Modulation of human α4β2 nicotinic acetylcholine receptors by brominated and halogen-free flame retardants as a measure for in vitro neurotoxicity

    Research output: Contribution to journalArticleAcademicpeer-review

    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.
    Original languageEnglish
    Pages (from-to)266-274
    Number of pages9
    JournalToxicology Letters
    Volume213
    Issue number2
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    Dive into the research topics of 'Modulation of human α4β2 nicotinic acetylcholine receptors by brominated and halogen-free flame retardants as a measure for in vitro neurotoxicity'. Together they form a unique fingerprint.

    Cite this