ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2024
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IF 10.8
Jianglin Hu,Jiayin Dai,Nan Sheng
Following its introduction as an alternative to perfluorooctanoic acid, hexafluoropropylene oxide dimer acid (HFPO-DA) has been extensively detected in various environmental matrices. Despite this prevalence, limited information is available regarding its hepatotoxicity biomarkers. In this study, toxicokinetic simulations indicated that under repeated treatment, HFPO-DA in mice serum reached a steady state by the 4th day. To assess its subacute hepatic effects and identify potential biomarkers, mice were administered HFPO-DA orally at doses of 0, 0.1, 0.5, 2.5, 12.5, or 62.5 mg/kg/d for 7 d. Results revealed that the lowest observed adverse effect levels were 0.5 mg/kg/d for hepatomegaly and 2.5 mg/kg/d for hepatic injury. Serum metabolomics analysis identified 34, 58, and 118 differential metabolites in the 0.1, 0.5, and 2.5 mg/kg/d groups, respectively, compared to the control group. Based on weighted gene coexpression network analysis, eight potential hepatotoxicity-related metabolites were identified; among them, kynurenic acid (KA) in mouse serum exhibited the highest correlation with liver injury. Furthermore, liver-targeted metabolomics analysis demonstrated that HFPO-DA exposure induced metabolic migration of the kynurenine pathway from KA to nicotinamide adenine dinucleotide, resulting in the activation of endoplasmic reticulum stress and the nuclear factor kappa-B signaling pathway. Notably, pretreatment with KA significantly attenuated liver injury induced by HFPO-DA exposure in mice, highlighting the pivotal roles of KA in the hepatotoxicity of HFPO-DA.
研究领域:
毒理学
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环境科学
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代谢学
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分子生物学
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PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2023
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IF 13.6
Zhiwen Tang,Timothy M. Vogel,Qing Wang,Changlong Wei,Mukhtiar Ali,Xin Song
In this study, the biodegradability of trifluoroacetate (TFA), perfluorooctanoic acid (PFOA), and perfluoro-2-methyl-3-oxahexanoic acid (HFPO-DA) by a native microbial community was evaluated over a 10-month incubation period. The observed microbial defluorination ratios and removal efficiency were 3.46 ( ± 2.73) % and 8.03 ( ± 3.03) %, 8.44 ( ± 1.88) % and 13.52 ( ± 4.96) %, 3.02 ( ± 0.62) % and 5.45 ( ± 2.99) % for TFA, PFOA and HFPO-DA, respectively. The biodegradation intermediate products, TFA and pentafluoropropionic acid (PFA), of PFOA and HFPO-DA were detected in their biodegradation treatment groups. Furthermore, the concentrations of the PFOA metabolites, perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA), in the aqueous solutions after incubation were quantified to be 0.21 and 4.14 µg/L. TFA, PFOA and HFPO-DA significantly reduced the microbial diversity and changed the structure of the community. The co-occurrence network analysis showed that low abundance species, such as Flexilinea flocculi , Bacteriovorax stolpii , and g_Sphingomonas , are positively correlated with the generation of fluoride ion, implying their potential collaborative functions contributing to the observed biodefluorination. The findings in this study can provide insights for the biodegradation of perfluoroalkyl carboxylic acids and their emerging alternatives by indigenous microorganisms in the environment.
