Journal
NEUROTOXICOLOGY
Volume 32, Issue 1, Pages 9-24Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.neuro.2010.12.010
Keywords
Polybrominated diphenyl ethers; DecaBDE; BDE-209; Developmental neurotoxicity; Reference dose
Categories
Funding
- NIEHS [P30ES07033]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES007033] Funding Source: NIH RePORTER
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Polybrominated diphenyl ether (PBDE) flame retardants have become ubiquitous environmental pollutants. The relatively higher body burden in toddlers and children has raised 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 USA 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. (C) 2010 Elsevier Inc. All rights reserved.
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