Analysis of PFOA in dosed CD1 mice: Part 1. Methods development for the analysis of tissues and fluids from pregnant and lactating mice and their pups
Analysis of PFOA in dosed CD1 mice: Part 1. Methods development for the analysis of tissues and fluids from pregnant and lactating mice and their pups
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DOI：
10.1016/j.reprotox.2008.10.006
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发表时间：
2009-06-01
影响因子：
3.3
通讯作者：
Strynar, Mark J.
中科院分区：
文献类型：
--
作者：
Reiner, Jessica L.;Nakayama, Shoji F.;Strynar, Mark J.
涉及全氟辛酸（PFOA）分析的研究数量最近有所增加，因为在世界各地的人类血液样本中经常检测到全氟辛酸。最近对小鼠的研究表明，与对照动物相比，在怀孕期间给怀孕的母鼠服用PFOA会导致胎鼠的剂量依赖性死亡率，存活幼崽的新生儿体重减少，以及随后的乳腺发育缺陷。与这些端点相关的母鼠和幼崽体内PFOA的实际负荷尚未确定，部分原因是缺乏对这些基质的可靠分析方法。本研究的目的是开发具有可接受性能特征的可靠方法，用于分析与怀孕小鼠研究相关的几种基质中的全氟辛酸。分离母鼠和幼鼠血清、羊水、尿液、乳汁、乳腺组织和全鼠幼鼠进行方法开发和分析。该方法具有良好的准确度（92.1 ~ 111%）和重复性（相对标准偏差4.3 ~ 21%），对今后的研究具有重要意义。然后将这些方法应用于给药的动物体液和组织，以便对子宫内的药代动力学进行全面评估。由此产生的血清、羊水、尿液、乳汁、乳腺组织和整个幼犬匀浆中PFOA的组织特异性测量结果将用于更完整地描述最敏感的健康结果的剂量-反应关系，并为正在开发和评估的药代动力学模型提供信息。Elsevier Inc.出版。
The number of studies involving the analysis of perfluorooctanoic acid (PFOA) has increased recently because PFOA is routinely detected in human blood samples from around the world. Recent studies with mice have shown that dosing pregnant dams with PFOA during gestation gives rise to a dose-dependent mortality in the litters, a reduction in neonatal body weight for the surviving pups, and subsequent deficits in mammary gland development when compared to control animals. The actual body burdens of PFOA in dams and pups associated with these endpoints have not been determined, in part due to a lack of robust analytical methods for these matrices. The goal of the current study was to develop reliable methods with acceptable performance characteristics for the analysis of PFOA in several matrices relevant to pregnant mouse studies. Dam and pup serum, amniotic fluid, urine, milk, mammary tissue, and whole mouse pups were isolated for method development and analysis. The resulting method provided excellent accuracy (92.1-111%) and reproducibility (relative standard deviation 4.3-21%) making them very useful for future studies. These methods were then applied to dosed animal fluids and tissues in order to conduct a thorough evaluation of the pharmacokinetics in utero. Resulting tissue specific measurements of PFOA in serum, amniotic fluid, urine, milk, mammary tissue, and whole pup homogenate will be used to more completely describe the dose-response relationships for the most sensitive health outcomes and inform pharmacokinetic models that are being developed and evaluated. Published by Elsevier Inc.