Hexafluoropropylene Oxide Research Articles

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

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.

Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis

Initially considered a “safe” substitute for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been extensively used in the production of fluoropolymers for several years, leading to its environmental ubiquity and subsequent discovery of its significant bio-accumulative properties and toxicological effects. However, the specific impact of HFPO-TA on females, particularly those who are pregnant, remains unclear. In the present study, pregnant mice were exposed to 0.63 mg/kg/day HFPO-TA from gestational day (GD) 2 to GD 18. We then determined the potential effects of exposure on gut microbiota and fecal metabolites at GD 12 (mid-pregnancy) and GD 18 (late pregnancy). Our results revealed that, in addition to liver damage, HFPO-TA exposure during the specified window altered the structure and function of cecal gut microbiota. Notably, these changes showed the opposite trends at GD 12 and GD 18. Specifically, at GD 12, HFPO-TA exposure primarily resulted in the down-regulation of relative abundances within genera from the Bacteroidetes and Proteobacteria phyla, as well as associated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. With extended exposure time, the down-regulated genera within Proteobacteria became significantly up-regulated, accompanied by corresponding up-regulation of human disease- and inflammation-associated pathways, suggesting that HFPO-TA exposure can induce intestinal inflammation and elevate the risk of infection during late pregnancy. Pearson correlation analysis revealed that disturbances in the gut microbiota were accompanied by abnormal fecal metabolite. Additionally, alterations in hormones related to the steroid hormone biosynthesis pathway at both sacrifice time indicated that HFPO-TA exposure might change the steroid hormone level of pregnant mice, but need further study. In conclusion, this study provides new insights into the mechanisms underlying HFPO-TA-induced adverse effects and increases awareness of potential persistent health risks to pregnant females.

Emerging and legacy per- and polyfluoroalkyl substances in Daling River and its estuary, Northern China

Strict restriction on legacy per- and polyfluoroalkyl substances (PFASs) has caused a dramatic increase in production and usage of emerging PFASs over the last decades. However, the environmental behaviors of emerging PFASs is largely unknown in Daling River, Northern China. In this study, the potential sources, sediment-water partitioning and substitution trends of PFASs were investigated in overlying water and sediments from Daling River and its estuary. Perfluorooctane sulfonate and 6:2 fluorotelomer sulfonic acid were major compounds, and sodium p-perfluorous nonenoxybenzene sulfonate was first detected. Firefighting foam manufacturing and fluoropolymer production were the main sources of PFASs. Compared to legacy PFASs (C8), the emerging PFASs (C6 - C9) were more incline to distribute into overlying water. Substitution trends indicated 6:2 fluorotelomer sulfonic acid and hexafluoropropylene oxide trimer acid as the important alternatives of perfluorooctane sulfonate and perfluorooctanoic acid, respectively. The results were meaningful for understanding the environmental behaviors of emerging PFASs.

Adverse effects of gestational exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) homologs on maternal, fetal, and placental health in mice

