title: Modulation of human α4β2 nicotinic acetylcholine receptors by brominated and halogen-free flame retardants as a measure for in vitro neurotoxicity.
abstract: Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concern associated with BFRs argues for replacement by safer alternatives. However, the (neuro)toxic potential of alternative halogen-free flame retardants (HFFRs) is unknown. Previous research identified the nervous system as a sensitive target organ for BFRs, with modulation of excitatory nicotinic acetylcholine (nACh) receptors as one of the modes of action. Since it is essential to assess the (neuro)toxic potential of HFFRs before large scale use, we measured the effects of three BFRs and 13 HFFRs on the function of human α(4)β(2) nACh receptors, expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique. The results demonstrate that some BFRs (TBBPA and to a lesser extent BDE-209) and HFFRs (TPP, Alpi, APP, MMT and to a lesser extent ATH, ATO, MHO, MPP, RDP and ZHS) act as nACh receptor antagonists. Contrary, BPS, BDP, DOPO and ZS were unable to modulate nACh receptors. Despite the lack of toxicological data on HFFRs and the need for additional studies to perform a full (neuro)toxic risk assessment, the current data on antagonistic effects on nACh receptors could be an important step in prioritizing viable HFFRs for substitution of BFRs.
authors: Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL-3508 TD Utrecht, The Netherlands.
authors: Hester S
authors: HS
authors: Hendriks
authors: Regina G D M
authors: RG
authors: van Kleef
authors: Remco H S
authors: RH
authors: Westerink
mesh_terms: D000818:Animals; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009865:Oocytes / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014981:Xenopus
chemical_list: D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D009498:Neurotoxins; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2