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

Phospholipid Levels Predict the Tissue Distribution of Poly- and Perfluoroalkyl Substances in a Marine Mammal

Abstract. Exposure to poly- and perfluoroalkyl substances (PFASs) has been linked to many negative health impacts in humans and wildlife. Unlike neutral hy

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

Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects.

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

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

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.

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.

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

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

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

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

County-level associations between drinking water PFAS contamination and COVID-19 mortality in the United States

Epidemiologic and animal studies both support relationships between exposures to per- and polyfluoroalkyl substances (PFAS) and harmful effects on the immune system. Accordingly, PFAS have been identified as potential environmental risk factors for adverse COVID-19 outcomes.

The Air That We Breathe: Neutral and Volatile PFAS in Indoor Air

Abstract. Sources of exposure to per- and polyfluorinated alkyl substances (PFAS) include food, water, and, given that humans spend typically 90% of their

Benchmark dose calculations for PFAS exposure based on two data sets on immunotoxic effects

Exposure to perfluorinated alkylate substances (PFAS) is associated with harmful effects on human health, including developmental immunotoxicity. This outcome was chosen as the critical effect by the European Food Safety Authority (EFSA), which calculated a new joint reference dose for four PFAS using a Benchmark Dose (BMD) analysis of a study of 1-year old children. However, the U.S. Environmental Protection Agency (EPA) recently proposed much lower exposure limits.

Bioconcentration of Per- and Polyfluoroalkyl Substances and Precursors in Fathead Minnow Tissues Environmentally Exposed to Aqueous Film-Forming Foam–Contaminated Waters

Abstract Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with toxicity in wildlife and negative health effects in humans. Decades of fire training activity at Joint Base Cape Cod (MA, USA) incorporated the use of aqueous film-forming foam (AFFF), which resulted in long-term PFAS contamination of sediments, groundwater, and hydrologically connected surface waters. To explore the bioconcentration potential of PFAS in complex environmental mixtures, a mobile laboratory was established to evaluate the bioconcentration of PFAS from AFFF-impacted groundwater by flow-through design. Fathead minnows (n = 24) were exposed to PFAS in groundwater over a 21-day period and tissue-specific PFAS burdens in liver, kidney, and gonad were derived at three different time points. The ∑PFAS concentrations in groundwater increased from approximately 10,000 ng/L at day 1 to 36,000 ng/L at day 21. The relative abundance of PFAS in liver, kidney, and gonad shifted temporally from majority perfluoroalkyl sulfonamides (FASAs) to perfluoroalkyl sulfonates (PFSAs). By day 21, mean ∑PFAS concentrations in tissues displayed a predominance in the order of liver > kidney > gonad. Generally, bioconcentration factors (BCFs) for FASAs, perfluoroalkyl carboxylates (PFCAs), and fluorotelomer sulfonates (FTS) increased with degree of fluorinated carbon chain length, but this was not evident for PFSAs. Perfluorooctane sulfonamide (FOSA) displayed the highest mean BCF (8700 L/kg) in day 21 kidney. Suspect screening results revealed the presence of several perfluoroalkyl sulfinate and FASA compounds present in groundwater and in liver for which pseudo-bioconcentration factors are also reported. The bioconcentration observed for precursor compounds and PFSA derivatives detected suggests alternative pathways for terminal PFAS exposure in aquatic wildlife and humans. Environ Toxicol Chem 2024;43:1795–1806. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Flow-through dosing experiments utilizing aqueous film-forming foam (AFFF)–contaminated groundwater revealed positive linear correlations between fluorinated carbon chain length and logarithm-transformed bioconcentration factors (BCFs) for perfluoroalkyl sulfonamides identified in fathead minnow (Pimephales promelas) liver via target analysis and suspect screening using high-resolution mass spectrometry. FBSA = perfluorobutane sulfonamide; FHxSA = perfluorohexane sulfonamide; FOSA = perfluorooctane sulfonamide; FPeSA= perfluoropentane sulfonamide; FPrSA = perfluoropropane sulfonamide.

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.

Legacy and Novel Per- and Polyfluoroalkyl Substances in Juvenile Seabirds from the U.S. Atlantic Coast

Abstract. Per- and polyfluoroalkyl substances (PFAS) are anthropogenic, globally distributed chemicals. Legacy PFAS, including perfluorooctane sulfonate (P