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Cited by 10Toxic Organic Pollutants ImpactEffects and risks of endocrine disrupting chemicalsPer- and polyfluoroalkyl substances research

Mechanisms of flame retardant toxicity and their impacts on anxiety and cognition in the brain

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Rojas, Catherine M, Wiersielis, Kimberly R, Roepke, Troy A·2025·Endocrinology
DOI 10.1210/endocr/bqaf074PMC PMC12053249
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Abstract

Flame retardants have been used extensively to reduce flammability in household and industrial materials raising significant concerns due to their toxicological effects, particularly on neurodevelopment and cognition. These chemicals, including legacy compounds such as polybrominated diphenyl ethers and newer organophosphate flame retardant, exhibit endocrine-disrupting properties that interfere with hormonal pathways, neurotransmission, and synaptic plasticity. Epidemiological studies have linked flame retardant exposure to adverse developmental outcomes, including anxiety and cognitive deficits. Mechanistic research reveals that flame retardants disrupt neurogenesis, synaptogenesis, and neurotransmitter pathways, often mediated through oxidative stress, mitochondrial dysfunction, and nuclear receptor modulation. Animal studies corroborate these findings, showing impaired spatial memory, altered anxiety-like behaviors, and disrupted neurochemical homeostasis following perinatal and postnatal exposure to flame retardants. Emerging organophosphate flame retardants, such as bis(2-ethylhexyl) phenyl phosphate, demonstrate comparable or increased toxicity, further emphasizing the need for regulatory scrutiny and safer alternatives. This review synthesizes current knowledge on the neurotoxic mechanisms of flame retardants, highlighting their impact on anxiety and cognition across developmental stages. Understanding these pathways is essential to mitigating the long-term environmental and human health effects of flame retardant exposure.

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  • PBDEs are persistent and lipophilic, and due to regulatory restrictions are increasingly replaced by OPFRs, which are not harmless.

    “Among the most prominent representatives are polybrominated diphenyl ethers (PBDEs), which are characterized by their persistence and lipophilic nature. Due to regulatory restrictions, PBDEs are increasingly being replaced by organophosphate flame retardants (OPFRs), which are by no means harmless (Damiano et al., 2025; Dsouki et al., 2024; Rojas et al., 2025).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Rojas et al., 2025

    The Abstract (page unavailable) says most PBDEs have been phased out since 2009, exposure persists, and emerging OPFRs raise concern as potentially harmful substitutions. It does not state that PBDEs are lipophilic or specifically attribute their replacement to regulatory restrictions; nor does it establish that OPFR use is increasingly replacing PBDE use. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Phosphate-based FRs downregulate synaptic structural proteins such as PSD-95 and impair spatial learning in the Morris Water Maze.

    “Phosphate-based FRs, which downregulate synaptic structural proteins such as PSD-95, impair spatial learning in the Morris Water Maze, a classic test of hippocampus-dependent plasticity (Rojas et al., 2025).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Rojas et al., 2025

    The Mechanisms of Toxicity passage (indexed as Abstract; page unavailable) reports that triphenyl phosphate, an organophosphate flame retardant, reduced hippocampal PSD-95. It attributes Morris Water Maze impairment to mice exposed to brominated flame retardants, not triphenyl phosphate; the phosphate-exposure learning deficits it describes were measured with Y-maze and Novel Object Recognition tests. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Flame retardants are a heterogeneous group of synthetic chemicals used to reduce flammability, and they accumulate in the environment and are detectable in organisms.

    “FRs are a very heterogeneous group of synthetic chemicals used in a wide range of industrial and household products to reduce flammability (Rojas et al., 2025). These substances are particularly relevant because they accumulate in the environment and are detectable in organisms.”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Rojas et al., 2025

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Cited by

Sorted by citations

Authors
Rojas, C. M., Wiersielis, K. R., & Roepke, T. A.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Roepke, Troy A
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2025-04-15
Volume
166
Issue
6
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endocr/bqaf074
PMC
PMC12053249
OpenAlex
W4409418194
Cited by
10
References
2
Citations by year
2026: 8 · 2025: 2
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • National Institutes of Health (R01MH123544, P30ES005022)
  • National Institute of Environmental Health Sciences (T32ES007148, K99ES033256)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
Keywords
flame retardants, neurotoxicity, anxiety, cognitive impairment, polybrominated diphenyl ethers, organophosphate flame retardants, endocrine disruption, brain development, oxidative stress, mitochondrial dysfunction, neurotransmission, synaptic plasticity, spatial memory, perinatal exposure, postnatal exposure, neurogenesis, synaptogenesis
MeSH terms
Animals, Anxiety, Brain, Cognition, Flame Retardants, Humans, Endocrine Disruptors, Halogenated Diphenyl Ethers

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