Chang Che-Jung, Young Anna S, Keil Alexander, Mullins Catherine E, Liang Donghai, Zhao Shanshan, Jones Dean P, Hu Xin, Walker Douglas I, White Alexandra J
Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States; DLH LLC, Bethesda, MD, United States.
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, United States.
Environ Int. 2025 Jul;201:109590. doi: 10.1016/j.envint.2025.109590. Epub 2025 Jun 6.
As legacy per- and polyfluoroalkyl substances (PFAS) are phased out, numerous substitutes have emerged, raising concerns about their potential health impacts. Using targeted and untargeted approaches, we evaluated plasma PFAS on an -omic scale, examining temporal variability and associated metabolomic disruptions. A total of 400 blood samples from 200 Sister Study participants (collected in 2007-2008 and 2013-2014) were analyzed using liquid chromatography with high-resolution mass spectrometry. Temporal variability was assessed using Spearman correlations and intraclass correlation coefficients. Network analysis, metabolome-wide association studies, and pathway analysis were used to evaluate the impacts of PFAS mixtures on the human metabolome. We detected 24 legacy PFAS via the targeted approach and 1,802 features annotated as potential PFAS via the untargeted approach (21 confirmed by reference standards). While legacy PFAS demonstrated low temporal variability, novel PFAS, especially those that have increased in abundance over time, demonstrated greater temporal variability. The legacy PFAS mixture was associated with lipid and amino acid metabolism, while other PFAS mixtures consisting of novel PFAS affected a wider range of metabolic pathways in addition to amino and lipid metabolism, such as carbohydrate, cofactor and vitamin, and endocrine metabolism. These findings underscore the need for further research on these novel PFAS and their health effects.
随着传统全氟和多氟烷基物质（PFAS）的逐步淘汰，众多替代品应运而生，这引发了人们对其潜在健康影响的担忧。我们采用靶向和非靶向方法，在组学规模上评估血浆中的PFAS，研究其时间变异性以及相关的代谢组学紊乱情况。使用液相色谱与高分辨率质谱联用技术，对来自200名姐妹研究参与者的400份血液样本（于2007 - 2008年和2013 - 2014年采集）进行了分析。通过斯皮尔曼相关性和组内相关系数评估时间变异性。运用网络分析、代谢组全关联研究和通路分析来评估PFAS混合物对人体代谢组的影响。通过靶向方法我们检测到24种传统PFAS，通过非靶向方法检测到1802个被注释为潜在PFAS的特征峰（其中21个经参考标准物确认）。传统PFAS的时间变异性较低，而新型PFAS，尤其是那些随着时间推移丰度增加的新型PFAS，表现出更大的时间变异性。传统PFAS混合物与脂质和氨基酸代谢相关，而其他由新型PFAS组成的PFAS混合物除了影响氨基酸和脂质代谢外，还影响更广泛的代谢途径，如碳水化合物、辅因子和维生素以及内分泌代谢。这些发现强调了对这些新型PFAS及其健康影响进行进一步研究的必要性。
