Is decabromodiphenyl ether (BDE-209) a developmental neurotoxicant?

Abstract

Polybrominated diphenyl ether (PBDE) flame retardants have become ubiquitous environmental pollutants. The relatively higher body burden in toddlers and children has reaised concern for their potential developmental neurotoxicity, which has been suggested by animal studies, in vitro experiments, and recent human epidemiological evidence. While lower brominated PBDEs have been banned in several countries, the fully brominated decaBDE (BDE-209) is still utilized, though manufacturers will discontinue production in the U.S.A. in 2013. The recent decision by the U.S. Environmental Protection Agency to base the Reference Dose (RfD) for BDE-209 on a developmental neurotoxicity study has generated some controversy. Because of its bulky configuration, BDE-209 is poorly absorbed and does not easily penetrate the cell wall. Its acute and chronic toxicities are relatively low, with the liver and the thyroid as the primary targets, though there is some evidence of carcinogenicity. A few animal studies have indicated that BDE-209 may cause developmental neurotoxicity, affecting motor and cognitive domains, as seen for other PBDEs. Limited in vivo and in vitro studies have also evidenced effects of BDE-209 on thyroid hormone homeostasis and direct effects on nervous cells, again similar to what found with other lower brominated PBDEs. In contrast, a recent developmental neurotoxicity study, carried out according to international guidelines, has provided no evidence of adverse effects on neurodevelopment, and this should be considered in a future re-evaluation of BDE-209. While estimated exposure to BDE-209 in children is believed to be several orders of magnitude below the most conservative RfD proposed by the USEPA, questions remain on the extent and relevance of BDE-209 metabolism to lower brominated PBDEs in the environment and in humans.

Effect of combined exposure to lead and decabromodiphenyl ether on neurodevelopment of zebrafish larvae

“…The toxic effects of BDE-209 mainly consist of thyroid disruption and neurotoxicity (Costa and Giordano, 2011). For example, some studies report developmental neurotoxicity associated with BDE-209 exposure, including impairment of locomotor activity and cognition (Viberg et al, 2003).…”

“…Exposure to BDE-209 alters the expression of genes and proteins involved in synapse and axon formation, neuronal morphology, cell migration, and synaptic plasticity (Viberg et al, 2008;Dingemans et al, 2011). In addition, BDE-209 has been shown to cause oxidative stress in neurons, which leads to apoptotic neuronal death (Chen et al, 2010;Costa and Giordano, 2011).…”

BDE-209 in the Australian Environment: Desktop review

“…As summarised and detailed in Costa and Giordiano (47), animal studies report BDE-209 may cause developmental neurotoxicity, affecting motor and cognitive domains, as seen for other PBDEs, including BDE-47 and BDE-99. Its acute and chronic toxicities are relatively low, with the liver and the thyroid as the primary targets, though there is some evidence of carcinogenicity (47). Limited in vivo and in vitro studies have also evidenced effects of BDE-209 on thyroid hormone homeostasis and direct effects on nervous system cells (47).…”

Bioconcentration and metabolism of BDE-209 in the presence of titanium dioxide nanoparticles and impact on the thyroid endocrine system and neuronal development in zebrafish larvae

“…Among polybrominated diphenyl ethers (PBDEs), deca-BDEs (BDE-209) have been the most widely used congener in brominated flame retardants (Costa & Giordano, 2011;Noyes et al, 2011). Although they are no longer produced and commercialized within the European Union, and USA voluntarily ceased BDE-209 production in 2013 (Costa & Giordano, 2011;USEPA, 2010), exposures and global contamination continue due to their widespread use in other countries, especially in Asia, where products that contain BDE-209 are readily used, recycled and discarded Guan et al, 2007).…”

“…Although they are no longer produced and commercialized within the European Union, and USA voluntarily ceased BDE-209 production in 2013 (Costa & Giordano, 2011;USEPA, 2010), exposures and global contamination continue due to their widespread use in other countries, especially in Asia, where products that contain BDE-209 are readily used, recycled and discarded Guan et al, 2007). Moreover, BDE-209 from electronic waste (e-waste) has emerged as the major congener detected in the environment, human and wildlife samples from e-waste recycling sites and has become an increasing environmental problem in China (Bi et al, 2007;Chen et al, 2009;Zhang et al, 2011).…”