Per- and polyfluoroalkyl substances, apolipoproteins and the risk of coronary heart disease in US men and women

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

Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women

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

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

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.

Severity of COVID-19 at elevated exposure to perfluorinated alkylates

Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic and may contribute to an association with disease severity. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30–70 years with known SARS-CoV-2 infection. The PFAS concentrations measured at the background exposures included five PFASs known to be immunotoxic. Register data was obtained to classify disease status, other health information, and demographic variables. We used ordered logistic regression analyses to determine associations between PFAS concentrations and disease outcome. Results Plasma-PFAS concentrations were higher in males, in subjects with Western European background, and tended to increase with age, but were not associated with the presence of chronic disease. Of the study population, 108 (33%) had not been hospitalized, and of those hospitalized, 53 (16%) had been in intensive care or were deceased. Among the five PFASs considered, perfluorobutanoic acid (PFBA) showed an unadjusted odds ratio (OR) of 2.19 (95% confidence interval, CI, 1.39–3.46) for increasing severities of the disease. Among those hospitalized, the fully adjusted OR for getting into intensive care or expiring was 5.18 (1.29, 20.72) when based on plasma samples obtained at the time of diagnosis or up to one week before. Conclusions Measures of individual exposures to immunotoxic PFASs included short-chain PFBA known to accumulate in the lungs. Elevated plasma-PFBA concentrations were associated with an increased risk of a more severe course of COVID-19. Given the low background exposure levels in this study, the role of exposure to PFASs in COVID-19 needs to be ascertained in populations with elevated exposures.

Shifting Global Exposures to Poly- and Perfluoroalkyl Substances (PFASs) Evident in Longitudinal Birth Cohorts from a Seafood-Consuming Population

Abstract. Rapid declines in legacy poly- and perfluoroalkyl substances (PFASs) have been reported in human populations globally following changes in produc

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

Are Fluoropolymers Really of Low Concern for Human and Environmental Health and Separate from Other PFAS?

Abstract. Fluoropolymers are a group of polymers within the class of per- and polyfluoroalkyl substances (PFAS). The objective of this analysis is to evalu

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

Life-course Exposure to Perfluoroalkyl Substances in Relation to Markers of Glucose Homeostasis in Early Adulthood

AbstractObjective. To investigate the prospective associations of life-course perfluoroalkyl substances (PFASs) exposure with glucose homeostasis at adulth

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.

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

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