Search Results (246)

Per- and polyfluoroalkyl substances (PFAS) persist in soils, yet their effects on invertebrate immunity remain poorly understood. We compared a legacy congener, perfluorooctanoic acid (PFOA), with three short-chain ether acids GenX (C6), MOBA (C5), and MOPrA (C4) using a 72 h OECD-207 filter-paper assay in the earthworm Eisenia fetida. Endpoints spanned cellular and humoral defenses: amoebocyte morphometry, oxidative burst (ROS production), phenol oxidase (PO) activity, and the transcription of the lectin CCF-1 and the pore-forming protein lysenin. MOBA and MOPrA caused enlargement of amoebocytes, whereas PFOA and GenX had no morphometric impact. Oxidative burst fell significantly for all congeners. PO inhibition followed the same potency order (MOPrA > GenX > MOBA ≫ PFOA), with near-complete loss at 229 µM MOPrA. Gene expression assays for CCF-1 and lysenin showed shifts in relative fold change for each PFAS congener. The combined biomarker panel—amoebocyte size, ROS, CAT, PO, CCF-1, and lysenin—offers a concise framework for assessing terrestrial PFAS risk and guiding remediation monitoring. Full article

Perfluorinated alkyl substances and polyfluorinated alkyl substances (PFASs) are long-chain compounds, with perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) being the most well-known examples. Both are considered typical non-genotoxic carcinogens (NGTxCs). In this study, we verified whether the Bhas 42 cell transformation assay (Bhas 42 CTA) can be used as an effective in vitro method to predict carcinogenicity of NGTxCs using both PFOA and PFOS as typical representatives. Transcriptome analysis during the PFOA-induced transformation process showed that many factors related to the effects of PFOA on the immune system and cancer hallmarks increased or decreased. Thus, we demonstrated that mechanistic analyses such as transcriptome analyses in combination with the transformation focus formation results from the Bhas 42 CTA may be useful tools when assessing the carcinogenicity and other biological effects of NGTxCs such as PFOA. We propose that the Bhas 42 CTA is a simple in vitro test for the detection of NGTxCs, that it has in vitro oncotransformation as an endpoint, and that it can also detect the activation of factors involved in malignant progression, such as invasion and metastasis. It allows for the comprehensive detection of subtle mechanisms in parallel with focus formation throughout the transformation process, from the early stages to malignancy. Full article

Per- and polyfluoroalkyl substances (PFASs) are highly chemically stable synthetic compounds. They are widely used in industrial and commercial sectors due to their ability to repel water and oil, thermal stability, and surfactant properties. However, this stability results in environmental persistence and bioaccumulation, posing significant health risks as PFASs eventually find their way into environmental media. Key PFAS compounds, including PerFluoroOctanoic Acid (PFOA), PerFluoroOctane Sulfonic acid (PFOS), and PerFluoroHexane Sulfonic acid (PFHxS), have been linked to hepatotoxicity, immunotoxicity, neurotoxicity, and endocrine disruption. In response to the health threats these substances pose, global regulatory measures, such as the Stockholm Convention restrictions and national drinking water standards, have been implemented to reduce PFAS exposure. Despite these efforts, a lack of universally accepted definitions or comprehensive inventories of PFAS compounds hampers the effective management of these substances. As definitions differ across regulatory bodies, research and policy integration have become complicated. PFASs are broadly categorized as either perfluoroalkyl acids (PFAAs), precursors, or other fluorinated substances; however, PFASs encompass over 5000 distinct compounds, many of which are poorly characterized. PFAS contamination arises from direct industrial emissions and indirect environmental formation, these substances have been detected in water, soil, and even air samples from all over the globe, including from remote regions like Antarctica. Analytical methods, such as primarily liquid and gas chromatography coupled with tandem mass spectrometry, have advanced PFAS detection. However, standardized monitoring protocols remain inadequate. Future management requires unified definitions, expanded monitoring efforts, and standardized methodologies to address the persistent environmental and health impacts of PFAS. This review underscores the need for improved regulatory frameworks and further research. Full article

