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Cited by 14Toxic Organic Pollutants ImpactPesticide Exposure and ToxicityEffects and risks of endocrine disrupting chemicals

Developmental exposure to the flame retardant, Triphenyl phosphate, causes long-lasting neurobehavioral and neurochemical dysfunction

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Hawkey, Andrew B., Evans, Janequia, Holloway, Zade R., Pippen, Erica, Jarrett, Olivia, Kenou, Bruny, Slotkin, Theodore A., Seidler, Frederic J. +1 more·2023·Birth Defects Research
DOI 10.1002/bdr2.2125PMC PMC10197196
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Abstract

BACKGROUND: Human exposures to organophosphate flame retardants result from their use as additives in numerous consumer products. These agents are replacements for brominated flame retardants but have not yet faced similar scrutiny for developmental neurotoxicity. We examined a representative organophosphate flame retardant, triphenyl phosphate (TPP) and its potential effects on behavioral development and dopaminergic function. METHODS: ) via subcutaneous osmotic minipumps, begun preconception and continued into the early postnatal period. Offspring were administered a battery of behavioral tests from adolescence into adulthood, and littermates were used to evaluate dopaminergic synaptic function. RESULTS: Offspring with TPP exposures showed increased latency to begin eating in the novelty-suppressed feeding test, impaired object recognition memory, impaired choice accuracy in the visual signal detection test, and sex-selective effects on locomotor activity in adolescence (males) but not adulthood. Male, but not female, offspring showed marked increases in dopamine utilization in the striatum, evidenced by an increase in the ratio of the primary dopamine metabolite (3,4-dihydroxyphenylacetic acid) relative to dopamine levels. CONCLUSIONS: These results indicate that TPP has adverse effects that are similar in some respects to those of organophosphate pesticides, which were restricted because of their developmental neurotoxicity.

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  • Developmental exposure to TPP caused long-lasting neurobehavioral and neurochemical dysfunction, consistent with persistent disruption of dopaminergic and broader monoaminergic signaling.

    “More specifically, developmental exposure to TPP caused long-lasting neurobehavioral and neurochemical dysfunction, consistent with persistent disruption of dopaminergic and broader monoaminergic signaling (Hawkey et al., 2023).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Hawkey et al., 2023

    The Discussion reports neurobehavioral and neurochemical anomalies persisting into adulthood, and the Results > Neurochemistry identify increased striatal dopamine utilization in male offspring. The broader monoaminergic claim is not supported: the reported effects were specific to the striatum, with no corresponding effects in the cortex, where norepinephrine was assessed. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Hawkey, A. B., Evans, J., Holloway, Z. R., Pippen, E., Jarrett, O., Kenou, B., Slotkin, T. A., Seidler, F. J., & Levin, E. D.
Affiliations
Duke University (US)
Corresponding author
Levin, Edward D.
ORCID
Venue
Birth Defects Research
Publisher
Wiley
Published
2022-11-11
Volume
115
Issue
3
Pages
357-370
ISSN
2472-1727 (ISSN-L)
DOI
10.1002/bdr2.2125
PMC
PMC10197196
OpenAlex
W4308834286
Cited by
14
References
0
Citations by year
2026: 9 · 2025: 3 · 2024: 1 · 2023: 1
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Birth Defects Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Environmental Health Sciences
  • Duke University (ES010356)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords
triphenyl phosphate, organophosphate flame retardants, developmental neurotoxicity, prenatal exposure, postnatal exposure, neurobehavioral impairment, dopaminergic activity, dopamine utilization, striatum, DOPAC, novelty-suppressed feeding, object recognition memory, locomotor activity, sex differences, organophosphorus pesticides
MeSH terms
Animals, Dopamine, Flame Retardants, Humans, Male, Organophosphates, Zebrafish, Rats, Sprague-Dawley, Rats

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