In an effort to identify and develop potential alternatives for perfluorooctanoic acid (PFOA), PFDMO2HpA and PFDMO2OA have been engineered by reducing the -CF2 content in the molecular structure of hexafluoropropylene oxide trimer acid (HFPO-TA). Yet, despite their subsequent presence in environmental samples, there is a paucity of information regarding their toxicity, particularly on pregnancy. Here, pregnant CD-1 mice were exposed to PFDMO2HpA (0, 0.04, 0.16, 0.63, 2.5, or 10 mg/kg/day) or PFDMO2OA (0, 0.01, 0.04, 0.16, 0.63, or 2.5 mg/kg/day) via oral gavage from gestational days 2 (GD2) to 12 or 18 to evaluate the detrimental effects on dams and embryo-placenta units. Both two chemicals can transfer across the placenta, with a higher transfer ratio in late-pregnancy (GD18) than in mid-pregnancy (GD12), and PFDMO2OA being transferred at a higher rate than PFDMO2HpA. PFDMO2HpA/PFDMO2OA exposure caused maternal hepatotoxicity and fetal hepatomegaly, showing the lowest no-observed-adverse-effect level among all observed endpoints, which were used for calculating their reference dose (13.33 ng/kg/day). In the 2.5 and 10 mg/kg/day PFDMO2HpA groups as well as 2.5 mg/kg/day PFDMO2OA group at GD18, besides the abnormally high abortion rates exceeding 5 %, survival fetal weight was notably reduced (2.33 %, 6.44 %, and 5.59 % decrease relative to corresponding controls, respectively). Concurrently, placentas exhibited significant enlargement following PFDMO2HpA or PFDMO2OA exposure at doses of 0.63 mg/kg/day or higher, resulting in diminished placental efficiency. The deleterious effects of two chemicals on dams, fetuses, and placentas were stronger than that of PFOA or HFPO-DA, suggesting that neither PFDMO2HpA nor PFDMO2OA is suitable PFOA alternative. Bioinformatics analyses revealed significant alterations in the expression of genes involved in inflammation and immunity in the placenta upon exposure to 10 mg/kg/day PFDMO2HpA and 2.5 mg/kg/day PFDMO2OA at GD18, potentially elucidating mechanism behind the observed decrease in placental efficiency and increase in abortion rates after exposure.

GenX uptake by wheat and rice in flooded and non-flooded soils: a greenhouse experiment

GenX (hexafluoropropylene oxide dimer acid) belongs to the group of per- and poly-fluoroalkyl substance (PFAS) compounds introduced to replace perfluorooctanoic acid (PFOA), which has been phased out in industrial and consumer product formulations. While GenX has been investigated in lab animals, there is limited information available regarding its uptake and translocation in wheat and rice. This study reports on a greenhouse experiment in which wheat and rice grown under flooded and non-flooded conditions were exposed to two GenX concentrations in the soil (0.4 mg kg−1 and 2 mg kg−1). GenX was analysed in the soil, porewater and shoots using targeted liquid chromatography-tandem mass spectroscopy (LC-MS/MS) analysis. Extractable organic fluorine (EOF) was determined using high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-GFMAS) instrument. Results showed that different species took up different amounts of GenX. The GenX concentration in rice shoots was found to be 2.34 (± 0.45) and 4.11 (± 0.87) μg g−1 under flooded and non-flooded conditions, respectively, at a low exposure level. At high exposure, the GenX concentrations in flooded and non-flooded rice shoots increased threefold to 10.4 (± 0.41) and 13.4 (± 0.72) μg g−1, respectively. Wheat shoots showed similar concentrations and increases between low- and high-level exposure. The translocation factor was significantly higher (P = 0.013) in non-flooded rice compared to flooded rice. The GenX bioaccumulation behaviours under the same culture conditions (e.g. temperature, humidity, light, same GenX concentration in the soil) were significantly different in non-flooded and flooded rice (P < 0.001). Non-flooded rice plants displayed a higher level of GenX bioaccumulation than flooded ones. Following exposure to GenX, flooded rice plants showed a reduction in biomass (25%) compared to the control plants (P < 0.014). Our findings indicate that GenX is a bioaccumulative compound, the presence of which likely inhibits the growth of plants.

Legacy and alternative per-and polyfluoroalkyl substances (PFASs) in the Bohai Bay Rim: Occurrence, partitioning behavior, risk assessment, and emission scenario analysis