This study investigated the occurrence, sources, and health risks of 21 per- and polyfluoroalkyl substances (PFAS) in commercially available shellfish and crustaceans from Zhejiang Province, China. Among the 306 samples analyzed, 87.9% contained at least one detectable PFAS. Perfluorooctanoic acid (PFOA) was the most frequently detected PFAS (64.7%), followed by perfluorooctanesulfonic acid (PFOS) (53.8%), perfluorononanoic acid (PFNA) (52.9%), and perfluorodecanoic acid (PFDA) (50.0%). The total PFAS in shellfish and crustaceans ranged from ND to 0.86 to 173 ng/g wet weight, with a median of 4.11 ng/g ww; the median concentration of total PFAS followed this order: marine crustaceans > fresh-water crustaceans > bivalves. Estimation of the human intake of adult consumers, the estimated daily intake (EDI) of Σ₂₁ PFAS ranged from 0.01 to 15.7 ng/kg bw/day; 0.31% of the adult study population had Σ₄PFAS exposure levels resulting in Hazard Quotient (HQ) values > 1, which may represent a potential public health concern for these individuals. Long-term exposure risks for specific PFCAs such as perfluoroundecanoic acid (PFUdA) and perfluorotridecanoic acid (PFTrDA) merit concern. Full article

Per- and polyfluoroalkyl substances (PFASs), called forever chemicals, persist in the environment and bioaccumulate, posing significant health risks. While epidemiological studies have linked exposure to specific PFAS types, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), to an increased incidence of various cancers, specific tumorigenesis mechanisms are unknown. Here, we investigated the potential molecular markers and signatures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) tumorigenesis. We performed a comprehensive transcriptomic analysis across multiple species and tissue types (N = 529) using PFOS and PFOA-exposed RNA-Seq samples. Conserved signatures demonstrate significant disruptions in seven key carcinogenic characteristics including metabolic reprogramming, epigenetic modifications, immune suppression, oxidative stress, and genomic instability. Tumorigenic markers such as SERPINE1, FN1, PLIN2, ALDOA, TRIB3, and TSC22D3 and their associated pathways may act independently or synergistically to promote a pro-tumorigenic environment. Additionally, PPARα, LARP1, ACOX1, MYC, and MYCN were identified as key upstream regulators supporting disruptions in lipid metabolism, oxidative stress, and uncontrolled cell proliferation. In liver samples, low concentrations of PFOS and PFOA were sufficient to exhibit tumorigenic signatures associated with tumorigenesis initiation and development. Inferred mechanisms of ccRCC initiation and development were linked to lipid metabolism dysregulation and immunosuppressive signaling. In prostate and testicular xenograft tumor models, carcinogenic mechanisms for tumor progression and promotion were hypothesized. Receptor-mediated signaling and protein synthesis was disrupted in prostate cancer and epigenetic alterations and ECM remodeling observed in testicular cancer. We also explored potential therapeutic rescue strategies, including chemopreventive agents for early intervention. All our findings provide hypotheses for PFOS/PFOA-induced tumorigenesis; however, experimental studies are required to establish translational relevance. All the R codes developed in this study are publicly available. Full article

Environmental pollution by poly- and perfluoroalkyl substances (PFAS) can impact human health through drinking water and the ingestion of contaminated agri-food. Plants can take up PFAS from polluted soils or irrigation waters, and soil amended with biochar has been proposed as a practical and sustainable option to effectively reduce the PFAS transfer from soils to plants. We evaluated the potential of biochar, the byproduct of biomass pyrolysis, to reduce or prevent PFAS uptake from contaminated soil and water in a field trial conducted in a PFAS-contaminated area, where tomato and red chicory plants were grown in succession. The PFAS content in irrigation water, soil, and tomato and red chicory plants was determined by liquid chromatography coupled to mass spectrometry before and after each cultivation trial. Compared to those grown in unamended soil, tomato plants grown in the biochar-amended soil showed a significantly lower uptake of perfluorobutane sulfonic acid (PFBS), perfluoroheptanoic acid (PFHpA), and perfluorooctanoic acid (PFOA) in the leaves (−70%, −45%, and −84%, respectively), and significantly less (−61%) perfluorobutanoic acid (PFBA) in the fruits. Compared to unamended soils, leaves of red chicory plants grown in biochar-amended soil accumulated less PFBS (−74%) in the early growth stage and less PFBA (−34%) at plant maturity. The presented results confirmed previous reports on the potential soil amendment with biochar as a sustainable and effective measure for reducing PFAS uptake by horticultural crops cultivated in PFAS-polluted areas and PFAS concentration in their edible parts. Implications of this approach are also discussed. Full article

