







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

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

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.

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

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

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

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

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.
Weight loss relapse associated with exposure to perfluorinated alkylate substances
Abstract Objective The purpose of this study was to test the hypothesis that perfluorinated alkylate substance (PFAS) exposures are associated with body weight increases in a dietary intervention study. Methods In the DioGenes trial, adults with obesity first lost at least 8% of their body weight and then completed at least 26 weeks on a specific diet. Concentrations of five major PFASs were assessed in plasma samples from study baseline. Results In 381 participants with complete data, plasma concentrations averaged 2.9 ng/mL and 1.0 ng/mL for perfluorooctanoic acid (PFOA) and perfluorohexanesulfonic acid (PFHxS), respectively. A doubling in plasma PFOA was associated with an increase in weight at 26 weeks by 1.50 kg (95% CI: 0.88–2.11), with an increase of 0.91 kg (95% CI: 0.54–1.27) for PFHxS, independent of diet groups and sex. Associations for other PFASs were in the same direction and significant, although not after adjustment for PFOA and PFHxS. Weight changes associated with elevated PFAS exposures were similar to or larger than average changes ascribed to the different diet groups. Conclusions Elevated plasma concentrations of PFOA and PFHxS were associated with increased weight gain that exceeded those related to the diets. Obesogenic PFASs may cause weight gain and thus contribute to the obesity pandemic.

Passive Sampler Derived Profiles and Mass Flows of Perfluorinated Alkyl Substances (PFASs) across the Fram Strait in the North Atlantic
Abstract. Per- and polyfluorinated alkyl substances (PFAS) are a family of pollutants of high concern due to their ubiquity and negative human health impac

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

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

Estimated exposure to perfluoroalkyl substances during infancy and serum-adipokine concentrations in later childhood
Perfluoroalkyl substances (PFASs) are transferred through human milk and may cause elevated exposure during infancy. Given the lack of early postnatal blood samples, PFAS concentrations can be estimated to serve as predictors of subsequent metabolic toxicity.

Calibration of Perfluorinated Alkyl Acid Uptake Rates by a Tube Passive Sampler in Water
Abstract. Per- and polyfluoroalkyl substances (PFAS) are a group of 4000+ man-made compounds of great concern due to their environmental ubiquity and adver

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.
