Drinking Water–Associated PFAS and Fluoroethers and Lipid Outcomes in the GenX Exposure Study

Rosen, Emma M.; Kotlarz, Nadine; Knappe, Detlef R.U.; Lea, C. Suzanne; Collier, David N.; Richardson, David B.; Hoppin, Jane A.

doi:10.1289/ehp11033

Cited by 34 publications

(38 citation statements)

References 42 publications

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“…Endocrinic system Thyroid [217,[394][395][396]; steroid(cortisone) [397][398][399] and sex hormones [398,400,401] 5. Metabolism (a) Glucose [402]; type 2-diabetes [403][404][405][406]; gestational diabetes [213] (b) Fat [387,[407][408][409] (c) Bile acid [387] (d) Total and non-HDL cholesterol [410][411][412] 6. Fertility: toxicity to reproduction, embryotoxic, fetotoxic (a) Delayed occurrence of desired pregnancy/childlessness [413,414] (b) Miscarriage [415] (c) Lifelong effects on organ health and development of disease [416][417][418][419][420][421][422] (c) Pregnancy/mother: hypertension [423], preeclampsia [423][424][425] (d) Pregnancy/child: miscarriage [139,426,427], reduced birth weight [195,196,428], reduced fetal growth …”

Section: Affected Organ/function Consequencesmentioning

confidence: 99%

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

Brunn

Arnold²,

Körner

et al. 2023

Environ Sci Eur

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Background Per- and polyfluorinated alkyl substances (PFAS) have received increasing scientific and political attention in recent years. Several thousand commercially produced compounds are used in numerous products and technical processes. Due to their extreme persistence in the environment, humans and all other life forms are, therefore, increasingly exposed to these substances. In the following review, PFAS will be examined comprehensively. Results The best studied PFAS are carboxylic and sulfonic acids with chain lengths of C4 to C14, particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). These substances are harmful to aquatic fauna, insects, and amphibians at concentrations of a few µg/L or less, accumulate in organisms, and biomagnify in food webs. Humans, as the final link in numerous food chains, are subjected to PFAS uptake primarily through food and drinking water. Several PFAS have multiple toxic effects, particularly affecting liver, kidney, thyroid, and the immune system. The latter effect is the basis for the establishment of a tolerable weekly dose of only 4.4 ng/kg body weight for the sum of the four representatives PFOA, PFOS, perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) by the European Food Safety Authority (EFSA) in 2020. Exposure estimates and human biomonitoring show that this value is frequently reached, and in many cases exceeded. PFAS are a major challenge for analysis, especially of products and waste: single-substance analyses capture only a fragment of the large, diverse family of PFAS. As a consequence, sum parameters have gained increasing importance. The high mobility of per and polyfluorinated carboxylic and sulfonic acids makes soil and groundwater pollution at contaminated sites a problem. In general, short-chain PFAS are more mobile than long-chain ones. Processes for soil and groundwater purification and drinking water treatment are often ineffective and expensive. Recycling of PFAS-containing products such as paper and food packaging leads to carryover of the contaminants. Incineration requires high temperatures to completely destroy PFAS. After PFOA, PFOS and a few other perfluorinated carboxylic and sulfonic acids were regulated internationally, many manufacturers and users switched to other PFAS: short-chain representatives, per- and polyfluorinated oxo carboxylic acids, telomeric alcohols and acids. Analytical studies show an increase in environmental concentrations of these chemicals. Ultra-short PFAS (chain length C1–C3) have not been well studied. Among others, trifluoroacetic acid (TFA) is present globally in rapidly increasing concentrations. Conclusions The substitution of individual PFAS recognized as hazardous by other possibly equally hazardous PFAS with virtually unknown chronic toxicity can, therefore, not be a solution. The only answer is a switch to fluorine-free alternatives for all applications in which PFAS are not essential.

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Section: Affected Organ/function Consequencesmentioning

confidence: 99%

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

Brunn

Arnold²,

Körner

et al. 2023

Environ Sci Eur

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“…Interestingly, our study was broadly similar to the population study, which found that serum TC was proportional but not linearly related to GenX concentration, whereas TG was not correlated with GenX concentration. 40 By examining the expression of mRNAs and proteins of genes related to lipid metabolism after exposure to GenX in vivo, we found that mRNAs for the transport of fatty acidrelated proteins, fatty acid oxidation, and fatty acid synthesis had different responses in different exposure groups. This suggests that GenX has different toxic responses at different exposure concentrations.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover, this study found that both TC and TG were elevated in the liver after GenX exposure, as confirmed by previously published literature. , But changes in TG and TC in plasma were not consistent, with no change in TG and an increase in TC with increasing GenX dose. Interestingly, our study was broadly similar to the population study, which found that serum TC was proportional but not linearly related to GenX concentration, whereas TG was not correlated with GenX concentration …”

Section: Discussionmentioning

confidence: 99%

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

Shi,

Zhang,

et al. 2023

Chem. Res. Toxicol.

