title: 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.
abstract: 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.
authors.affiliation: Neurotoxicology Research Group, Toxicology Division, Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, 3508 TD, Utrecht, The Netherlands.
authors.forename: Hester S
authors.initials: HS
authors.lastname: Hendriks
authors.affiliation: Master's Programme in Neuroscience and Cognition, Utrecht University, 3508 TC, Utrecht, The Netherlands.
authors.forename: Lucas A E
authors.initials: LA
authors.lastname: Koolen
authors.affiliation: Neurotoxicology Research Group, Toxicology Division, Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, 3508 TD, Utrecht, The Netherlands.
authors.forename: Milou M L
authors.initials: MM
authors.lastname: Dingemans
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Viberg
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
authors.forename: Iwa
authors.initials: I
authors.lastname: Lee
authors.affiliation: Institute for Environmental Studies (IVM), VU University, Amsterdam, The Netherlands.
authors.forename: Pim E G
authors.initials: PE
authors.lastname: Leonards
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Geert M J
authors.initials: GM
authors.lastname: Ramakers
authors.affiliation: Neurotoxicology Research Group, Toxicology Division, Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, 3508 TD, Utrecht, The Netherlands. r.westerink@uu.nl.
authors.forename: Remco H S
authors.initials: RH
authors.lastname: Westerink
mesh_terms: D000367:Age Factors; D000535:Aluminum / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001682:Biological Availability; D005411:Flame Retardants / Q000493:pharmacokinetics / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000633:toxicity; D011075:Polybrominated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity; D017971:Tin Compounds / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D005411:Flame Retardants; D009419:Nerve Tissue Proteins; D009943:Organophosphorus Compounds; D011075:Polybrominated Biphenyls; D017971:Tin Compounds; D000535:Aluminum; C020806:tetrabromobisphenol A
keywords: Aluminum diethylphosphinate (Alpi); Developmental neurotoxicity; Flame retardants; Hippocampal synaptic plasticity; Tetrabromobisphenol-A (TBBPA); Zinc stannate (ZS)