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Kamlesh Sodani¹, Bas Ter Braak², Sabine Hartvelt²

¹Product Stewardship and Toxicology, Honeywell Energy and Sustainability Solutions, 115 Tabor Road, Morris Plains, NJ 07950, United States.

Toxicology letters

|February 11, 2025

概括

和多基基物质 (PFAS) 的碳链长度显著影响其毒性. 像PFOA这样的长链PFAS更有细胞毒性并诱导压力,而超短链PFAS,如三酸 (TFA),具有最小的毒性.

科学领域:

环境科学环境科学
毒理学毒理学毒理学
生物化学生物化学

背景情况:

和多醇基物质 (PFAS) 是持久性环境污染物,具有不同的毒理特征.
了解PFAS化学结构和毒性之间的关系对于风险评估至关重要.
现有研究表明,不同PFAS的毒理作用模式 (MoA) 不同.

研究的目的:

研究PFAS碳链长度对体外毒性和细胞应激反应的影响.
为了比较长链与超短链PFAS的细胞毒性和致死性潜力.
阐明不同PFAS所影响的特定细胞通路.

主要方法:

利用ToxProfiler测定来评估细胞应激反应 (氧化应激,ER应激,自等). 在暴露于八种不同碳链长度 (C2-C10) 的PFAS的人类细胞中.
使用人类诱导多能干细胞 (hiPSCs) 的 ReproTracker 试验来评估 perfluorooctanoic 酸 (PFOA; C8) 和三乙酸 (TFA; C2) 的病原性.
监测hiPSCs分化为心肌细胞,肝细胞和神经状细胞,以确定发育性毒性危险.

主要成果:

长链PFAS (C8-C10),包括PFOA,表现出更高的细胞毒性,主要诱导内分泌网膜 (ER) 和氧化应激.
碳链长度为C4-C7的PFAS主要触发了自.
超短链PFAS (TFA;C2和 perfluoropropionic acid;PFPrA;C3) 在测试度下没有显示出细胞毒性或压力报告者的激活.
在hiPSC中,PFOA暴露破坏了肝细胞和神经皮质分化,而TFA没有显著影响.

结论:

PFAS碳链长度是它们体外毒性的关键决定因素.
超短链PFAS,以TFA为例,与长链PFAS相比,毒性明显较低.
这些发现强调了在PFAS风险评估中需要进行结构-活动关系研究的必要性.

关键词:

发展性毒性发展性毒性新方法方法 (NAM)在PFAS中,我们可以使用PFAS.在TFA中,TFA是TFA.超短链PFAS是一种超短链PFAS.

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