The use of alternative per- and polyfluoroalkyl substances (PFASs) has been practiced because of the restrictions on legacy PFASs. However, knowledge gaps exist on the ecological risks of alternatives and relationships between restrictions and emissions. This study systematically analyzed the occurrence characteristics, water-sediment partitioning behaviors, ecological risks, and emissions of legacy and alternative PFASs in the Bohai Bay Rim (BBR). The mean concentration of total PFASs was 46.105 ng/L in surface water and 6.125 ng/g dry weight (dw) in sediments. As an alternative for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (GenX) had a concentration second only to PFOA in surface water. In sediments, perfluorobutyric acid (PFBA) and GenX were the two predominant contaminants. In the water-sediment partitioning system, GenX, 9-chlorohexadecafluoro-3-oxanone-1-sulfonic acid (F-53B), and 11-chloroeicosafluoro-3-oxaundecane-1-sulfonic acid (8:2 Cl-PFESA) tended to be enriched towards sediments. The species sensitivity distribution (SSD) models revealed the low ecological risks of PFASs and their alternatives in the BBR. Moreover, predicted no-effected concentrations (PNECs) indicated that short-chain alternatives like PFBA and perfluorobutane sulfonate (PFBS) were safer for aquatic ecosystems, while caution should be exercised when using GenX and F-53B. Due to the incremental replacement of PFOA by GenX, cumulative emissions of 1317.96 kg PFOA and 667.22 kg GenX were estimated during 2004–2022, in which PFOA emissions were reduced by 59.2 % due to restrictions implemented since 2016. If more stringent restrictions are implemented from 2023 to 2030, PFOA emissions will further decrease by 85.0 %, but GenX emissions will increase by an additional 21.3 %. Simultaneously, GenX concentrations in surface water are forecasted to surge by 2.02 to 2.45 times in 2023. This study deepens the understanding of PFAS alternatives and assists authorities in developing policies to administer PFAS alternatives.

Differential Developmental Neurotoxicity and Tissue Uptake of the Per- and Polyfluoroalkyl Substance Alternatives, GenX and PFBS.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals with several applications. Multiple adverse health effects are reported for longer carbon chain (≤C8) PFAS. Shorter carbon chain PFAS, [e.g., hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) and perfluorobutanesulfonic acid (PFBS)] were introduced as alternatives. Past studies indicate that longer-chain PFAS are neurotoxic targeting the dopamine pathway, but it is not known if shorter-chain PFAS act similarly. This study aimed to evaluate developmental neurotoxicity and tissue uptake of GenX and PFBS using the zebrafish (Danio rerio). First, acute toxicity was assessed by measuring LC50 at 120 h postfertilization (hpf). Body burden was determined after embryonic exposure (1-72 hpf) to sublethal concentrations of GenX or PFBS by LC-ESI-MS/MS. Locomotor activity using a visual motor response assay at 120 hpf and dopamine levels at 72 hpf was assessed after embryonic exposure. PFBS was more acutely toxic and bioaccumulative than GenX. GenX and PFBS caused hyperactivity at 120 hpf, but stronger behavioral alterations were observed for PFBS. An increase in whole organism dopamine occurred at 40 ppb of GenX, while a decrease was observed at 400 ppb of PFBS. Differences detected in dopamine for these two PFAS indicate differential mechanisms of developmental neurotoxicity.

Kinetics and proposed mechanisms of hexafluoropropylene oxide dimer acid (GenX) degradation via vacuum-UV (VUV) photolysis and VUV/sulfite processes

We investigated the degradation of hexafluoropropylene oxide dimer acid (GenX) in water via VUV photolysis and VUV/sulfite reactions under nitrogen-saturated conditions. Approximately 35% and 90% of GenX were degraded in 3 h in the VUV photolysis and VUV/sulfite reaction. While GenX removal rate was highest at pH 6 in VUV photolysis, it increased under alkaline pHs, especially at pH 10, in VUV/sulfite reaction. Radical scavenging experiments showed that, while both eaq- and •H contributed to VUV photolysis, eaq- played a significant role and •OH had a negative effect during VUV/sulfite reaction. Two transformation products (TPs) (TFA and PFPrA) were identified in VUV photolysis, whereas five TPs (TFA, PFPrA, TP182, TP348, and TP366) were identified in VUV/sulfite reaction by LCMS/MS and LCQTOF/MS. Defluorination of GenX was observed with the defluorination efficiency after 6 h reaching 17% and 67% in the VUV photolysis and VUV/sulfite reactions, respectively. Degradation mechanism for GenX based on the identified TPs and the theoretical calculation confirmed the susceptibility of GenX to nucleophilic attack. The initial reactions for GenX decomposition were C–C and C–O bond cleavage in both reactions, whereas sulfonation followed by decarboxylation was observed only in the VUV/sulfite reaction. ECOSAR ecotoxicity simulation showed that the toxicities of the TPs were not as harmful as those of GenX.

