Evidence map›Paper›PMID 36075192›Full record

ArticleNeuroendocrinology2023

Impacts of Gestational FireMaster 550 Exposure on the Neonatal Cortex Are Sex Specific and Largely Attributable to the Organophosphate Esters.

Shannah K Witchey, Michael G Doyle, Jacob D Fredenburg, Genevieve St Armour, Brian Horman, Melanie T Odenkirk, David L Aylor, Erin S Baker, Heather B Patisaul

Open access · greenAbstract read
In one paragraph

Article in Neuroendocrinology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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  8. A mixture of organophosphate esters sex-specifically impacts monocyte-macrophages in Sprague-Dawley rats.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  9. Article
  10. Review
  11. Impact of exposure to a mixture of organophosphate esters on the adrenal glands of Sprague Dawley rats.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Article
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  18. Article
  19. Maternal organophosphate flame retardant exposure alters the developing mesencephalic dopamine system in fetal rat.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    Article
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

9 authors at 1 institution in 1 country.

Shannah K WitcheyDepartment of Biological Sciences, NC State University, Raleigh, North Carolina, USA.
Michael G DoyleDepartment of Chemistry, NC State University, Raleigh, North Carolina, USA.
Jacob D FredenburgDepartment of Biological Sciences, NC State University, Raleigh, North Carolina, USA.
Genevieve St ArmourDepartment of Biological Sciences, NC State University, Raleigh, North Carolina, USA.
Brian HormanDepartment of Biological Sciences, NC State University, Raleigh, North Carolina, USA.
Melanie T OdenkirkDepartment of Chemistry, NC State University, Raleigh, North Carolina, USA.
David L AylorDepartment of Biological Sciences, NC State University, Raleigh, North Carolina, USA.
Erin S BakerDepartment of Chemistry, NC State University, Raleigh, North Carolina, USA.
Heather B PatisaulCenter for Human Health and the Environment, NC State University, Raleigh, North Carolina, USA.
North Carolina State University · US

Funding

Single cell, multi-parametric high throughput platform to classify endocrine disruptor potential of mixturesP42ES027704 · NIEHS · TEXAS A&M UNIVERSITY · PI Efstratios Pistikopoulos · 2017 to 2026
$21.2M
Translational Research Support CoreP30ES025128 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Sue Fenton · 2015 to 2026
$18.3M
Uncovering the Mechanisms of PFAS-induced ImmunotoxicityP42ES031009 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI PLANCHART, ANTONIO J. · 2020 to 2024
$9.3M
Systems Toxicogenomics of Endocrine Disrupting Chemicals in BrainU01ES026717 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI AYLOR, DAVID LAWRENCE · 2016 to 2019
$2.9M
The placenta: a novel target of sex specific neurotoxicity by fire retardantsR01ES028110 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI MEITZEN, JOHN · 2017 to 2022
$2.4M
NIEHS NIH HHS P30 ES025128NIEHS NIH HHS P42 ES027704NIEHS NIH HHS P42 ES031009NIEHS NIH HHS R01 ES028110NIEHS NIH HHS U01 ES026717
6 · The paper itself

Abstract

introductionFlame retardants (FRs) are common bodily and environmental pollutants, creating concern about their potential toxicity. We and others have found that the commercial mixture FireMaster® 550 (FM 550) or its individual brominated (BFR) and organophosphate ester (OPFR) components are potential developmental neurotoxicants. Using Wistar rats, we previously reported that developmental exposure to FM 550 or its component classes produced sex- and compound-specific effects on adult socioemotional behaviors. The underlying mechanisms driving the behavioral phenotypes are unknown.

methodsTo further mechanistic understanding, here we conducted transcriptomics in parallel with a novel lipidomics approach using cortical tissues from newborn siblings of the rats in the published behavioral study. Inclusion of lipid composition is significant because it is rarely examined in developmental neurotoxicity studies. Pups were gestationally exposed via oral dosing to the dam to FM 550 or the BFR or OPFR components at environmentally relevant doses.

resultsThe neonatal cortex was highly sexually dimorphic in lipid and transcriptome composition, and males were more significantly impacted by FR exposure. Multiple adverse modes of action for the BFRs and OPFRs on neurodevelopment were identified, with the OPFRs being more disruptive than the BFRs via multiple mechanisms including dysregulation of mitochondrial function and disruption of cholinergic and glutamatergic systems. Disrupted mitochondrial function by environmental factors has been linked to a higher risk of autism spectrum disorders and neurodegenerative disorders. Impacted lipid classes included ceramides, sphingomyelins, and triacylglycerides. Robust ceramide upregulation in the OPFR females could suggest a heightened risk of brain metabolic disease.

conclusionsThis study reveals multiple mechanisms by which the components of a common FR mixture are developmentally neurotoxic and that the OPFRs may be the compounds of greatest concern.

Indexed as

Flame RetardantsPolybrominated BiphenylsAnimalsFemaleLipidsMaleOrganophosphatesRatsRats, WistarFiremaster 550Flame RetardantsLipidsOrganophosphatesPolybrominated BiphenylsBrainCholineDevelopmental neurotoxicityDNTEnvironmental toxicologyFlame retardantsITPs IPPLipidomicsTPHPTPPTranscriptomics

Identifiers

PMID36075192
PMCPMC9992460
OpenAlexW4294970284

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.