Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

Understanding Mechanisms of PFAS Absorption, Distribution, and Elimination Using a Physiologically Based Toxicokinetic Model

Abstract. Exposures to some per- and polyfluoroalkyl substances (PFAS), including perfluoroalkyl acids (PFAA), have been associated with diverse adverse he

Exposure to per-fluoroalkyl and polyfluoroalkyl substances leads to immunotoxicity: epidemiological and toxicological evidence

In this perspective, we evaluate key and emerging epidemiological and toxicological data concerning immunotoxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) and seek to reconcile conflicting conclusions from two reviews published in 2016. We summarize ways that immunosuppression and immunoenhancement are defined and explain how specific outcomes are used to evaluate immunotoxicity in humans and experimental animals. We observe that different approaches to defining immunotoxicological outcomes, particularly those that do not produce clinical disease, may lead to different conclusions from epidemiological and toxicological studies. The fundamental point that we make is that aspects of epidemiological studies considered as limitations can be minimized when data from toxicological studies support epidemiological findings. Taken together, we find that results of epidemiological studies, supported by findings from toxicological studies, provide strong evidence that humans exposed to PFOA and PFOS are at risk for immunosuppression.

Binding of Per- and Polyfluoroalkyl Substances (PFAS) to Serum Proteins: Implications for Toxicokinetics in Humans

Abstract. Per- and polyfluoroalkyl substances (PFAS) are a diverse class of highly persistent anthropogenic chemicals that are detectable in the serum of m

How Do We Measure Poly- and Perfluoroalkyl Substances (PFASs) at the Surface of Consumer Products?

Abstract. Exposures to poly- and perfluoroalkyl substances (PFASs) have been linked to metabolic disruption, immunotoxicity, and cancer in humans. PFASs ar

Unbound Fractions of PFAS in Human and Rodent Tissues: Rat Liver a Suitable Proxy for Evaluating Emerging PFAS?

Abstract. Adverse health effects associated with exposures to perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a concern for public health and are

Occurrence of Major Perfluorinated Alkylate Substances in Human Blood and Target Organs

Abstract. Human exposure to perfluorinated alkylate substances (PFASs) is usually assessed from the concentrations in serum or plasma, assuming one-compart

A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects

Here, we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.

Liver and Intestinal Fatty Acid Binding Proteins Are Not Critical for Perfluorooctanesulfonate (PFOS) Tissue Distribution and Elimination in Mice

Abstract. Perfluorooctanesulfonate (PFOS) is a persistent environmental pollutant in the per- and polyfluoroalkyl substances (PFAS) class, known to accumul

Stability of Per- and Polyfluoroalkyl Substances in Solvents Relevant to Environmental and Toxicological Analysis

Abstract. Per- and polyfluoroalkyl substances (PFASs) are widely used anthropogenic chemicals. For environmental and toxicological analysis, it is importan

PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding

Abstract. We synthesize current understanding of the magnitudes and methods for assessing human and wildlife exposures to poly‐ and perfluoroalkyl substanc

Tap Water Contributions to Plasma Concentrations of Poly- and Perfluoroalkyl Substances (PFAS) in a Nationwide Prospective Cohort of U.S. Women

Abstract Background: Between 2013 and 2015, concentrations of poly- and perfluoroalkyl substances (PFAS) in public drinking water supplies serving at least six million individuals exceeded the level set forth in the health advisory established by the U.S. Environmental Protection Agency. Other than data reported for contaminated sites, no systematic or prospective data exist on the relative source contribution (RSC) of drinking water to human PFAS exposures. Objectives: This study estimates the RSC of tap water to overall PFAS exposure among members of the general U.S. population. Methods: We measured concentrations of 15 PFAS in home tap water samples collected in 1989–1990 from 225 participants in a nationwide prospective cohort of U.S. women: the Nurses’ Health Study (NHS). We used a one-compartment toxicokinetic model to estimate plasma concentrations corresponding to tap water intake of PFAS. We compared modeled results with measured plasma PFAS concentrations among a subset of 110 NHS participants. Results: Tap water perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) were statistically significant predictors of plasma concentrations among individuals who consumed ≥8 cups of tap water per day. Modeled median contributions of tap water to measured plasma concentrations were: PFOA 12% (95% probability interval 11%–14%), PFNA 13% (8.7%–21%), linear perfluorooctanesulfonic acid (nPFOS) 2.2% (2.0%–2.5%), branched perfluorooctanesulfonic acid (brPFOS) 3.0% (2.5%–3.2%), and perfluorohexanesulfonic acid (PFHxS) 34% (29%–39%). In five locations, comparisons of PFASs in community tap water collected in the period 2013–2016 with samples from 1989–1990 indicated increases in quantifiable PFAS and extractable organic fluorine (a proxy for unquantified PFAS). Conclusions: Our results for 1989–1990 compare well with the default RSC of 20% used in risk assessments for legacy PFAS by many agencies. Future evaluation of drinking water exposures should incorporate emerging PFAS. https://doi.org/10.1289/EHP4093