Removal of per- and polyfluoroalkyl substances by activated hydrochar derived from food waste: Sorption performance and desorption hysteresis

Carbonaceous materials, derived from waste biomass, have proven to be a viable and appealing alternative for removing emerging micro-pollutants, such as per- and polyfluoroalkyl substances (PFAS). To assess the feasibility and efficacy of using material derived from food waste to alleviate PFAS pollution, this study prepared activated hydrochar (AHC) for sorbing ten PFAS, including five perfluoroalkyl carboxylic acids (PFCA; C4–C8), three perfluoroalkyl sulfonic acids (PFSA; C4, C6, C8), and two emerging PFAS, namely hexafluoropropylene oxide dimer acid (commercial name GenX, an alternative to perfluorooctanoic acid (PFOA)) and 6:2 fluorotelomer sulfonic acid (6:2 FTS). The results demonstrated that AHC possessed a relatively high specific surface area (207 m2/g) and hydrophobic surface properties. At environmentally relevant concentrations (40 μg/L), the sorption partition coefficients (log Kd) of PFAS on AHC ranged from 2.33 to 6.49 L/kg. Notably, GenX exhibited a lower log Kd value (2.33 L/kg) than PFOA (3.88 L/kg). The AHC showed favorable sorption performance for all tested PFAS, with log Kd values surpassing other reported sorbents (e.g., 0.83 for GenX on pyrochar, and 2.83 for PFOA on commercial biochar). Additionally, desorption hysteresis was observed for all PFAS, except for PFOA, and was particularly pronounced in PFBA, GenX, and 6:2 FTS at high initial concentrations, with Hysteresis Index (HI) values varying from 0.31 to 1.45, 0.68 to 1.88, and 0.51 to 1.85, respectively. Given its robust sorption capacity and desorption hysteresis toward PFAS, AHC is expected to be a favorable candidate for remediating PFAS-contaminated water. This study underscores, for the first time, the potential of food waste-derived hydrochar as an efficient sorbent for alleviating PFAS contamination, and further study is needed to investigate the sorption and desorption behaviors of PFAS on AHC at various environmental conditions.

Multiplicity-edited heteronuclear single quantum coherence experiment modified for 19F-13C

The popular multiplicity-edited heteronuclear single quantum coherence experiment has been modified for 19F-13C experiments by insertion of broadband inversion and refocusing pulses in 19F. This experiment has particular utility in distinguishing CF3 from CF2X, and CF2 from CFX (X = O or halide). Examples are shown of 1,1,2-trichloro-1,2,2-trifluoroethane, a mixture of 1,1,2-trichloro-1,2,2-trifluoroethane and two perfluoroolefins, and a mixture of poly(hexafluoropropylene oxide) and perfluorohexyl iodide. Phase distortions are minimized by careful selection of the value of JCF for which delays are optimized; a slight overstatement of JCF yielded no distortions, while an understatement did. Large 19F homonuclear couplings do not report cleanly in-phase. A one-dimensional version of the experiment yielded analogous editing by phase.