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Hexafluoropropylene oxide dimer acid (HFPO−DA; trade name GenX), as a substitute for perfluorooctanoic acid (PFOA), has been attracting increasing attention. However, its impact and corresponding mechanism on hepatic lipid metabolism are less understood. To investigate the possible mechanisms of GenX for hepatotoxicity, a series of in vivo and in vitro experiments were conducted. In in vivo experiment, male mice were exposed to GenX in drinking water at environmental concentrations (0.1 and 10 μg/L) and high concentrations (1 and 100 mg/L) for 14 weeks. In in vitro experiments, human hepatocellular carcinoma cells (HepG2) were exposed to GenX at 10, 160, and 640 μM for 24 and 48 h. GenX exposure via drinking water resulted in liver damage and disruption of lipid metabolism even at environmental concentrations. The results of triglycerides (TG) and total cholesterol (TC) in this study converged with the results of the population study, for which TG increased in the liver but unchanged in the serum, whereas TC increased in both liver and serum concentrations. KEGG and GO analyses revealed that the hepatotoxicity of GenX was associated with fatty acid transport, synthesis, and oxidation pathways and that Peroxisome Proliferator-Activated Receptor (PPARα) contributed significantly to this process. PPARα inhibitors significantly reduced the expression of CD36, CPT1β, PPARα, SLC27A1, ACOX1, lipid droplets, and TC, suggesting that GenX exerts its toxic effects through PPARα signaling pathway. In general, GenX at environmental concentrations in drinking water causes abnormal lipid metabolism via PPARα signaling pathway.

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“…7−10 Certain PFECAs have become ubiquitous in global surface waters, 11 exhibiting potential for both bioaccumulation within wildlife and subsequent biomagnification through the food chain. 12,13 Of particular concern, these compounds have been extensively detected in various human matrices, including blood, 14,15 urine, 16 and breast milk. 17 Emerging evidence suggests that long-chain PFECAs, such as HFPO homologues and perfluoro (3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA), demonstrate stronger bioaccumulation and toxicity effects compared to PFOA.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Per- and polyfluoroether carboxylic acids (PFECAs), representing a class of emerging per- and polyfluoroalkyl substances (PFASs), contain a variety of perfluoro/polyfluoroalkyl chains linked by single or multiple ether bonds . Recent evidence has indicated that PFECAs are becoming important alternatives to PFOA in fluoropolymer production. , Many PFECAs, such as hexafluoropropylene oxide dimer acid (HFPO–DA), 2-[2-(trifluoromethoxy)hexafluoropropoxy]tetrafluoropropanoic acid (C7 HFPO-TA), perfluoro-2-[(propoxy)propoxy]-1-propanoate (C9 HFPO-TA), and perfluoro-2-(perfluoromethoxy)propanoic acid (PMPA), have been identified as a principal or even predominant component in fluoropolymer industrial plant effluents and the surrounding environment. − Certain PFECAs have become ubiquitous in global surface waters, exhibiting potential for both bioaccumulation within wildlife and subsequent biomagnification through the food chain. , Of particular concern, these compounds have been extensively detected in various human matrices, including blood, , urine, and breast milk . Emerging evidence suggests that long-chain PFECAs, such as HFPO homologues and perfluoro (3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA), demonstrate stronger bioaccumulation and toxicity effects compared to PFOA. , However, research on short-chain compounds such as PFMOAA remains limited.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Assessment of Exposure Pathways for Perfluoroalkyl Ether Carboxylic Acids (PFECAs) in Residents Near a Fluorochemical Industrial Park: The Unanticipated Role of Cereal Consumption

Dong,

Pan,

Zhang

et al. 2023

Environ. Sci. Technol.

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Drinking Water–Associated PFAS and Fluoroethers and Lipid Outcomes in the GenX Exposure Study

Cited by 34 publications

References 42 publications

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

Comprehensive Assessment of Exposure Pathways for Perfluoroalkyl Ether Carboxylic Acids (PFECAs) in Residents Near a Fluorochemical Industrial Park: The Unanticipated Role of Cereal Consumption

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