Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA.
Neurotoxicology. 2011 Jan;32(1):9-24. doi: 10.1016/j.neuro.2010.12.010. Epub 2010 Dec 21.
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 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.
多溴二苯醚（PBDE）阻燃剂已成为无处不在的环境污染物。由于在幼儿和儿童体内的蓄积量相对较高，人们对其潜在的发育神经毒性表示担忧，动物研究、体外实验和最近的人类流行病学证据都表明了这一点。虽然一些国家已经禁止使用低溴化的 PBDE，但完全溴化的十溴二苯醚（BDE-209）仍在使用，尽管美国的制造商将在 2013 年停止生产。美国环保署最近决定根据发育神经毒性研究来确定 BDE-209 的参考剂量（RfD），这引起了一些争议。由于其庞大的结构，BDE-209 不易被吸收，也不易穿透细胞壁。它的急性和慢性毒性相对较低，主要靶器官为肝脏和甲状腺，尽管有一些致癌的证据。一些动物研究表明，BDE-209 可能会导致发育神经毒性，影响运动和认知领域，这与其他 PBDE 相似。有限的体内和体外研究也表明 BDE-209 对甲状腺激素稳态和对神经细胞的直接影响，这与其他低溴化 PBDE 类似。相比之下，最近一项按照国际指南进行的发育神经毒性研究并未发现 BDE-209 对神经发育有不良影响，这应该在未来对 BDE-209 的重新评估中加以考虑。虽然儿童接触 BDE-209 的估计水平被认为比美国环保署提出的最保守的 RfD 低几个数量级，但 BDE-209 在环境和人体内向低溴化 PBDE 代谢的程度和相关性仍存在疑问。