Binding interaction of environmental DNA with typical emerging perfluoroalkyl acids and its impact on bioavailability

As the replacement compounds of perfluoroalkyl acids (PFAAs), emerging PFAAs generally exhibit equal or more hazardous toxicity than legacy PFAAs. Numerous DNA as environmental organic matters coexists with emerging PFAAs, but their interactions and the resulting interaction impacts on the bioavailability of emerging PFAAs remain insufficiently understood. Here, we studied the binding strength and mechanism between DNA and emerging PFAAs (perfluorobutyric acid, perfluorobutylsulfonic acid, and hexafluoropropylene oxide dimer acid) using perfluorooctanoic acid as the control, and further investigated the impacts of DNA binding on the bioavailability of the emerging PFAAs. Isothermal titration calorimetry and quantum chemical calculation found that the emerging PFAAs could bind with DNA bases (main thymine) by van der Waals force and halogen-bond, showing the binding affinities in the range of 7.87 × 104 to L/mol to 6.54 × 106 L/mol. The PFAAs-DNA binding significantly decreased the bioavailability of the PFAAs in both seedlings and plants of pakchoi (Brassica chinensis L.), with little differences in bioavailability change extent among PFAAs. The findings highlight the universality and similarity of the DNA binding effects on PFAAs bioavailability, which can be the natural detoxification mechanism for response to the PFAAs pollution.

Different Life-Stage Exposure to Hexafluoropropylene Oxide Trimer Acid Induces Reproductive Toxicity in Adult Zebrafish (Danio rerio).

As a novel alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been widely used and has caused ubiquitous water pollution. However, its adverse effects on aquatic organisms are still not well known. In the present study, zebrafish at different life stages were exposed to 0, 5, 50, and 100 μg/L of HFPO-TA for 21 days to investigate reproductive toxicity in zebrafish. The results showed that HFPO-TA exposure significantly inhibited growth and induced reproductive toxicity in zebrafish, including a decrease of the condition factor, gonadosomatic index, and the average number of eggs. Histological section observation revealed that percentages of mature oocytes and spermatozoa were reduced, while those of primary oocytes and spermatocytes increased. In addition, exposure to HFPO-TA at three stages induced a significant decrease in the hatching rate, while the heart rate and normal growth rate of F1 offspring were only significantly inhibited for the exposure from fertilization to 21 days postfertilization (dpf). Compared with the exposure from 42 to 63 dpf, the reproductive toxicity induced by HFPO-TA was more significant for the exposure from fertilization to 21 dpf and from 21 to 42 dpf. Expression of the genes for cytochrome P450 A1A, vitellogenin 1, estrogen receptor alpha, and estrogen receptor 2b was significantly up-regulated in most cases after exposure to HFPO-TA, suggesting that HFPO-TA exhibited an estrogen effect similar to PFOA. Therefore, HFPO-TA might disturb the balance of sex steroid hormones and consequently induce reproductive toxicity in zebrafish. Taken together, the results demonstrate that exposure to HFPO-TA at different life stages could induce reproductive toxicity in zebrafish. However, the underlying mechanisms deserve further investigation. Environ Toxicol Chem 2023;42:2490-2500. © 2023 SETAC.

Hexafluoropropylene oxide trimer acid exposure triggers necroptosis and inflammation through the Wnt/β-catenin/NF-κB axis in the liver

Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging alternative to perfluorooctanoic acid (PFOA), has recently been identified as a significant environmental pollutant. Nevertheless, there is a scarcity of studies regarding the hepatotoxic effects of HFPO-TA. Here, we investigated the types and potential mechanisms of liver damage caused by HFPO-TA. Initially, we validated that the introduction of HFPO-TA resulted in the Wnt/β-catenin signaling (W/β signaling) activation, as well as the induction of necroptosis and inflammation, both in the liver of mice and in HepG2 cells. Subsequently, we established that the W/β signaling mediated the necroptosis and inflammation observed in the liver and HepG2 cells exposed to HFPO-TA. Finally, we demonstrated that the phosphorylated form of NF-κB p65 (p-NF-κB p65) played a role in mediating the necroptosis and inflammation, and its activity could be regulated by the W/β signaling pathway in the liver of mice and HepG2 cells exposed to HFPO-TA. In conclusion, our investigation elucidates the role of HFPO-TA in inducing necroptosis and inflammation in the liver, which is facilitated through the activation of the W/β/NF-κB axis.

