Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47
Plasma PBDE and thyroxine levels in rats exposed to Bromkal or BDE-47
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DOI：
10.1016/j.chemosphere.2006.05.133
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发表时间：
2007-04-01
期刊：
影响因子：
8.8
通讯作者：
Hallgren, Sara
中科院分区：
文献类型：
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作者：
Darnerud, Per Ola;Aune, Marie;Hallgren, Sara
在实验模型中，多溴二苯醚 (PBDE)（一组溴化阻燃剂）对许多生物终点产生影响，包括神经行为影响、甲状腺和类固醇激素稳态紊乱以及其他类固醇相关影响。几乎完全只研究了与观察到的效应相关的外部剂量指标（基于体重的剂量）。在这项研究中，我们报告了对暴露啮齿类动物甲状腺激素 (TH) 早期研究剩余样本中血浆 PBDE 水平的新分析。雌性 7 周龄 Sprague-Dawley 大鼠每天通过管饲法给予 Bromkal 70-5 DE（研究 1；18 或 36 mg/kg bw/天）或 BDE-47（研究 11；1、6 或 18 mg/kg bw/天），持续两周。两项研究均观察到外部剂量为 18 mg/kg 体重/天时，显着的 TH 效应（血浆游离甲状腺素水平降低），相当于内部（血浆）剂量为 463 μg sumPBDE/g 脂质（研究 I）或 421 μg BDE-47/g 脂质（研究 II）。如果我们比较不同 BDE 同源物对 Bromkal 暴露后大鼠血浆中总 BDE 水平的贡献（研究 II）以及 Bromkal 混合物本身，则在血浆中也发现了 Bromkal 混合物中最重要的同源物。然而，与混合物相比，BDE-99 的相对浓度较低，而 BDE-153 的相对浓度较高，表明单个 BDE 同系物的吸收、代谢和/或排泄具有选择性。明确地说，不能排除BDE-99在体内可能转化为BDE-47，以及BDE-154可能在体内转化为BDE-153。本大鼠研究中的内部剂量可与报道的人血清 PBDE 剂量进行比较。人血清/血液水平范围很广，欧洲背景样品中的总PBDE/克脂质为 3 至 6 纳克总PBDE/克脂质，美国样品中的总浓度高出约 10 倍，而美国收集的样品的上限水平则高出 100 倍（300-600 纳克/克脂质）。因此，对大鼠的效应水平与对人类的暴露水平之间的差值差异很大，商大约为 1000 到 100000。一般来说，可以预期该差值低于使用外部剂量指标的情况。由于最近的研究表明，比我们研究中产生效果的剂量更低的剂量对后代的影响，因此预计利润率甚至会更低。最后，应该指出的是，人类在日常生活中已经接触到多种化学物质的混合物，这一事实使这种比较变得复杂。 (c) 2006 Elsevier Ltd. 保留所有权利。
In experimental models, polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants, have caused effects in a number of biological end-points, including neurobehavioural effects, disturbances in thyroid and steroid hormone homeostasis, and other steroid-related effects. Almost exclusively, only external dose metrics (dose per body weight basis) have been studied in connection to the observed effects. In this study we report on new analyses of plasma PBDE levels in surplus samples from earlier studies on thyroid hormones (TH) in exposed rodents. Female, 7-week old Sprague-Dawley rats were given either Bromkal 70-5 DE (Study 1; 18 or 36 mg/ kg bw/day) or BDE-47 (Study 11; 1, 6 or 18 mg/kg bw/day) daily by gavage for two weeks. At an external dose of 18 mg/kg bw/day significant TH effects (decreased plasma free thyroxin levels) were observed in both studies, corresponding to an internal (plasma) dose of 463 mu g sumPBDE/g lipid (Study I) or 421 mu g BDE-47/g lipid (Study II). If we compare the contribution of different BDE congeners to the total BDE level in rat plasma after Bromkal exposure (Study II), and in the Bromkal mixture itself, the most important congener in the Bromkal mixture were also found in plasma. However, the relative concentration of BDE-99 was lower, and that of BDE-153 was higher, than that of the mixture, indicating selectivity in uptake, metabolism and/or excretion of the individual BDE congeners. Explicitly, the possible in vivo conversion of BDE-99 to BDE-47, and of BDE-154 to BDE-153 could not be excluded. The internal dose in the present rat study could be compared to reported human serum doses of PBDE. Human serum/blood levels have a wide range, from 3 to 6 ng sumPBDE/g lipid in background samples from Europe, about 10 times higher in US sample, and up to 100 times higher (300-600 ng/g lipid) in upper-end levels in collected samples from USA. As a consequence, the margin between effects levels in the rat and exposure levels in man varies widely, with a quotient roughly from 1000 to 100000. Generally, it could be expected that this margin is lower than if external dose metrics would be used. An even lower margin could be expected as recent studies have shown effects in offspring at lower doses than those giving effects in our studies. Lastly, it should be noted that humans are already exposed to a mixture of chemicals in daily life, a fact that complicates this kind of comparison. (c) 2006 Elsevier Ltd. All rights reserved.