Especially, the use of FR in baby products and the exposure to children are of concern as the developing brain is much more vulnerable to environmental perturbation than the brain of adults (O'Rahilly and Muller 2008 Smirnova et al. 2017 Grandjean and Landrigan 2014 Mie et al. This is of concern, as OPFRs bear some structural similarities to organophosphate pesticides that are well known to induce (developmental) neurotoxicity (Burke et al. Hence, it is likely that the manufacturers will explore the potential for use of OPFRs in televisions and other electronics as alternative methods to meet flammability codes.Īlthough there has been an increase in the use of OPFRs, there is still relatively limited information on their potential health effects. The use of OPFRs is further anticipated to increase following the recent proposal by the European Commission to prohibit the class of organohalogen chemicals in electronic display enclosures and stands effective since April 2021 (Commission 2018). Following the phase out of PBDEs, there is increasing evidence showing higher exposure to OPFRs compared to PBDEs from hand wipes in toddlers, and house dust suggesting that the magnitude of exposure via hand-to-mouth and dermal transfer pathways is potentially greater for OPFRs than for PBDEs (Blum et al. 2013), and mainly been replaced by organophosphorus FR (OPFR) (Blum et al. 2002).ĭue to these human health concerns, PBDEs have been banned in Europe and phased out in the USA (Birnbaum and Staskal 2004 Feo et al. In particular, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-the most abundant PBDE congener in the environment and human serum (Birnbaum and Staskal 2004 EPA US 2008)-has been shown to affect the adult and developing nervous system (Dingemans et al. However, the halogenated FR have been linked to the development of cancer, endocrine disruption, immunotoxicity, reproductive toxicity, and fetal and child development perturbation (Birnbaum and Staskal 2004 Costa and Giordano 2007 Roze et al. Prior to 2005, halogenated polybrominated diphenyl ethers (PBDEs) were the primary FR used in the USA. However, FR exhibit characteristics similar to environmental toxicants, such as heavy metals, air pollutants and pesticides that are well recognized as hazardous to human health and inducers of neurodevelopmental damage. The global FR consumption has surpassed 2 million tons and is yet expected to increase due to international flammability standards (Ceresana 2018). Taken together, this appears to be a case of regretful substitution with substances not less developmentally neurotoxic in a primary rat 3D model.įlame retardants (FR) are a group of compounds, which are added to consumer products, including upholstered furniture, electrical devices, baby products, textiles and plastics, to restrain or delay flame propagation to prevent fire spreading (Dishaw et al. Pathway/category overrepresentation shows disruption in 1) transmission of action potentials, cell–cell signaling, synaptic transmission, receptor signaling, (2) immune response, inflammation, defense response, (3) cell cycle and (4) lipids metabolism and transportation. An increase of cytokine gene and receptor expressions suggests that exposure to OPFR may induce an inflammatory response. At the 5 µM concentrations, the OPFR more than BDE-47 interfered with myelination. Several findings suggest astrogliosis induced by the OPFR, but not BDE-47. At similar concentrations, the FR currently in use decreased plasma membrane dopamine active transporter expression, while BDE-47 did not. Furthermore, n-acetyl aspartate (NAA), considered a neurologic diagnostic molecule, was decreased by all OPFR. This includes toxicity to neurons in the low µM range all FR decrease the neurotransmitters glutamate and GABA (except BDE-47 and TPHP). Employing mass spectroscopy-based metabolomics and transcriptomics, we observe at similar human-relevant non-cytotoxic concentrations (0.1–5 µM) stronger developmental neurotoxic effects by OPFR. Leveraging a 3D rat primary neural organotypic in vitro model (rat brainsphere), we compare developmental neurotoxic effects of BDE-47-the most abundant PBDE congener-with four OPFR (isopropylated phenyl phosphate-IPP, triphenyl phosphate-TPHP, isodecyl diphenyl phosphate-IDDP, and tricresyl phosphate (also known as trimethyl phenyl phosphate)-TMPP). Due to regulatory bans and voluntary substitutions, halogenated polybrominated diphenyl ether (PBDE) flame retardants (FR) are increasingly substituted by mainly organophosphorus FR (OPFR).
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