Association of adverse fetal outcomes with placental inflammation after oral gestational exposure to hexafluoropropylene oxide dimer acid (GenX) in Sprague-Dawley rats

Hexafluoropropylene oxide dimer acid (HFPO-DA), known as “GenX” for its trade name, is gradually taking the place of Perfluorooctanoic acid (PFOA). However, there is a poor understanding of the developmental effects of GenX. This study aims to explore whether GenX produces adverse effects on offspring development in Sprague-Dawley (SD) rats and the underlying mechanisms. Pregnant rats were orally administered with GenX (0, 1, 10 and 100 mg/kg/day) from gestational 0.5–19.5 days. Experimental data showed that the exposure to GenX resulted in increased rats’ gestational weight gain, whereas both body weight and body length of their fetuses born naturally were significantly reduced. This could contribute to the developmental delays of fetal body weight, body length and tail length from postnatal 1–21 days. Histopathological evaluation of placenta indicated that GenX exposure led to neutrophil infiltration in decidual zone and congestion in labyrinth zone. Moreover, placental proteomics showed changes at the expression levels of the inflammation-related proteins in the Rap1 signaling pathway. In conclusion, gestational exposure to GenX induced fetal intrauterine and extrauterine development retardation in SD rats. Placental inflammation may play a key role in this process through the Rap1 signaling pathway.

Toxicity comparison of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (HFPO-DA), and hexafluoropropylene oxide trimer acid (HFPO-TA) in zebrafish gut

Hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA) are considered as alternatives to perfluorooctanoic acid (PFOA). In this study, zebrafish were exposed to different concentrations of PFOA, HFPO-DA, and HFPO-TA (5 μg/L and 500 μg/L), and the toxic effects on oxidative damage, inflammation, and cell apoptosis in the gut were compared. Additionally, changes in gut metabolome profiles and microbial community structure were analyzed. The results revealed that exposures to HFPO-DA and HFPO-TA led to lower levels of oxidative damage compared to PFOA exposure. However, all three treatments had comparable effects on inflammation and apoptosis. The main biological pathways affected by all three exposures were lipid metabolism, nucleotide metabolism, amino acid metabolism, and environmental information processing. The effects on metabolome profiles were much higher for HFPO-DA and HFPO-TA compared to PFOA at a concentration of 5 μg/L. At a concentration of 500 μg/L, HFPO-DA and HFPO-TA showed similar effects to PFOA. This study also examined the Pearson correlations between gut microbiota and the toxic effects mentioned above. The abundance of specific apoptosis-related genera differed among the three target chemicals, suggesting they may act differently in inducing apoptosis. The correlations between HFPO-DA and HFPO-TA were mostly similar, which helps explain the similar effects observed in their respective treatment groups on metabolic profiles. Overall, this study indicates that HFPO-DA and HFPO-TA may not be safe alternatives to PFOA and provides valuable insights into their toxic effects and risk assessment in water environments.

Activation of estrogen-related receptor: An alternative mechanism of hexafluoropropylene oxide homologs estrogenic effects

Perfluorooctanoic acid (PFOA) alternatives such as hexafluoropropylene oxide homologs (HFPOs) cause concern due to increased occurrence in the environment as well as potential bioaccumulation and toxicity. HFPOs have been demonstrated to activate the estrogen receptor (ER) pathway. The ER pathway is homologous and connected to the estrogen-related receptor (ERR) pathway, but HFPOs effects on the ERR pathway have not been studied. Hence, we assessed the potential estrogenic effects of HFPOs via ERRγ pathway. In vitro assays revealed that HFPO dimeric, trimeric, and tetrameric acids (HFPO-DA, −TA, and -TeA, respectively), acted as ERRγ agonists, activating the transcription of both human and zebrafish ERRγ at low concentrations, but inhibiting zebrafish ERRγ at high concentrations. We also found that HFPO-TA promoted the human endometrial cancer cells (Ishikawa cells) proliferation via ERRγ/EGF, Cyclin D1 pathway. The HFPO-TA-induced proliferation of Ishikawa cells was inhibited by co-exposure with a specific antagonist of ERRγ, GSK5182. In vivo exposure of female zebrafish to HFPO-TA disturbed sex hormone levels, interfered with the gene expression involved in estrogen synthesis and follicle regulation, and caused histopathological lesions in the ovaries, which were similar to those induced by a known ERRγ agonist GSK4716. Taken together, this study revealed a new mechanism concerning the estrogenic effect of HFPOs via activation of the ERRγ pathway.

