Assessment of cardiotoxicity induced by PFOS exposure and mechanism research via untarget metabolomics.

Perfluorooctane sulfonate (PFOS), widely used in various industrial and commercial materials, can accumulate in the human body due to its high environmental stability, and thus potentially has cardiotoxicity. We assess cardiotoxicity through rat exposure to PFOS by intraperitoneal injection. Untargeted metabolomic analysis was used to explore the potential cardiotoxicity mechanism of PFOS. In vivo, PFOS exposure increases pro-inflammatory factors TNF-α and IL-1ß and decreases anti-inflammatory factors IL-10 and TGF-ß. PFOS exposure causes pathological changes in cardiac tissue and increases cardiac injury markers brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), C-reactive protein (CRP) in serum and triglyceride (TG), total cholesterol (TC) and ox-LDL in plasma. Increased expression of plasminogen activator inhibitor-1 (PAI-1) and CD36 indicates that PFOS exacerbates cardiac fibrosis. Untargeted metabolites analysis revealed 414 small molecule metabolites and 33 metabolites that differed after PFOS exposure, and identified 3 potential metabolic pathways. In conclusion, our study shows the inflammatory reactions involved in PFOS cardiotoxicity, and identifies potential pathways and differential metabolites involved in PFOS toxicity.

Concentration and health risk assessment of per- and polyfluoroalkyl substances in cosmetic and personal care products.

Per and polyfluoroalkyl substances (PFAS) are toxicologically concerning because of their potential to bioaccumulate and their persistence in the environment and the human body. We determined PFAS levels in cosmetic and personal care products and assessed their health risks. We investigated the trends in concentrations and types of PFAS contaminants in cosmetic and personal care products before and after perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were added to the list of persistent organic pollutants. The total PFAS concentration ranged from 1.98 to 706.75 ng g-1. The hazard quotients (HQs) for PFOA, PFOS and perfluorobutanesulfonic acid (PFBS) were lower than 1, indicating no appreciable risk to consumers. Assuming the simultaneous use of all product types and the worst-case scenario for calculations, perfluoroalkyl carboxylic acids and perfluoroalkane sulfonic acids (PFSAs) also had hazard indices lower than 1. We found that adverse effects are unlikely to occur when each type of cosmetic is used separately, or even when all product types are used together. Nevertheless, the persistence and bioaccumulation characteristics of additional PFAS present in cosmetics continue to be a cause for concern. Further research is necessary to investigate the long-term impacts of using such cosmetics and the associated risks to human health.

PFAS distribution in cascade derived foam at wastewater treatment plants: The role of non-linear drainage, collapse induced enrichment, and implications for removal.

Per- and polyfluorinated alkyl substances (PFAS) enrichment in foam was investigated for the first time at a wastewater treatment plant cascade. A novel sampling device was utilized to allow spatial and temporal heterogeneity in PFAS concentrations and liquid content to be characterized. Concentrations of 8 PFAS compounds were normalized to liquid content and fit to a power law model revealing strong correlation (R2 = 0.91) between drainage induced enrichment and PFAS molar volume. Short chain PFAS such as perfluorobutanoate (PFBA) exhibited minor to no enrichment factors in foam (0.24-5.9) compared to effluent concentrations across the range of foam liquid contents (0.28-6.24 %), while long chain compounds such as perfluorooctane sulfonate (PFOS) became highly enriched with factors of 295-143,000. A conceptual model is proposed to explain higher than expected enrichment of more surface-active PFAS relative to liquid content, which combines continuous partitioning of PFAS to air bubbles during foam formation with additional partitioning during non-linear drainage and foam collapse, both controlled by their affinity for the air-water interface. Scoping calculations suggest the majority of PFOS and other long chain PFAS may be removed if foam is continuously collected with potential to reduce waste volume under economic barriers for current destructive technologies.