Addressing Urgent Questions for PFAS in the 21st Century

Abstract. Despite decades of research on per- and polyfluoroalkyl substances (PFAS), fundamental obstacles remain to addressing worldwide contamination by

Delayed discovery, dissemination, and decisions on intervention in environmental health: a case study on immunotoxicity of perfluorinated alkylate substances

Identification and characterization of environmental hazards that impact human health must rely on the best possible science to inform and inspire appropriate public health intervention. The perfluorinated alkylate substances (PFASs) are persistent emerging pollutants that are now being recognized as important human health hazards. Although the PFASs have been produced for over 60 years, academic research on environmental health aspects has appeared only in the most recent 10 years or so. In the meantime, these persistent chemicals accumulated in the global environment. Some early studies e.g., on population exposures and toxicity, were not released to the public until after year 2000. Still, the first PFAS risk assessments ignored these reports and relied on scant journal publications. The first guidelines and legal limits for PFAS exposure, e.g., from drinking water, were proposed 10 years ago. They have decreased substantially since then, but remain higher than suggested by data on human adverse effects, especially on the immune system, that occur at background exposure levels. By now, the best-known PFASs are being phased out, and related PFASs are being introduced as substitutes. Given the substantial delays in discovery of PFAS toxicity, in dissemination of findings, and in regulatory decisions, PFAS substitutes and other persistent industrial chemicals should be subjected to prior scrutiny before widespread usage.

Per- and Polyfluoroalkyl Substances in Human Liver and Serum

<p> This dataset contains measured concentrations of 54 targeted per- and polyfluoroalkyl substances (PFAS) in 211 human liver samples and 18 matched serum samples, determined using liquid chromatography–tandem high-resolution mass spectrometry (LC-HRMS/MS). The dataset is supplemented with anonymized demographic and physiological information for the matched samples. </p> <p>The dataset comprises:</p> <ul> <li>(i) a list of targeted PFAS compounds included in the LC-MS/MS analyses for both liver and serum,</li> <li>(ii) 12 raw data files generated from LC-MS/MS analyses,</li> <li>(iii) information on individual samples, including quality control samples such as blanks, continuous calibration verification samples, and matrix spikes,</li> <li>(iv) quality control criteria thresholds for extracted internal standard recoveries, ion abundance ratios, and retention time shifts, as well as the input parameters used to process the raw data files,</li> <li>(v) combined processed results of PFAS contamination levels, and</li> <li>(vi) anonymized demographic and physiological information.</li> </ul> <p> The combined processed results (v) were generated by processing the raw data files (ii) using a Jupyter-based data cleaning and QA/QC pipeline for targeted PFAS LC-MS/MS, as referenced in the Related Publications. Sample information (iii), quality control criteria thresholds, and processing input parameters (iv) were used as inputs to run this pipeline. </p> <p> Raw data files are tagged as <em>raw data</em>. File names indicate the date of sample preparation for each batch (YYYYMMDD), the matrix type (liver or serum), and the analytical method used (core or extended). </p> <p> The <strong>core method</strong> measures contamination levels of the following PFAS compounds: </p> <p> PFBA, PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUdA, PFDoA, PFTrDA, PFTeDA, PFBS, PFPeS, L-PFHxS, Br-PFHxS, PFHpS, L-PFOS, Br-PFOS, PFNS, PFDS, FBSA, FPeSA, FHxSA, FHpSA, FOSA, 4:2 FTS, 6:2 FTS, 8:2 FTS, 10:2 FTS. </p> <p> The <strong>extended method</strong> measures contamination levels of: </p> <p> PFPrA, 3:3 FTCA, 5:3 FTCA, 7:3 FTCA, FOEA, PFPrS, MeFBSA, N-EtFBSA-M, L-N-MeFOSAA, Br-N-MeFOSAA, L-N-EtFOSAA, Br-N-EtFOSAA, MeFOSA, EtFOSA, HFPO-DA, DONA, 9ClPF3ONS, 11ClPF3OUdS, 3,6-OPFHpA, PF4OPeA, PF5OHxA, PFECHS, PFEESA, N-AP-FHxSA, N-TAmP-FHxSA. </p> <p> Sample information, quality control thresholds, and simulation parameters are tagged as <em>simulation input</em>. Files ending in <em>_liver.csv</em> or <em>_serum.csv</em> apply only to liver or serum samples, respectively; files without these suffixes apply to both matrix types. </p> <p> Combined processed results across all batches for liver and serum samples are tagged as <em>processed data</em>. Specimen demographic data are tagged accordingly. </p>

