Lema Sean C, Schultz Irvin R, Scholz Nathaniel L, Incardona John P, Swanson Penny
NOAA Fisheries, Northwest Fisheries Science Center, 2725 Montlake Boulevard East, Seattle, WA 98112, USA.
Aquat Toxicol. 2007 May 31;82(4):296-307. doi: 10.1016/j.aquatox.2007.03.002. Epub 2007 Mar 7.
Polybrominated diphenyl ethers (PBDEs) are added to plastics, polyurethane foam, and textiles as a flame retardant. While PBDEs play a key role in reducing loss of human life and property from fires, these flame retardants have become pervasive organic contaminants in the environment and in the tissues of fish, birds, marine mammals, and humans. Levels of PBDEs in wildlife and humans continue to rise, raising concerns about potential ecological and health risks associated with exposure to these chemicals. Nevertheless, there is little currently known about the toxicological effects of PBDE exposure. Here, we examined the developmental toxicity of the PBDE congener 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) using the zebrafish (Danio rerio) as an ontogenetic model. Zebrafish embryos were exposed continuously to dissolved phase PBDE 47 (100-5000 microg/l) beginning 3-5 h post-fertilization (hpf). Fish treated with the highest concentrations of PBDE 47 delayed hatching, had reduced growth post-hatching, and displayed an abnormal dorsal curvature of the body with flexion at the hindbrain. By 96h post-fertilization larvae exposed to PBDE 47 had significant tachycardia, which progressed into atrioventricular block arrhythmias. Microinjection of fluorescent dye into the hindbrain ventricle revealed that cerebrospinal fluid in the neural tube and brain ventricles flowed more slowly in fish larvae exposed to PBDE 47, a likely etiology for the dorsal curvature. Similar, though much less pronounced, developmental toxicity also occurred in larvae exposed to PBDE 47 only for a 20h period during early embryogenesis (3-23 hpf), suggesting that PBDEs incorporated in lipid of the egg are bioavailable and cause toxicity later in life. Taken together, this work indicates that exposure to PBDE 47 can cause morphological abnormalities, impair cardiovascular function and cerebrospinal fluid flow, and provides a tractable starting point for using the zebrafish model to explore molecular mechanisms of PBDE toxicity.
多溴二苯醚（PBDEs）作为一种阻燃剂被添加到塑料、聚氨酯泡沫和纺织品中。虽然多溴二苯醚在减少火灾造成的人员生命和财产损失方面发挥着关键作用，但这些阻燃剂已成为环境以及鱼类、鸟类、海洋哺乳动物和人类组织中普遍存在的有机污染物。野生动物和人类体内的多溴二苯醚水平持续上升，这引发了人们对接触这些化学物质可能带来的生态和健康风险的担忧。然而，目前对于多溴二苯醚暴露的毒理学影响知之甚少。在此，我们以斑马鱼（Danio rerio）作为个体发育模型，研究了多溴二苯醚同系物2,2',4,4'-四溴二苯醚（PBDE 47）的发育毒性。斑马鱼胚胎在受精后3 - 5小时（hpf）开始连续暴露于溶解态的PBDE 47（100 - 5000微克/升）。用最高浓度PBDE 47处理的鱼孵化延迟，孵化后生长减缓，并表现出身体背部异常弯曲，后脑处有屈曲。到受精后96小时，暴露于PBDE 47的幼虫出现明显的心动过速，并发展为房室传导阻滞性心律失常。向后脑室微量注射荧光染料显示，暴露于PBDE 47的鱼幼虫神经管和脑室中的脑脊液流动更缓慢，这可能是背部弯曲的病因。类似的发育毒性也出现在仅在胚胎早期（3 - 23 hpf）暴露于PBDE 47 20小时的幼虫中，不过程度较轻，这表明卵脂质中所含的多溴二苯醚具有生物可利用性，并在后期导致毒性。综上所述，这项研究表明，暴露于PBDE 47会导致形态异常、损害心血管功能和脑脊液流动，并为利用斑马鱼模型探索多溴二苯醚毒性的分子机制提供了一个易于处理的起点。