Micro(nano)plastics are important emerging contaminants and a current research hotspot in the environmental field. Micro(nano)plastics widely exist in various organic wastes such as waste sludge, food waste (FW) and livestock manure and often enter into digesters along with anaerobic digestion (AD) treatment of these wastes, thereby exerting extensive and profound influences on anaerobic process performance. This study reviews sources of micro(nano)plastics and their pathways entering the anaerobic system and summarizes the quantities, sizes, shapes and micromorphology of various micro(nano)plastics in waste sludge, FW, livestock manure, yard waste and municipal solid waste. The current advances on the effects of multiple micro(nano)plastics mainly polyvinyl chloride (PVC), polystyrene (PS) and polyethylene (PE) with different sizes and quantities (or concentrations) on AD of organic wastes in terms of methane production, organic acid degradation and process stability are comprehensively overviewed and mechanisms of micro(nano)plastics affecting AD involved in microbial cells, key enzymes, microbial communities and antibiotic resistance genes are analyzed. Meanwhile, coupling effects of micro(nano)plastics with some typical pollutants such as antibiotics and heavy metals on AD are also reviewed. Due to the extreme complexity of the anaerobic system, current research still lacks full understanding concerning composite influences of different types, sizes and concentrations of micro(nano)plastics on AD under various operating modes. Future research should focus on elucidating mechanisms of micro(nano)plastics affecting organic metabolic pathways and the expression of specific functional genes of microorganisms, exploring the fate and transformation of micro(nano)plastics along waste streams including but not limited to AD, investigating the interaction between micro(nano)plastics and other emerging contaminants (such as perfluorooctanoic acid and perfluorooctane sulphonate) and their coupling effects on anaerobic systems, and developing accurate detection and quantification methods for micro(nano)plastics and technologies for eliminating the negative impacts of micro(nano)plastics on AD. Full article

Interactions between protamines and DNA are essential for the correct structure of human sperm chromatin. Reproductive health can be adversely affected by environmental pollutants like per- and polyfluoroalkyl substances (PFAS). We previously reported that exposure to PFAS in the Veneto region causes alterations in sperm nuclear basic proteins (SNBP), along with reduced seminal antioxidant activity and increased lipoperoxides. This study analysed the protamine-to-histone ratio in SNBP and quantified the extent of DNA damage induced by SNBP in subjects in Veneto with serum perfluorooctanoic acid (PFOA) levels above the reference threshold. We found that all individuals with serum PFOA above the threshold exhibited grade three DNA damage, regardless of the protamine–histone ratio, which was generally altered but consistently shifted toward protamines. This indicate that exposure to PFAS can alter the protamine–histone ratio in these subjects. Moreover, SNBPs from these individuals showed reduced DNA-protective capacity under pro-oxidant conditions, suggesting a role in oxidative damage. To rationalize these effects, in this cross sectional study, we investigated the potential interactions between PFAS and human protamines by molecular docking analyses which showed that PFAS can form stable complexes with DNA through hydrophobic and polar interactions, especially with thymine pyrimidine rings. Further, docking analyses revealed that fluorine atoms in PFAS may interact with guanidinium groups in protamine P1 via electrostatic and van der Waals forces, competing with DNA for binding sites and potentially disrupting chromatin organisation. A ternary PFAS–DNA–protamine adduct may underpin the observed DNA damage. These results suggest that PFAS induce oxidative stress, which could affect male fertility. Full article

This research letter reviews the recorded serum values obtained following the detection of perfluorooctanoic acid (PFOA) water contamination in Veneto, which are underestimations of the true extent of the internal contamination experienced by the exposed populations. The most likely peak serum concentrations were in a range with a median of 136.0 and an intequartile( IQR )of 64.8–258.3 ng/mL for young males and a median of 74.5 and an IQR of 22.6–167.4 ng/mL for young females, compared to the median serum PFOA contamination that was finally detected (64.1 for males and 30.2 ng/mL for females, respectively) when blood samples were drawn. This was 27 months after the implementation of the single granular activated carbon drinking water filtration and 30 months after the disclosure of the heavy drinking water contamination. Full article