High organofluorine concentrations in municipal wastewater affect downstream drinking water supplies for millions of Americans

Wastewater receives per- and polyfluoroalkyl substances (PFAS) from diverse consumer and industrial sources, and discharges are known to be a concern for drinking water quality. The PFAS family includes thousands of potential chemical structures containing organofluorine moieties. Exposures to a few well-studied PFAS, mainly perfluoroalkyl acids (PFAA), have been associated with increased risk of many adverse health outcomes, prompting federal drinking water regulations for six compounds in 2024. Here, we find that the six regulated PFAS (mean = 7 to 8%) and 18 measured PFAA (mean = 11 to 21%) make up only a small fraction of the extractable organofluorine (EOF) in influent and effluent from eight large municipal wastewater treatment facilities. Most of the EOF in influent (75%) and effluent (62%) consists of mono- and polyfluorinated pharmaceuticals. The treatment technology and sizes of the treatment facilities in this study are similar to those serving 70% of the US population. Despite advanced treatment technologies, the maximum EOF removal efficiency among facilities in this work was <25%. Extrapolating our measurements to other large facilities across the United States results in a nationwide EOF discharge estimate of 1.0 to 2.8 million moles F y −1 . Using a national model that simulates connections between wastewater discharges and downstream drinking water intakes, we estimate that the sources of drinking water for up to 23 million Americans could be contaminated above regulatory thresholds by wastewater-derived PFAS alone. These results emphasize the importance of further curbing ongoing PFAS sources and additional evaluations of the fate and toxicity of fluorinated pharmaceuticals.

Guideline levels for PFOA and PFOS in drinking water: the role of scientific uncertainty, risk assessment decisions, and social factors

Communities across the U.S. are discovering drinking water contaminated by perfluoroalkyl and polyfluoroalkyl substances (PFAS) and determining appropriate actions. There are currently no federal PFAS drinking water standards despite widespread drinking water contamination, ubiquitous population-level exposure, and toxicological and epidemiological evidence of adverse health effects. Absent federal PFAS standards, multiple U.S. states have developed their own health-based water guideline levels to guide decisions about contaminated site cleanup and drinking water surveillance and treatment. We examined perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) water guideline levels developed by the U.S. Environmental Protection Agency (EPA) and state agencies to protect people drinking the water, and summarized how and why these levels differ. We referenced documents and tables released in June 2018 by the Interstate Technology and Regulatory Council (ITRC) to identify states that have drinking water and groundwater guideline levels for PFOA and/or PFOS that differ from EPA’s health advisories (HAs). We also gathered assessment documents from state websites and contacted state environmental and health agencies to identify and confirm current guidelines. Seven states have developed their own water guideline levels for PFOA and/or PFOS ranging from 13 to 1000 ng/L, compared to EPA’s HA of 70 ng/L for both compounds individually or combined. We find that the development of PFAS guideline levels via exposure and hazard assessment decisions is influenced by multiple scientific, technical, and social factors, including managing scientific uncertainty, technical decisions and capacity, and social, political, and economic influences from involved stakeholders. Assessments by multiple states and academic scientists suggest that EPA’s HA is not sufficiently protective. The ability of states to develop their own guideline levels and standards provides diverse risk assessment approaches as models for other state and federal regulators, while a sufficiently protective, scientifically sound, and enforceable federal standard would provide more consistent protection.