Evidence map›Paper›PMID 28973696›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2017

Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework.

Iman Hassan, Hisham El-Masri, Patricia A Kosian, Jermaine Ford, Sigmund J Degitz, Mary E Gilbert

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
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  9. Ammonium perchlorate: serum dosimetry, neurotoxicity, and resilience of the neonatal rat thyroid system.Toxicological sciences : an official journal of the Society of Toxicology · 2024
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  10. Article
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  15. 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 · 2023
    Article
  16. Article
  17. 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 · 2022
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  18. Article
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  20. Towards a qAOP framework for predictive toxicology - Linking data to decisions.Computational toxicology (Amsterdam, Netherlands) · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Iman HassanToxicity Assessment Division.
Hisham El-MasriIntegrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709.
Patricia A KosianMid-Continent Ecology Division, National Health and Environmental Effects Research Lab, US Environmental Protection Agency, Duluth, Minnesota 55804.
Jermaine FordAnalytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27709.
Sigmund J DegitzMid-Continent Ecology Division, National Health and Environmental Effects Research Lab, US Environmental Protection Agency, Duluth, Minnesota 55804.
Mary E GilbertToxicity Assessment Division.
Environmental Protection Agency · US

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

Adequate levels of thyroid hormone (TH) are needed for proper brain development, deficiencies may lead to adverse neurologic outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures and decline in serum TH resulting in neurodevelopmental impairment is poorly understood. The present study developed a quantitative adverse outcome pathway where serum thyroxin (T4) reduction following inhibition of thyroperoxidase in the thyroid gland are described and related to deficits in fetal brain TH and the development of a brain malformation, cortical heterotopia. Pregnant rats were exposed to 6-propylthiouracil (PTU 0, 0.1, 0.5, 1, 2, or 3 parts per million [ppm]) from gestational days 6-20, sequentially increasing PTU concentrations in maternal thyroid gland and serum as well as in fetal serum. Dams exposed to 0.5 ppm PTU and higher exhibited dose-dependent decreases in thyroidal T4. Serum T4 levels in the dam were significantly decreased with exposure to 2 and 3 ppm PTU. In the fetus, T4 decrements were first observed at a lower dose of 0.5 ppm PTU. Based on these data, fetal brain T4 levels were estimated from published literature sources, and quantitatively linked to increases in the size of the heterotopia present in the brains of offspring. These data show the potential of in vivo assessments and computational descriptions of biologic responses to predict the development of this structural brain malformation and use of quantitative adverse outcome pathway approach to evaluate brain deficits that may result from exposure to other TH disruptors.

Indexed as

Adverse Outcome PathwaysPrenatal Exposure Delayed EffectsAnimalsBiomarkersBrainComputer SimulationDose-Response Relationship, DrugEndocrine DisruptorsEnzyme InhibitorsFemaleGestational AgeIodide PeroxidaseMalformations of Cortical DevelopmentMaternal ExposurePregnancyPropylthiouracilBiomarkersEndocrine DisruptorsEnzyme InhibitorsIodide PeroxidasePropylthiouracilThyroxinebrain developmentqAOPthyroid hormonethyroperoxidase

Identifiers

PMID28973696
PMCPMC10623382
OpenAlexW2748279366

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.