Abstract
BACKGROUND: Bioaccumulation, widespread usage, and adverse human health effects emphasize per- and polyfluoroalkyl substances (PFAS) as an important public health concern. There is a need for an aggregate PFAS exposure measure due to the increasing diversity of structures. Aggregate measures are important for informing clinical care, biomonitoring, and research standardization. Current approaches for human biomonitoring of PFAS include targeting and quantifying a limited number of molecules and estimating exposure based on summed concentrations or statistical modeling. Extractable organofluorine (EOF) has been proposed as an aggregate PFAS biomarker that quantifies the total organically bound fluorine in a sample, encompassing PFAS regardless of knowing the exact chemical structures. However, EOF in human biomonitoring studies or environmental epidemiology is limited. OBJECTIVE: The objective of this study is to comprehensively assess human studies that measure EOF and target PFAS in the same sample by conducting a literature search, data extraction, and secondary data analysis. METHODS: We assessed the correlation of three aggregate PFAS exposure metrics with each other: EOF, adjusted summed concentrations of PFAS identified by the National Academies of Science Engineering and Medicine (NASEM), and PFAS burden scores. RESULTS: Across 8 published studies from US, Asia and Europe with 163 samples, EOF concentrations were higher than NASEM summed PFAS concentrations, and EOF was strongly associated with PFAS burden scores and NASEM sum. EOF does not identify or differentiate non-PFAS sources of fluorine which limits identification of individual molecules and their potential toxicity. SIGNIFICANCE: Correlations between EOF, summed targeted PFAS concentrations, and PFAS burden scores demonstrated that EOF is a practical tool for estimating PFAS exposure and identifying individuals with high exposure to PFAS. Thus, EOF could be utilized for identifying individuals or sub-populations with high aggregate PFAS exposure. Practical considerations in laboratory analyses, including instrumentation, sample matrix, and sample extraction procedure, remain potential barriers to widespread implementation of EOF as a biomonitoring tool. IMPACT: This study highlights the potential of extractable organofluorine (EOF) as a comprehensive biomarker for assessing aggregate PFAS exposure in human populations. By analyzing data from eight studies across the US, Asia, and Europe, we found that EOF concentrations were higher than summed PFAS concentrations and correlated strongly with PFAS burden scores. Although EOF does not identify specific fluorine sources, its strong associations suggest it is a practical tool for detecting high PFAS exposure. While EOF offers promise for identifying at-risk populations, practical challenges in laboratory analyses may limit its widespread use in biomonitoring programs.