offspring effects of oral maternal exposure to a mixture of three PFAS (HFPO-DA, NBP2, PFOS) during pregnancy in the Sprague-Dawley rat.The Science of the total environment · 2023Article
- Reducing uncertainties in quantitative adverse outcome pathways by analysis of thyroid hormone in the neonatal rat brain.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- High-Throughput Screening of ToxCast PFAS Chemical Library for Potential Inhibitors of the Human Sodium Iodide Symporter.Chemical research in toxicology · 2023Article
- Cumulative maternal and neonatal effects of combined exposure to a mixture of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) during pregnancy in the Sprague-Dawley rat.Environment international · 2022Article
- Gestational Exposure to Perchlorate in the Rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Developmental toxicity of Nafion byproduct 2 (NBP2) in the Sprague-Dawley rat with comparisons to hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) and perfluorooctane sulfonate (PFOS).Environment international · 2022Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Many xenobiotics are identified as potential thyroid disruptors due to their action to reduce circulating levels of thyroid hormone, most notably thyroxine (T4). Developmental neurotoxicity is a primary concern for thyroid disrupting chemicals yet correlating the impact of chemically induced changes in serum T4 to perturbed brain development remains elusive. A number of thyroid-specific neurodevelopmental assays have been proposed, based largely on the model thyroid hormone synthesis inhibitor propylthiouracil (PTU). This study examined whether thyroid disrupting chemicals acting distinct from synthesis inhibition would result in the same alterations in brain as expected with PTU. The perfluoroalkyl substance perfluorohexane sulfonate (50 mg/kg/day) and the antimicrobial Triclosan (300 mg/kg/day) were administered to pregnant rats from gestational day 6 to postnatal day (PN) 21, and a number of PTU-defined assays for neurotoxicity evaluated. Both chemicals reduced serum T4 but did not increase thyroid stimulating hormone. Both chemicals increased expression of hepatic metabolism genes, while thyroid hormone-responsive genes in the liver, thyroid gland, and brain were largely unchanged. Brain tissue T4 was reduced in newborns, but despite persistent T4 reductions in serum, had recovered in the PN6 pup brain. Neither treatment resulted in a low dose PTU-like phenotype in either brain morphology or neurobehavior, raising questions for the interpretation of serum biomarkers in regulatory toxicology. They further suggest that reliance on serum hormones as prescriptive of specific neurodevelopmental outcomes may be too simplistic and to understand thyroid-mediated neurotoxicity we must expand our thinking beyond that which follows thyroid hormone synthesis 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.