New insights into the degradation mechanism and risk assessment of HFPO-DA by advanced oxidation processes based on activated persulfate in aqueous solutions

Hexafluoropropylene oxide dimer acid (HFPO-DA) is widely used as a substitute for perfluorooctanoic acid (PFOA). HFPO-DA exhibits high water solubility and low adsorption potential, conferring significant fluidity in aquatic environments. Given that the toxicity of HFPO-DA is similar to PFOA, it is necessary to control its content in aquatic environments. Electrochemical and thermally-activated persulfates have been successfully used to degrade HFPO-DA, but UV-activated persulfates cannot degrade the compound. Given that research on degradation mechanisms is still incomplete and lacks kinetic research, the mechanism and kinetic calculations of oxidative degradation were studied in detail using DFT calculations. And the toxicity of HFPO-DA degradation intermediates and products was evaluated to reveal the feasibility of using advanced oxidation process (AOP) technology based on persulfate to degrade HFPO-DA in wastewater. The results showed that the committed step of HFPO-DA degradation was initiated by the electron transfer reaction of SO4•- radicals. This reaction is not spontaneous at room temperature and requires sufficient electrical or thermal energy to be absorbed from the external environment. The perfluoroalcohol produced during this reaction can subsequently undergo four possible reactions: H atom abstraction from alcohol groups by an OH radical; H atom abstraction by SO4•-; direct HF removal; and HF removal with water as the catalyst. The final degradation products of HFPO-DA mainly include CO2, CF3CF2COOH, CF3COOH, FCOOH and HF, which has been identified through previous experimental analysis. Ecotoxicity assessment indicates that degradation does not produce highly toxic intermediates, and that the final products are non-toxic, supporting the feasibility of persulfate-based AOP technologies.

Influence of dietary bioactive compounds on the bioavailability and excretion of PFOA and its alternative HFPO-TA: Mechanism exploration

Oral ingestion is considered an important route of human exposure to perfluorooctanoic acid (PFOA) and its alternative hexafluoropropylene oxide trimer acid (HFPO-TA). Bioactive compounds are widely used as dietary supplements and food additives. However, little is known about the influence of dietary bioactive compounds on the bioavailability of PFOA and HFPO-TA. Here, three dietary bioactive compounds, β-carotene, quercetin and curcumin, were selected to study their influence on the relative bioavailability (RBA) of PFOA and HFPO-TA in soil using a mouse model. Compared to the control group (68.7 ± 6.27 %), quercetin and curcumin at medium and high doses (20 and 100 mg/kg/d) significantly (p < 0.05) decreased PFOA RBA to 55.2 ± 4.85–56.4 ± 4.57 % and 48.3 ± 5.49–48.6 ± 5.44 %, respectively. Mechanism study showed that medium- and high-dose quercetin as well as high-dose curcumin increased urinary excretion of PFOA by 33.6–35.6 % and 32.2 % through upregulating renal expression of multidrug resistance protein 2 (Mrp2) (1.52–1.63 folds) and Mrp4 (1.26–1.53 folds), thereby reducing PFOA accumulation. In PFOA-treated groups, quercetin at medium and high doses dramatically downregulated the hepatic expression of organic anion transport polypeptides (Oatp1a6, Oatp1b2), organic anion transport proteins (Oat1, Oat2), and fatty acid binding proteins (FABP4, FABP12), while curcumin at medium and high doses inhibited the hepatic expression of Oatp1a6, Oat1 and Oat2. These downregulated genes may reduce the transport of PFOA from blood to liver, and in turn decrease the PFOA RBA. However, β-carotene, quercetin and curcumin exhibited no significant effect on RBA and excretion of HFPO-TA (p > 0.05). This indicated the different absorption mechanisms between PFOA and HFPO-TA, and further research is warranted. This study provided a novel perspective for establishing environmentally friendly ways to reduce health hazards from per- and polyfluoroalkyl substances (PFASs).

