Developmental neurotoxicity of polybrominated diphenyl ether (PBDE) flame retardants

Abstract

Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants used in a variety of consumer products. In the past 25 years, PBDEs have become ubiquitous environmental contaminants. They have been detected in soil, air, sediments, birds, marine species, fish, house dust, and human tissues, blood and breast milk. Diet and house dust appear to be the major sources of PBDE exposure in the general population, though occupational exposure can also occur. Levels of PBDEs in human tissues are particularly high in North America, compared to Asian and European countries, and have been increasing in the past 30 years. Concentrations of PBDEs are particularly high in breast milk, resulting in high exposure of infants. In addition, for toddlers, dust has been estimated to account for a large percentage of exposure. PBDEs can also cross the placenta, as they have been detected in fetal blood and liver. Tetra-, penta- and hexaBDEs are most commonly present in human tissues. The current greatest concern for potential adverse effects of PBDEs relates to their developmental neurotoxicity. Pre- or postnatal exposure of mice or rats to various PBDEs has been shown to cause long-lasting changes in spontaneous motor activity, mostly characterized as hyperactivity or decreased habituation, and to disrupt performance in learning and memory tests. While a reduction in circulating thyroid hormone (T(4)) may contribute to the developmental neurotoxicity of PBDEs, direct effects on the developing brain have also been reported. Among these, PBDEs have been shown to affect signal transduction pathways and to cause oxidative stress. Levels of PBDEs causing developmental neurotoxicity in animals are not much dissimilar from levels found in highly exposed infants and toddlers.

Fig. 1

General chemical structure of PBDEs (x + y = 1 to 10).

Fig. 2

Serum levels (ng/g lipid) of polychlorinated dibenzodioxins (PCDD), polychlorinated dibenzo furans (PCDF), co-planar polychlorinated biphenyls (PCB), mono-ortho substitutes PCBs, and PBDEs in the U.S. population in 1973 and 2003. Data from Schecter et al. (2005).

Fig. 3

Spontaneous behavior in 4 month-old NMRI mice exposed to a single oral dose of BDE-47, BDE-99 and TBBPA (tetrabromo-bis-phenol A) on PND 10. From Eriksson et al. (2001) with permission.