研究领域:
环境微生物学
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生物修复
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化学生态学
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PubMed
高影响因子
TOXICOLOGY
·
2026
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IF 5.2
Yiming Pang,Zhenzhong Wang,Yijun Liu,Chuanteng Feng,Yuchun Song,Shannan Cao,Dong Wang,Lianshuang Zhang,Peng Lu,Li Yu
Hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) is an environmentally persistent per- and polyfluoroalkyl substance (PFAS) alternative whose placental toxicity remains poorly understood. Pregnant Sprague-Dawley rats (n = 20, 5 dams/group) received oral HFPO-DA at 0, 1, 10, or 100 mg/kg·day from gestational day (GD) 0–19. Placental tissues collected on GD20 were analysed by targeted metabolomics, lipidomics, histopathology, immunohistochemistry (IHC), and immunofluorescence (IF). After false discovery rate (FDR) correction, three energy metabolites were significantly altered ( q < 0.05): oxaloacetate and glutamate were downregulated, while pyruvate was dose-dependently upregulated, consistent with restricted TCA cycle entry. Lipidomics identified 148 nominally significant lipid species, with elevated ceramides and long-chain fatty acids alongside reduced triglycerides, a pattern suggestive of impaired mitochondrial β-oxidation capacity. Histopathology revealed dose-dependent villous hyperplasia, trophoblast disorganization, and vascular lesions at the high dose. Protein analysis showed decreased SDHB, increased HIF-1α and PDK1, and a non-significant rise in PDHA1, collectively consistent with a shift toward Warburg-like metabolic reprogramming. These findings suggest that gestational HFPO-DA exposure may disrupt placental energy and lipid homeostasis at supra-environmental doses, identifying placental metabolism as a potentially sensitive target of next-generation PFAS.
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SEPARATION AND PURIFICATION TECHNOLOGY
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2025
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IF 9
Boxuan Yang,Yuxin Zeng,Tao Guo,Yuanzhong Lin,Lifeng Yin,Qingsong Hua
Hexafluoropropylene oxide dimer acid (HFPO-DA), an emerging persistent pollutant, has been prevalently utilized as an alternative to perfluorooctanoic acid (PFOA). Analogous to PFOA, HFPO − DA presents remarkable resistance against degradation by conventional technologies. In this study, we prepared Ce doped PbO 2 anode (Ce-PbO 2 ) and paired it with cathode to form redox system for the degradation of HFPO-DA in water. The results showed that the degradation rate of HFPO-DA over Ce-PbO 2 was as high as 1.67 × 10 −2 min −1 , much higher than that of Boron-doped diamond electrode (BDD, 6.84 × 10 –3 min −1 ). The Ce-PbO 2 anode also has the theoretical lifetime as high as 82.7 years. Free radical quenching experiments indicated that both reactive oxygen species (ROS) and reductive radicals contributed to the degradation of HFPO-DA. These degradation reactions start from a direct electron transfer, followed by electroreduction and a series of free radical reactions including decarboxylation, ether bond cleavage, and the “4A” processes (generation of Alkyl radicals, Alcohols, Acyl fluorides, and Acids in sequence) until it is decomposed into small molecules. Meanwhile, new intermediates (CF 3 CF 2 CF 2 OCF 3 CH•) generated by cathodic H• are dominating the reductive reaction during the electrochemical process. This “buttering bread on both sides” redox mechanism deepens the understanding of the degradation process of HFPO-DA and provides an efficient treatment strategy.
研究领域:
环境科学
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电化学
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污染治理
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
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IF 6.6
Fang Jia,Di Chen,Ziyuan Huang,Chengjie Wan,Ziyan Li,Tengchao Huang,Shuangqi Gao,Ying Guo
The incidence of acute ischemic stroke (AIS) has shown a persistent upward trend in recent years. External factors, including chemical and plastic exposures, have been shown to worsen the prognosis of cerebrovascular diseases, especially AIS. Hexafluoropropylene oxide dimer acid (HFPO-DA), a prevalent plastic additive, is globally distributed. However, its bioaccumulation potential and neurovascular toxicity remain poorly understood. Using a mixed subchronic-acute aggravation model in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, we found that HFPO-DA exposure dose-dependently exacerbated neurological deficits, enlarged infarct volumes, and intensified reactive microgliosis. Computationally, we prioritized the CSNK2A1/GSK3B/NF-κB signaling axis as a key mechanistic candidate, with bindings predicted by molecular docking. In vitro cellular thermal shift assays (CETSA) coupled with targeted siRNA knockdown in BV2 cells supported a direct physical interaction between HFPO-DA and CSNK2A1. Moreover, in vivo CSNK2A1 inhibition with CX-4945 partially reversed the HFPO-DA-induced aggravation of ischemic injury. Collectively, our results suggest that HFPO-DA might be a potent environmental driver of post-ischemic neuroinflammation, likely acting in part via the CSNK2A1/GSK3B/NF-κB signaling pathway. These results provide novel insights into the specific neurotoxic mechanisms of HFPO-DA, highlighting its potential health risks in susceptible populations.
