Neurotoxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US EPA, Research Triangle Park, North Carolina 27711, USA.
Toxicol Sci. 2010 Jul;116(1):297-312. doi: 10.1093/toxsci/kfq105. Epub 2010 Apr 7.
Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.7, 10.2, or 30.6 mg/kg/day DE-71 in corn oil by oral gavage from gestational day 6 to weaning. DE-71 did not alter maternal or male offspring body weights. However, female offspring were smaller compared with controls from postnatal days (PNDs) 35-60. Although several neurobehavioral endpoints were assessed, the only statistically significant behavioral finding was a dose-by-age interaction in the number of rears in an open-field test. Developmental exposure to DE-71 caused severe hypothyroxinemia in the dams and early postnatal offspring. DE-71 also affected anogenital distance and preputial separation in male pups. Body weight gain over time, reproductive tissue weights, and serum testosterone concentrations at PND 60 were not altered. Mammary gland development of female offspring was significantly affected at PND 21. Congener-specific analysis of PBDEs indicated accumulation in all tissues examined. Highest PBDE concentrations were found in fat including milk, whereas blood had the lowest concentrations on a wet weight basis. PBDE concentrations were comparable among various brain regions. Thus, perinatal exposure to DE-71 leads to accumulation of PBDE congeners in various tissues crossing blood-placenta and blood-brain barriers, causing subtle changes in some parameters of neurobehavior and dramatic changes in circulating thyroid hormone levels, as well as changes in both male and female reproductive endpoints. Some of these effects are similar to those seen with PCBs, and the persistence of these changes requires further investigation.
多溴联苯醚 (PBDEs) 因其结构与多氯联苯 (PCBs) 相似而被怀疑具有发育毒性。本研究评估了围产期经口给予广泛使用的五溴商业化混合物 DE-71 的大鼠仔鼠的神经行为、激素和生殖效应。妊娠长耳大白鼠从妊娠第 6 天至断奶,每天以玉米油经口灌胃给予 0、1.7、10.2 或 30.6mg/kg DE-71。DE-71 未改变母体或雄性仔鼠体重。然而,与对照组相比,雌性仔鼠从出生后第 35 天至 60 天体重较小。尽管评估了几个神经行为终点,但唯一具有统计学意义的行为发现是在旷场试验中的后腿数量上存在剂量-年龄相互作用。DE-71 的发育暴露导致母鼠和新生仔鼠出现严重的甲状腺素血症。DE-71 还影响雄性幼鼠的肛门生殖器距离和包皮分离。随着时间的推移,体重增加、生殖组织重量和 PND60 时的血清睾丸酮浓度没有改变。雌性仔鼠的乳腺发育在 PND21 时受到显著影响。多溴联苯醚的同系物特异性分析表明,在所有检测组织中均有积累。在脂肪(包括乳汁)中发现了最高的 PBDE 浓度,而血液中的浓度以湿重为基础时最低。PBDE 浓度在各种脑区之间相当。因此,围产期接触 DE-71 导致 PBDE 同系物在各种组织中积累,穿过胎盘和血脑屏障,导致神经行为的一些参数发生细微变化,循环甲状腺激素水平发生显著变化,并导致雄性和雌性生殖终点发生变化。其中一些影响与 PCBs 相似,这些变化的持久性需要进一步研究。