Purpose: Per- and polyfluoroalkyl substances (PFAS) comprise a class of man-made compounds widely utilized in manufacturing everyday consumer products. Experimental studies indicate that PFAS may interfere with iron regulation by hindering absorption or inducing oxidative stress. Nonetheless, epidemiological studies examining the association between PFAS exposure and a broad spectrum of iron-related biomarkers remain scarce. Approach and Results: In this study, data from the 2013–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed, which included 5050 adults aged 18 and older. The relationships between six PFAS compounds, oral iron intake, and a comprehensive set of markers of iron homeostasis, including serum iron, unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), transferrin saturation, ferritin, and transferrin receptor levels, were examined. Our findings revealed a negative association between both individual and total PFAS (sum of six PFAS) levels and oral iron intake. Additionally, serum iron and transferrin saturation levels exhibited significant positive correlations with all PFAS compounds, whereas ferritin was positively correlated with all PFAS compounds except n-perfluorooctanoic acid (n-PFOA). UIBC and transferrin receptor showed significant negative correlations with all PFAS compounds, while TIBC was significantly negatively correlated with n-perfluorooctane sulfonic acid (n-PFOS), perfluoromethylheptane sulfonic acid isomers (sm-PFOS), perfluorohexane sulfonic acid (PFHxS), and the total PFAS. Conclusions: Higher PFAS exposure was associated with altered iron status biomarkers While this cross-sectional study cannot establish causality, the observed associations raise the possibility that PFAS exposure may influence iron absorption. These findings emphasize the need for additional research into the potential impact of PFAS exposure on iron homeostasis. Full article

Per- and polyfluoroalkyl substances (PFASs) have gained significant attention due to their widespread distribution in the environment and potential adverse health effects. While ingestion, especially through contaminated drinking water, is considered the primary route of human exposure, recent research suggests that other pathways, such as inhalation and dermal absorption, also play a significant role. This review provides a concise overview of the toxicological impacts of both legacy and emerging PFASs, such as GenX and perfluorobutane sulfonic acid (PFBS), with a particular focus on their effects on the liver, kidneys, and immune and nervous systems, based on findings from recent in vivo, in vitro, and epidemiological studies. Despite the transition to PFAS alternatives, much of the existing toxicity data focus on a few legacy compounds, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which have been linked to adverse immune outcomes, particularly in children. However, evidence for carcinogenic risk remains limited to populations with extremely high exposure levels, and data on neurodevelopmental effects remain underexplored. While epidemiological and experimental animal studies supported these findings, significant knowledge gaps persist, especially regarding emerging PFASs. Therefore, this review examines the visceral, neural, and immunotoxicity data for emerging PFASs and mixtures from recent studies. Given the known risks from well-studied PFASs, a precautionary principle should be adopted to mitigate human health risks posed by this large and diverse group of chemicals. Full article

Per- and polyfluoroalkyl substances (PFASs) are emerging pollutants of global concern due to their high environmental persistence and bioaccumulative characteristics. This study investigates PFAS concentrations in soils from China through an extensive literature review, covering soil samples from seventeen provinces and the years from 2009 to 2024. It was found that the total concentration of PFAS in soil ranged from 0.25 to 6240 ng/g, with the highest contamination levels observed in coastal provinces, particularly Fujian (620 ng/g) and Guangdong (1090 ng/g). Moreover, Fujian Province ranked the highest among multiple regions with a median PFAS concentration of 15.7 ng/g for individual compounds. Ecological risk assessment, focusing on areas where perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) were identified as the primary soil PFAS compounds, showed moderate ecological risk from PFOA in Shanghai (0.24), while PFOS posed a high ecological risk in Fujian and Guangdong, with risk values of 43.3 and 1.4, respectively. Source analysis revealed that anthropogenic activities, including PFAS production, firefighting foam usage, and landfills, were the primary contributors to soil contamination. Moreover, soil PFASs tend to migrate into groundwater via adsorption and seepage, ultimately entering the human body through bioaccumulation or drinking water, posing health risks. These findings enhance our understanding of PFAS distribution and associated risks in Chinese soils, providing crucial insights for pollution management, source identification, and regulation strategies in diverse areas. Full article

