Effects of neonatal exposure to the flame retardant tetrabromobisphenol-A, aluminum diethylphosphinate or zinc stannate on long-term potentiation and synaptic protein levels in mice
Open accessAbstract
Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.
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In neonatal mice, TBBPA caused a small reduction in post-tetanic potentiation, while overall LTP effects remained modest, indicating that brief developmental exposure can perturb early activity-dependent synaptic strengthening.
“In neonatal mice, TBBPA caused a small reduction in post-tetanic potentiation, although overall LTP effects remained modest, indicating that even brief developmental exposure can perturb early forms of activity-dependent synaptic strengthening (Dingemans et al., 2007; Hendriks et al., 2015).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Hendriks et al., 2015
The Basal excitability and synaptic transmission section reports slightly lower post-tetanic potentiation after neonatal TBBPA exposure, but the difference from controls was not statistically significant. The Discussion likewise describes the LTP changes as minor and insignificant. The claim captures the direction and modest size of the observed changes, but its assertion that exposure perturbs synaptic strengthening is stronger than these results establish. (LLM, conf=0.84)
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“In neonatal mice, TBBPA caused a small reduction in post-tetanic potentiation, although overall LTP effects remained modest, indicating that even brief developmental exposure can perturb early forms of activity-dependent synaptic strengthening (Dingemans et al., 2007; Hendriks et al., 2015).”
- Authors
- Hendriks, H. S., Koolen, L. A. E., Dingemans, M. M. L., Viberg, H., Lee, I., Leonards, P. E. G., Ramakers, G. M. J., & Westerink, R. H. S.
- Affiliations
- Utrecht University (NL)
- Uppsala University (SE)
- Vrije Universiteit Amsterdam (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Westerink, Remco H. S.
- ORCID
- Venue
- Archives of Toxicology
- Published
- 2014-09-25
- Volume
- 89
- Issue
- 12
- Pages
- 2345-2354
- ISSN
- 0340-5761 (ISSN-L)
- 1432-0738
- OpenAlex
- W1969464092
- Cited by
- 15
- References
- 45
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Archives of Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- European Commission (FP7-ENV-2008, FP7-ENV-2008-1, 226563)
- Universiteit Utrecht
- Uppsala Universitet
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Materials Science › Polymers and Plastics › Flame retardant materials and properties
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- tetrabromobisphenol A, aluminum diethylphosphinate, Zn2SnO4, halogen-free flame retardants, neonatal exposure, developmental neurotoxicity, long-term potentiation, synaptic plasticity, hippocampus, post-tetanic potentiation, synaptic proteins, bioavailability, brominated flame retardants
- MeSH terms
- Age Factors, Aluminum, Animals, Animals, Newborn, Biological Availability, Flame Retardants, Hippocampus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuronal Plasticity, Organophosphorus Compounds, Polybrominated Biphenyls, Tissue Distribution, Long-Term Potentiation, Tin Compounds, Neurotoxicity Syndromes, Mice
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