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ENVIRONMENTAL GEOCHEMISTRY AND HEALTH
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2025
·Vol. 47
·期 7
·1-13
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IF 3.8
Shi Yanfeng,Han Xinle,Wu Lixingzi,Fu Ling,Xue Weina,Jing Xuli,Xu Jing,Zhang Zhibin,Ding Botao
Hexafluoropropylene oxide dimer acid (HFPO-DA, tradename Gen-X) is used as a substitute to perfluorooctanoic acid (PFOA). Its widespread presence in the environment and potential health risks on humans. Nevertheless, the research on transport of HFPO-DA in saturated porous media remains limited. This study investigates the effects of hydrochemical conditions on the transport behavior of HFPO-DA and PFOA in quartz sand and limestone porous media, such as ionic type (Na + , Ca 2+ ), ionic strength (1 mM, 10 mM, 50 mM) and initial solution pH (pH = 4, 7, 10). Findings indicate that both HFPO-DA and PFOA have high mobility in saturated media. The transport of HFPO-DA through quartz sand and limestone porous media is not notably influenced by different ionic types and strengths, with recoveries all over 98.94% and R f all below 1.02. Similarly, PFOA showed high mobility under different ionic conditions, with recoveries exceeding 101.68% and Rf less than 1.02.The influence of initial pH on the transport of HFPO-DA showed that HFPO-DA is pH-sensitive in quartz sand, with retention enhanced and significant trailing of the BTC at pH = 4; however, the pH-buffering capacity of limestone media reduced the impact of pH on HFPO-DA transportation. Compared with PFOA, HFPO-DA transported faster at pH = 4 with an R f value of 0.97, lower than that of PFOA at 1.21, due to its smaller molecular weight and shorter carbon chain. Overall, the research reveals the potent mobility of HFPO-DA and PFOA in the environment, highlighting their groundwater pollution potential and environmental risks.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
·
IF 6.8
Weiqiang Sun,Xuemin Zhang,Ying Qiao,Nathan Griffin,Hongxia Zhang,Li Wang,Hui Liu
Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC 50 (PFOA 100 μM, Gen-X 200 μM, HFPO-TA 30 μM). At the same LC 50 toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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高影响因子
Environmental Chemistry and Ecotoxicology
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2026
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IF 12.3
Yan Li,Zejun Ma,Xiaoxi Xia,Wanyu Wu,Yiwu Lai,Mallavarapu Megharaj,Xiangdong Han,Ziquan Wang,Wenxiang He
Background Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants of global concern. However, the soil ecotoxicity of emerging alternatives, such as hexafluoropropylene oxide dimer acid (HFPO-DA, a PFOA substitute), remains poorly understood. Objectives This study evaluated the ecotoxicological effects of a typical long-chain PFAS, perfluorooctanoic acid (PFOA), and its short-chain substitute, HFPO-DA, on diverse arylsulfatase (ARS) pools across eight soil types. The inhibitory mechanisms were further elucidated using integrated enzyme kinetics and molecular simulation approaches. Results The results showed that intracellular ARS (intra-ARS) dominated the total enzyme pool (54.44%–77.44%) and was positively correlated with microbial biomass carbon ( p < 0.05). The catalytic efficiency of intra-ARS was the most sensitive to PFAS exposure, with HFPO-DA exhibiting higher toxicity, as reflected by lower ED 10 values (the concentration causing a 10% reduction in intra-ARS catalytic efficiency), ranging from 2.06 to 36.33 mg kg −1 . Enzyme kinetics analyses indicated that both PFAS primarily caused competitive inhibition. Notably, HFPO-DA displayed a lower inhibition constant ( K ic ) than PFOA, suggesting a stronger binding affinity to the enzyme. Molecular docking further supported this finding, with binding energies of −5.8 and − 6.6 kcal mol −1 for PFOA and HFPO-DA, respectively, indicating that HFPO-DA forms a more stable complex with ARS. Principal Component Analysis (PCA) revealed that variability in the toxicity threshold (ED 10 ) was mainly driven by soil organic matter, total nitrogen, clay content, and pH. Based on these factors, a multivariate regression model was developed that accurately predicted toxicity thresholds (adjusted R 2 = 0.914 and 0.842), demonstrating strong predictive capability. Conclusion These findings provide a critical theoretical basis from the perspective of soil enzymatic function for establishing scientifically sound safety thresholds for PFAS across different soil types and for optimizing remediation strategies for contaminated soils.