New Insights into the Accumulation, Transport, and Distribution Mechanisms of Hexafluoropropylene Oxide Homologues, Important Alternatives to Perfluorooctanoic Acid, in Lettuce (Lactuca sativa L.).

Hexafluoropropylene oxide (HFPO) homologues, which are important alternatives to perfluorooctanoic acid, have been frequently identified in crops. Although exposure to HFPO homologues via crops may pose non-negligible threats to humans, their impact on crops is still unknown. In this study, the accumulation, transport, and distribution mechanisms of three HFPO homologues in lettuce were investigated at the plant, tissue, and cell levels. More specifically, HFPO trimer acid and HFPO tetramer acid were primarily fixed in roots and hardly transported to shoots (TF, 0.06-0.63). Conversely, HFPO dimer acid (HFPO-DA) tended to accumulate in lettuce shoots 2-264 times more than the other two homologues, thus resulting in higher estimated daily intake values. Furthermore, the dissolved organic matter derived from root exudate enhanced HFPO-DA uptake by increasing its desorption fractions in the rhizosphere. The transmembrane uptake of HFPO homologues was controlled by means of a transporter-mediated active process involving anion channels, with the uptake of HFPO-DA being additionally facilitated by aquaporins. The higher accumulation of HFPO-DA in shoots was attributed to the larger proportions of HFPO-DA in the soluble fraction (55-74%) and its higher abundance in both vascular tissues and xylem sap. Our findings expand the understanding of the fate of HFPO homologues in soil-crop systems and reveal the underlying mechanisms of the potential exposure risk to HFPO-DA.

PFAS soil concentrations surrounding a hazardous waste incinerator in East Liverpool, Ohio, an environmental justice community.

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic compounds widely used in industrial and consumer products. While PFAS provide product durability, these chemicals are ubiquitous, persistent, bioaccumulative, and toxic. These characteristics make the ultimate disposal of PFAS a challenge. One current disposal method is incineration; however, little research has been conducted on the safety and effectiveness of PFAS incineration. The characteristics of communities with hazardous waste incinerators that have received PFAS shipments indicate that more individuals with lower incomes and individuals with less education than the US average are at higher risk of exposure, which presents important environmental justice and health equity concerns of PFAS incineration. Situated in eastern Ohio, East Liverpool is an Appalachian community that is home to a large hazardous-waste incinerator, operated by Heritage WTI, that began accepting PFAS in 2019. Residents are concerned that the disposal lacks the research necessary to assure safety for the residents. Due to both community interest and data gaps regarding PFAS incineration, our research team conducted a pilot study to examine the distribution and concentration of PFAS in soil samples surrounding the incinerator. All 35 soil samples had measurable amounts of PFAS including perfluorobutanesulfonic acid (PFBS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide dimer acid (HFPO-DA)/GenX. PFOS was measured in the majority of soil samples (97%) with a range of 50-8,300ng/kg. PFOA was measured in 94% of soil samples with a range of 51ng/kg to 1300ng/kg. HFPO-DA/GenX was measurable in 12 soil samples with concentrations of ranging from 150ng/kg to 1500ng/kg. Further research on PFAS disposal will advance knowledge and action related to regulatory requirements and exposure prevention, ultimately improving individual and community protections and health equity.