In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths
In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths
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DOI：
10.1016/j.toxlet.2013.01.025
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发表时间：
2013-04-12
影响因子：
3.5
通讯作者：
Lampen, Alfonso
中科院分区：
文献类型：
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作者：
Buhrke, Thorsten;Kibellus, Anja;Lampen, Alfonso
全氟辛酸(PFOA)用于生产含氟聚合物(PFT)。由于它的毒性，人们建议用碳链长度较短的同系物取代其工业应用中的物质，与全氟辛酸相比，这些同系物的毒性较小，然而，到目前为止，较小的全氟辛酸同系物的表征很差。在这项研究中，我们对碳链长度从4个到12个碳原子的全氟化羧酸(PFCA)的毒性进行了比较分析。以人肝癌细胞株HepG2作为体外培养的人肝细胞模型，可以发现PFCA的碳链长度与其细胞毒性呈正相关。然而，没有迹象表明细胞毒性的凋亡机制。所有接受调查的PFCA在两项独立的遗传毒性测试中均为阴性。作为一种众所周知的过氧化物酶体增殖剂，本研究中测试的另一种PFCA也被证明能够激活人过氧化物酶体增殖物激活受体α(PPARα)，其中PFOA具有最高的激活PPARα的潜力。此外，化合物对PPARγ的激活能力较弱，对PPAR Delta几乎没有激活作用。综上所述，体外研究表明，碳链较短的全氟辛酸似乎比全氟辛酸毒性更小。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
Perfluorooctanoic acid (PFOA) is in use for the production of fluoropolymers (PFT). Due to its toxic properties it was proposed to replace the substance in its industrial applications by homologous compounds with shorter carbon chain length that were supposed to be less toxic compared to PFOA, however, the smaller PFOA homologs are poorly characterized so far. In this study we have conducted a comparative analysis of the toxicity of perfluorinated carboxylic acids (PFCA) with a carbon chain length ranging from four to twelve carbon atoms. By using the human hepatocarcinoma cell line HepG2 as an in vitro model for human hepatocytes we could show a positive correlation between the carbon chain length of the respective PFCA and its cytotoxicity. There was, however, no indication of an apoptotic mechanism for cytotoxicity. All PFCA under investigation were negative in two independent genotoxicity assays. As PFOA, being a well-known peroxisome proliferator, the other PFCA tested in this study were also shown to activate human peroxisome proliferator-activated receptor alpha (PPAR alpha) with PFOA having the highest potential of PPAR alpha activation. Moreover, the compounds showed weak potential to activate PPAR gamma and hardly activated PPAR delta. Taken together, the in vitro study revealed that PFCA with a shorter carbon chain length seem to be less toxic than PFOA. (C) 2013 Elsevier Ireland Ltd. All rights reserved.