ReviewIs decabromodiphenyl ether (BDE-209) a developmental neurotoxicant?
Introduction
Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants consisting of 209 congeners, which have been commercialized as penta-, octa-, and deca-brominated mixtures (Alaee et al., 2003). PentaBDE and octaBDE mixtures are no longer produced and commercialized in the European Union and the United States, though they are still used in other parts of the world. In contrast, decaBDE continues to be widely used, though some European countries (e.g. Norway) or states in the U.S.A. (e.g. Maine) have recently banned their use. The manufacturers have agreed to discontinue production of decaBDE in the U.S.A. as of 2013 (USEPA, 2010). PBDEs are additive flame retardants, i.e. they are not bound to the polymer like other flame retardants, and can leach from the products and find their way into the environment. In the past decade, PBDEs have become widespread environmental pollutants, having been detected in outdoor and indoor air, dust, sediments, soil, sludge, birds, fish, marine mammals and other mammals (deWit, 2002, Hites et al., 2004, Law et al., 2006, Chen and Hale, 2010, USEPA, 2010). Exposure of humans has also been documented by several studies (Gill et al., 2004, McDonald, 2005). Exposure occurs primarily through dust and through the diet. Body burden is higher, by at least an order of magnitude, in the U.S. population compared to Japan and the E.U. (Thomsen et al., 2002, Schecter et al., 2005a, Lorber, 2007, USEPA, 2010), though more recent data indicate high levels of exposures in fast developing nations such as India and China (J. Wang et al., 2010a). The highest body burden is found in infants and children, because of exposure through breast milk and household dust (Furst, 2006, Schecter et al., 2003, Fischer et al., 2006, Harrad et al., 2008a), and in occupationally exposed workers (Sjodin et al., 1999, Qu et al., 2007). PBDEs have also been found to cross the placenta, and levels in cord blood are comparable to those found in the mothers (Gomara et al., 2007). A recent document, the “San Antonio statement of brominated and chlorinated flame retardants”, voices concern for the widespread contamination of these compounds, including PBDEs (DiGangi et al., 2010).
Section snippets
Developmental neurotoxicity of tetra-, penta-, and hexa-BDEs
The high body burden during early development has raised concerns about possible developmental toxicity and neurotoxicity of PBDEs. Several studies have indicated that PBDEs cause developmental neurotoxicity, and recent reviews have summarized the findings of animal and in vitro studies (Branchi et al., 2003, Birnbaum and Staskal, 2004, McDonald, 2005, Costa and Giordano, 2007, Costa et al., 2008, Williams and DeSesso, 2010). In vivo exposure to various PBDEs [BDE-47, BDE-99, BDE-153, DE-71 (a
General toxicology of BDE-209
BDE-209 (3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether) is a fully brominated PBDE. It is sold as a decaBDE mixture which contains primarily (>97%) BDE-209, minor amounts of nonaBDEs (BDE-206, BDE-207, BDE-208), and traces of octaBDEs (Goodman, 2009). Among all PBDEs, BDE-209 has the most extensive toxicological database. Standard toxicology studies (e.g. acute, sub-chronic, chronic, reproductive/developmental toxicity) are available, as well as a carcinogenicity study. These studies have been
Animal studies
There are only a limited number of published studies investigating the developmental neurotoxicity of BDE-209, and a summary is given in Table 1. A first series of studies was carried out at Uppsala University in Sweden by Viberg, Eriksson, and their colleagues (Viberg et al., 2003a, Viberg et al., 2007, Viberg et al., 2008, Johansson et al., 2008, Viberg, 2009a), and these have been critically discussed in some recent publications (Goodman, 2009, Hardy et al., 2009). The same paradigm of
Occurrence and body burden of BDE-209
The analysis of BDE-209 is considered a challenging task, due to its high molecular weight, its peculiar chromatographic characteristics, its thermolability and photosensitivity, and the possibility of contamination from flame-retarded electronic equipment (Thuresson et al., 2005). Thus, it is not surprising that much less information exists on levels of BDE-209 in environmental media, biota and humans, compared to other lower-brominated PBDEs. Furthermore, the indicated issues may lead to
Derivation of an RfD for BDE-209
Over the years, various agencies and organizations have proposed reference doses (RfD) for BDE-209 (Table 5). The National Research Council of the National Academy of Sciences (NAS, 2000) based its RfD of 4.0 mg/kg/day on the chronic National Toxicology Program (NTP) study (NTP, 1986), by applying a 300× uncertainty factor (UF; 10× for interspecies differences, 10× for intraspecies differences, 3× for database deficiencies) to the NOAEL (no-observed adverse effect level) of 1120 mg/kg/day for
Conclusions and research needs
As other flame retardants, PBDEs have contributed to a significant reduction of mortality, morbidity, and property damage due to fires in the past several decades. Yet, their propensity to leach from the products and to become widespread environmental pollutants, have raised concerns in recent years (DiGangi et al., 2010). This has led to the ban of penta- and octa-BDEs in several countries, and restrictions on decaBDE (BDE-209) in others. One of the driving arguments for concern on PBDEs has
Conflict of interest statement
The authors declare that they have no conflicts of interest.
Acknowledgment
Research by the authors has been supported in part by a grant from NIEHS (P30ES07033).
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