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高影响因子
Toxics
·
2025
·Vol. 13
·期 10
·850
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IF 4.1
Jie Peng,Wei Jiang,Zi Long,Yueying Cui,Guizhen Zhu,Rui Liu,Deqin Kong,Weihua Yu,Yuliang Li,Chunxu Hai
Objective: Hexafluoropropylene oxide dimer acid (HFPO-DA), also known as GenX, is widely used globally, raising concerns about its safety and public health implications. However, its toxicity mechanism remains unclear. The purpose of this study was to develop a reliable method for detecting HFPO-DA in mice and to investigate its absorption, distribution, and impact on hepatic lipid metabolism. Method: HFPO-DA levels were measured in the serum and eight tissues of C57BL/6J mice after oral administration using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Lipid metabolites in the liver were also detected and analyzed. Results: HFPO-DA was rapidly absorbed into the bloodstream and widely distributed throughout all tested tissues. It penetrated the blood–brain barrier, with the highest concentration in the liver; however, long-term effects on the lungs also warrant attention. HFPO-DA disrupted liver lipid metabolism, leading to acylcarnitine accumulation while lowering triglycerides and cholesterol. Conclusion: This study on the pharmacokinetics and tissue distribution of HFPO-DA in mice following oral exposure revealed that HFPO-DA exacerbates liver injury by altering hepatic lipid metabolism. These findings provide theoretical support for toxicological studies on the emerging environmental pollutant HFPO-DA.
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Journal of Environmental Sciences
·
2024
·
IF 5.9
Shi-Ya Peng,Ya-Di Yang,Rong Tian,Naihao Lu
A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.
研究领域:
生物化学
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毒理学
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环境科学
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PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Dengdiao Yao,Jian Shao,Dantong Jia,Weiling Sun
Hexafluoropropylene oxide dimer acid (HFPO-DA) and perfluoroethylcyclohexane sulfonate (PFECHS) are increasingly used as alternatives for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, their immunotoxicity and underlying molecular mechanisms remain poorly understood. Here, to assess immunotoxic effects, zebrafish embryos were exposed to environmentally relevant concentrations of PFOA, PFOS, HFPO-DA, and PFECHS for four days. Results revealed that all four per- and polyfluoroalkyl substances (PFAS) resulted in decreased heart rate and spontaneous movement, and induced oxidative stress in zebrafish larvae. Notably, HFPO-DA exhibited more severe oxidative stress than PFOA. Immune dysfunction was observed, characterized by elevated cytokine, complement factor, nitric oxide, and neutrophil content, along with a significant decrease in lysozyme content. Transcriptomic analysis revealed the activation of Toll-like receptor (TLR)/NOD-like receptor (NLR)/RIG-I-like receptor (RLR) and associated downstream genes, indicating their pivotal role in PFAS-induced immunomodulation. Molecular docking simulations demonstrated stable interactions between PFAS and key receptors (TLR2, NOD2 and RIG-I). Overall, HFPO-DA and PFECHS exhibited immunotoxic effects in zebrafish larvae similar to legacy PFAS, providing important information for understanding the toxic mode of action of these emerging alternatives.
研究领域:
环境毒理学
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免疫学
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分子生物学
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PubMed
高影响因子
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