Center for Children's Environmental Health, University of California-Davis, One Shields Avenue, Davis, CA 95616, United States.
Neurotoxicol Teratol. 2011 May-Jun;33(3):393-404. doi: 10.1016/j.ntt.2011.02.003. Epub 2011 Feb 18.
Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants that have become pervasive environmental contaminants and may contribute to adverse health outcomes. We evaluated in mice the developmental neurotoxicity of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), one of the most abundant PBDE congeners detected in animal and human tissues. Female C57BL/6J mice were exposed to daily doses of 0, 0.03, 0.1 or 1mg/kg beginning 4 weeks prior to conception, continuing through gestation and lactation, and ending at weaning on postnatal day (PND) 21. Levels of BDE-47 in blood, brain, liver and adipose tissues of dams were markedly increased after 4 weeks of exposure, around the time of mating, and continued to increase through the time of parturition. Blood levels of BDE-47 in the dosed dams were within the range reported in humans. BDE-47 tissue levels in the dams decreased between parturition and weaning, possibly reflecting mobilization during lactation. Brain BDE-47 levels in the offspring at PND 1 approached those of the dams at parturition. Perinatal exposure to BDE-47 resulted in significant dose dependent growth retardation, slower motor performance in several behavioral tests, and mice exposed to 1mg/kg/day BDE-47 showed altered performance in the Morris water maze. There were no differences between groups in the numbers of pyramidal neurons in hippocampus CA1. These results document accumulation of BDE-47 in several organ systems following exposure to low-levels of BDE-47, and provide evidence that such exposure is associated with early behavioral deficits in exposed neonates.
多溴二苯醚（PBDEs）是一种广泛使用的阻燃剂，已成为普遍存在的环境污染物，可能导致不良健康后果。我们在小鼠中评估了 2,2',4,4'-四溴二苯醚（BDE-47）的发育神经毒性，BDE-47 是在动物和人体组织中检测到的最丰富的多溴二苯醚同系物之一。雌性 C57BL/6J 小鼠从受孕前 4 周开始接受每日 0、0.03、0.1 或 1mg/kg 的剂量，持续到妊娠和哺乳期，并在产后第 21 天（PND）断奶结束。在暴露 4 周后，母体血液、大脑、肝脏和脂肪组织中的 BDE-47 水平明显升高，此时正值交配期，并持续升高至分娩时。在接受剂量的母鼠血液中的 BDE-47 水平在人类报道的范围内。在分娩和断奶期间，母体组织中的 BDE-47 水平下降，可能反映了哺乳期的动员。在 PND 1 时，子代大脑中的 BDE-47 水平接近母体分娩时的水平。围产期暴露于 BDE-47 导致明显的剂量依赖性生长迟缓，在几项行为测试中运动表现较慢，并且每天暴露于 1mg/kg BDE-47 的小鼠在 Morris 水迷宫中表现出行为改变。在海马 CA1 中的锥体神经元数量在各组之间没有差异。这些结果证明了在暴露于低水平 BDE-47 后，BDE-47 在几个器官系统中的积累，并提供了证据表明这种暴露与暴露于新生儿的早期行为缺陷有关。
