Fluorinated alkyl substances and technical mixtures used in food paper‐packaging exhibit endocrine‐related activity in vitro

Rosenmai, Anna Kjerstine; Taxvig, Camilla; Svingen, Terje; Trier, Xenia; Vugt-Lussenburg, Barbara M.A. van; Pedersen, Michael; Lesné, Laurianne; Jégou, Bernard; Vinggaard, Anne Marie

doi:10.1111/andr.12190

Cited by 79 publications

(58 citation statements)

References 62 publications

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“…It was reported that exposure of MCF‐7 cells to 6:2 FTOH (30 μM) and 8:2 FTOH (10 μM) caused increases in S phase . This discrepancy may be owing to estrogenic activity of FTOHs in MCF‐7 cells . Cylins and cylin‐dependent kinases (CDKs) play a pivotal role in cell cycle progression.…”

Section: Discussionmentioning

confidence: 99%

8:2 Fluorotelomer alcohol causes G1 cell cycle arrest and blocks granulocytic differentiation in HL‐60 cells

Wang

Zhou

et al. 2019

Environmental Toxicology

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Fluorotelomer alcohols (FTOHs) are fluorinated intermediates used in manufacturing specialty polymer and surfactants, with 8:2 FTOH the homologue of largest production. FTOHs were found to pose acute toxicity, hepatotoxicity, nephrotoxicity, developmental toxicity and endocrine-disrupting risks, whereas research regarding immunotoxicity and its underlying mechanism, especially on specific immune cells is limited. Here, we investigated the immunotoxicity of 8:2 FTOH on immature immune cells in an in vitro system. We observed that exposure of HL-60 cells, a human promyelocytic leukemic cell line, to 8:2 FTOH reduced cell viability in a dose-and time-dependent manner. In addition, 8:2 FTOH exposure caused G1 cell cycle arrest in HL-60 cells, while it showed no effect on apoptosis. Exposure to 8:2 FTOH inhibited the mRNA expression of cell cycle-related genes, including CCNA1, CCNA2, CCND1, and CCNE2. Moreover, exposure to 8:2 FTOH inhibited the mRNA expression of granulocytic differentiation-related genes of CD11b, CSF3R, PU.1, and C/EPBε in HL-60 cells . Furthermore, 8:2 FTOH exhibited no effect on intracellular ROS level, while hydralazine hydrochloride (Hyd), one reactive carbonyl species (RCS) scavenger, partially blocked 8:2 FTOH-caused cytotoxicity in HL-60 cells. Overall, the results obtained in the study show that 8:2 FTOH poses immunotoxicity in immature immune cells and RCS may partially underline its mechanism. K E Y W O R D S 8:2 FTOH, cell cycle arrest, differentiation block, immature immune cells, immunotoxicity, reactive carbonyl species

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Section: Discussionmentioning

confidence: 99%

8:2 Fluorotelomer alcohol causes G1 cell cycle arrest and blocks granulocytic differentiation in HL‐60 cells

Wang

Zhou

et al. 2019

Environmental Toxicology

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“…Notably, two studies examined several PFAS chemicals used in food packing materials including fluorotelomer alcohols, 4:2 FTOH, 6:2 FTOH, 8:2 FTOH, and polyfluorinated alkyl phosphate esters, 8:2 monoPAP, 8:2 diPAP, 8:2 triPAP, 10:2 diPAP and reported increased estradiol, decreased testosterone production and estrogen receptor activation but no effect on PPARα or androgen receptor [184,185].…”

Section: Modulates Receptor-mediated Effectsmentioning

confidence: 99%

“…PFTrDA Association: [189] PFTeDA Association: [188]; [189]; [179] 8:2 FTOH Association: [184]; [185] No association: [188] 8:2 monoPAP Association: [184]; [185] 8:2 diPAP Association: [184] 8:2 triPAP Association: [184] 10:2 diPAP Association: [184] Short-chain PFAS b PFBS Association: [190] Association: [175]; [188]; [189]; [179]; [180] No association: [182] PFHxA…”

Section: Epidemiological Animal Biosassay In Vitromentioning

confidence: 99%

“…Association: [61] Association: [175]; [188]; [189]; [179]; [180] No association: [182] PFBA Association: [175]; [189]; [179]; [180] No association: [182] PFPeA Association: [179]; [180] PFHpA Association: [188]; [189]; [179]; [180] GenX (HFPO-DA); PMOH Association: [167]; [171] Association: [178] No association: [182] PMPP/ADONA No association: [182] 4:2 FTOH Association: [175]; [185] 6:2 FTOH Association: [175]; [185] No association: [188] a The following long-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFOSA. b The following short-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: 4:2 diPAP, 6:2 diPAP.…”

Section: Epidemiological Animal Biosassay In Vitromentioning

confidence: 99%

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Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

Temkin

Hocevar

Andrews

et al. 2020

IJERPH

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Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.

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“…These uses are described in industry patents and commercial materials 54 , but the levels and types of PFASs have been studied only to a limited extent 58,59 .…”

Section: Durable Water and Stain Repellency In Textilesmentioning

confidence: 99%

The Concept of Essential Use for Determining When Uses of PFASs Can Be Phased Out

Cousins

Goldenman²,

Herzke³

et al. 2019

Preprint

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Because of the extreme persistence of per- and polyfluoroalkyl substances (PFASs) and their associated risks, the Madrid Statement argues for stopping their use where they are deemed not essential or when safer alternatives exist. To determine when uses of PFASs have an essential function in modern society, and when they do not, is not an easy task. Here, we: 1) develop the concept of “essential use” based on an existing approach described in the Montreal Protocol, 2) apply the concept to various uses of PFASs to determine the feasibility of elimination or substitution of PFASs in each use category, and 3) outline the challenges for phasing out uses of PFASs in society. In brief, we developed three distinct categories to describe the different levels of essentiality of individual uses. A phase-out of many uses of PFASs can be implemented because they are not necessary for the betterment of society in terms of health and safety, or because functional alternatives are currently available that can be substituted into these products or applications. Some specific uses of PFASs would be considered essential because they provide for vital functions and are currently without established alternatives. However, this essentiality should not be considered as permanent; rather, constant efforts are needed to search for alternatives. We provide a detailed description of several ongoing uses of PFASs and discuss whether these uses are essential or nonessential according to the three essentiality categories. We suggest applying this concept of essential uses to all uses of PFASs, and considering its use also for other chemicals of concern.

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Fluorinated alkyl substances and technical mixtures used in food paper‐packaging exhibit endocrine‐related activity in vitro

Cited by 79 publications

References 62 publications

8:2 Fluorotelomer alcohol causes G1 cell cycle arrest and blocks granulocytic differentiation in HL‐60 cells

8:2 Fluorotelomer alcohol causes G1 cell cycle arrest and blocks granulocytic differentiation in HL‐60 cells

Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances

The Concept of Essential Use for Determining When Uses of PFASs Can Be Phased Out

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