Background: Environmental exposures, such as per- and polyfluoroalkyl substances (PFAS), in conjunction with social and behavioral factors, can significantly impact liver health. This research investigates the combined effects of PFAS (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), alcohol consumption, smoking, income, and education on liver function among the U.S. population, utilizing data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Methods: PFAS concentrations in blood samples were analyzed using online solid-phase extraction combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS), a highly sensitive and specific method for detecting levels of PFAS. Liver function was evaluated using biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin, and the fatty liver index (FLI). Descriptive statistics and multivariable linear regression analyses were employed to assess the associations between exposures and liver outcomes. Bayesian Kernel Machine Regression (BKMR) was utilized to explore the nonlinear and interactive effects of these exposures. To determine the relative influence of each factor on liver health, Posterior Inclusion Probabilities (PIPs) were calculated. Results: Linear regression analyses indicated that income and education were inversely associated with several liver injury biomarkers, while alcohol use and smoking demonstrated stronger and more consistent associations. Bayesian Kernel Machine Regression (BKMR) further highlighted alcohol and smoking as the most influential predictors, particularly for GGT and total bilirubin, with posterior inclusion probabilities (PIPs) close to 1.0. In contrast, PFAS showed weaker associations. Regression coefficients were small and largely non-significant, and PIPs were comparatively lower across most liver outcomes. Notably, education had a higher PIP for ALT and GGT than PFAS, suggesting a more protective role in liver health. People with higher education levels tend to live healthier lifestyles, have better access to healthcare, and are generally more aware of health risks. These factors can all help reduce the risk of liver problems. Overall mixture effects demonstrated nonlinear trends, including U-shaped relationships for ALT and GGT, and inverse associations for AST, FLI, and ALP. Conclusion: These findings underscore the importance of considering both environmental and social–behavioral determinants in liver health. While PFAS exposures remain a long-term concern, modifiable lifestyle and structural factors, particularly alcohol, smoking, income, and education, exert more immediate and pronounced effects on hepatic biomarkers in the general population. Full article

Perfluorooctanoic acid (PFOA) and its replacement, GenX, are per- and polyfluoroalkyl substances (PFASs) widely used in industrial and consumer applications. Pregnant women are a vulnerable population to environmental pollutants. The maternal effects of GenX and PFOA exposure during pregnancy have not been fully elucidated. In this study, pregnant mice received daily oral doses of GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water (control) throughout gestation. Histopathological analyses revealed significant liver abnormalities in both exposure groups, including hepatocyte swelling, cellular disarray, eosinophilic degeneration, karyopyknosis, lipid vacuolation, and increased inflammatory responses. Through transcriptomics analyses, it was found that multiple metabolic and inflammatory pathways were enriched in both exposure groups. In the GenX group, overexpression of CYP4A, c-Myc, and Oatp2 proteins and decreased expression of EGFR and β-catenin in the liver suggested disruption of lipid and bile acid metabolism. In the PFOA group, significantly upregulated protein levels of NLRP3, GSDMD, caspase-1, IL-18, and IL-1β indicated hepatic pyroptosis. Despite these distinct pathways, both compounds triggered inflammatory cytokine release in the liver, consistent with the results of the transcriptomics analysis, suggesting shared mechanisms of inflammatory liver injury. Taken together, our findings provided novel insights into the hepatotoxicity mechanisms of GenX and PFOA exposure during pregnancy, underscoring the potential health risks associated with PFAS exposure. Full article

Background: Exposure to per- and polyfluoroalkyl substances (PFAS, including 7H-Perfluoro-4-methyl-3,6-dioxaoctanesulfonic acid (PFESA-BP2), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide (GenX), has been associated with liver dysfunction. While previous research has characterized PFAS-induced hepatic lipid alterations, their downstream effects on energy metabolism remain unclear. This study investigates metabolic alterations in the liver following PFAS exposure to identify mechanisms leading to hepatoxicity. Methods: We analyzed RNA sequencing datasets of mouse liver tissues exposed to PFAS to identify metabolic pathways influenced by the chemical toxicant. We integrated the transcriptome data with a mouse genome-scale metabolic model to perform in silico flux analysis and investigated reactions and genes associated with lipid and energy metabolism. Results: PFESA-BP2 exposure caused dose- and sex-dependent changes, including upregulation of fatty acid metabolism, β-oxidation, and cholesterol biosynthesis. On the contrary, triglycerides, sphingolipids, and glycerophospholipids metabolism were suppressed. Simulations from the integrated genome-scale metabolic models confirmed increased flux for mevalonate and lanosterol metabolism, supporting potential cholesterol accumulation. GenX and PFOA triggered strong PPARα-dependent responses, especially in β-oxidation and lipolysis, which were attenuated in PPARα^−/− mice. Mitochondrial fatty acid transport and acylcarnitine turnover were also disrupted, suggesting impaired mitochondrial dysfunction. Additional PFAS effects included perturbations in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and blood–brain barrier (BBB) function, pointing to broader systemic toxicity. Conclusions: Our findings highlight key metabolic signatures and suggest PFAS-mediated disruption of hepatic and possibly neurological functions. This study underscores the utility of genome-scale metabolic modeling as a powerful tool to interpret transcriptomic data and predict systemic metabolic outcomes of toxicant exposure. Full article