A research synthesis of humans, animals, and environmental compartments exposed to PFAS: A systematic evidence map and bibliometric analysis of secondary literature.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a class of widely used anthropogenic chemicals. Concerns regarding their persistence and potential adverse effects have led to multiple secondary research publications. Here, we aim to assess the resulting evidence base in the systematic secondary literature by examining research gaps, evaluating the quality of reviews, and exploring interdisciplinary connections. METHODS: This study employed a systematic evidence-mapping approach to assess the secondary literature on the biological, environmental, and medical aspects of exposure to 35 fluorinated compounds. The inclusion criteria encompassed systematic reviews published in peer-reviewed journals, pre-prints, and theses. Comprehensive searches across electronic databases and grey literature identified relevant reviews. Data extraction and synthesis involved mapping literature content and narrative descriptions. We employed a modified version of the AMSTAR2 checklist to evaluate the methodological rigour of the reviews. A bibliometric data analysis uncovered patterns and trends in the academic literature. A research protocol for this study was previously pre-registered (osf.io/2tpn8) and published (Vendl et al., Environment International 158 (2022) 106973). The database is freely accessible through the interactive and user-friendly web application of this systematic evidence map at https://hi-this-is-lorenzo.shinyapps.io/PFAS_SEM_Shiny_App/. RESULTS: Our map includes a total of 175 systematic reviews. Over the years, there has been a steady increase in the annual number of publications, with a notable surge in 2021. Most reviews focused on human exposure, whereas environmental and animal-related reviews were fewer and often lacked a rigorous systematic approach to literature search and screening. Review outcomes were predominantly associated with human health, particularly with reproductive and children's developmental health. Animal reviews primarily focused on studies conducted in controlled laboratory settings, and wildlife reviews were characterised by an over-representation of birds and fish species. Recent reviews increasingly incorporated quantitative synthesis methodologies. The methodological strengths of the reviews included detailed descriptions of study selection processes and disclosure of potential conflicts of interest. However, weaknesses were observed in the critical lack of detail in reporting methods. A bibliometric analysis revealed that the most productive authors collaborate within their own country, leading to limited and clustered international collaborations. CONCLUSIONS: In this overview of the available systematic secondary literature, we map literature content, assess reviews' methodological quality, highlight data gaps, and draw research network clusters. We aim to facilitate literature reviews, guide future research initiatives, and enhance opportunities for cross-country collaboration. Furthermore, we discuss how this systematic evidence map and its publicly available database benefit scientists, regulatory agencies, and other stakeholders by providing access to current systematic secondary literature on PFAS exposure.

Effect of short-term sample storage and preparatory conditions on losses of 18 per- and polyfluoroalkyl substances (PFAS) to container materials.

There is a lack of agreement on a suitable container material for per- and polyfluoroalkyl substances (PFAS) analysis, particularly at trace levels. In this study, the losses of 18 short- and long-chain (C4-C10) PFAS to commonly used labware materials (high-density polyethylene (HDPE), polypropylene (PP), polystyrene (PS), polypropylene co-polymer (PPCO), polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), and glass were investigated. The influence of sample storage and preparation conditions, i.e., storage time, solvent composition, storage temperatures (4 °C and 20 °C), and sample agitation techniques (shaking and centrifugation) on PFAS losses to the container materials were investigated. The results showed higher losses for most of the considered PFAS (up to 50.9%) in 100% aqueous solutions after storage for 7 days regardless of the storage temperature compared to those after 3 days. Overall, the order of losses to different materials varied for individual PFAS, with the highest losses of long-chain PFAS observed to PP and HDPE after 7-day storage at room temperature. The addition of methanol to aqueous PFAS solutions reduced the losses of long-chain PFAS to all tested materials. The use of sample centrifugation and shaking did not influence the extent of losses for most of the PFAS in 80:20 water:methanol (%, v/v) to container materials except for 8:2 fluorotelomer sulfonic acid (8:2 FTS), 9-chlorohexadecafluoro-3-oxanone-1-sulfonic acid (9Cl-PF3ONS), perfluorodecanoic acid (PFDA) and 4:2 fluorotelomer sulfonic acid (4:2 FTS). This study demonstrates lower losses of both long- and short-chain PFAS to glass and PET. It also highlights the need for caution when deciding on sample preparatory steps and storage during the analysis of PFAS.

Elucidating the degradation mechanisms of perfluorooctanoic acid and perfluorooctane sulfonate in various environmental matrices: a review of green degradation pathways.

Given environmental persistence, potential for bioaccumulation, and toxicity of Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the scientific community has increasingly focused on researching their toxicology and degradation methods. This paper presents a survey of recent research advances in the toxicological effects and degradation methods of PFOA and PFOS. Their adverse effects on the liver, nervous system, male reproductive system, genetics, and development are detailed. Additionally, the degradation techniques of PFOA and PFOS, including photochemical, photocatalytic, and electrochemical methods, are analyzed and compared, highlighted the potential of these technologies for environmental remediation. The biotransformation pathways and mechanisms of PFOA and PFOS involving microorganisms, plants, and enzymes are also presented. As the primary green degradation pathway for PFOA and PFOS, Biodegradation uses specific microorganisms, plants or enzymes to remove PFOA and PFOS from the environment through redox reactions, enzyme catalysis and other pathways. Currently, there has been a paucity of research conducted on the biodegradation of PFOA and PFOS. However, this degradation technology is promising owing to its specificity, cost-effectiveness, and ease of implementation. Furthermore, novel materials/methods for PFOA and PFOS degradation are presented in this paper. These novel materials/methods effectively improve the degradation efficiency of PFOA and PFOS and provide new ideas and tools for the degradation of PFOA and PFOS. This information can assist researchers in identifying flaws and gaps in the field, which can facilitate the formulation of innovative research ideas.

Vesicles exhibit high-performance removal of per-and polyfluoroalkyl substances (PFAS) depending on their hydrophobic groups.

The removal of per- and polyfluoroalkyl substances (PFAS) from drinking water is urgently needed. Here, we demonstrated high performance of vesicles on PFAS adsorption. Vesicles used in this study were enclosed amphiphile bilayers keeping their hydrophobic groups inside and their hydrophilic groups outside in water. The distribution coefficient Kd of perfluorooctane sulfonic acid (PFOS) for vesicles was 5.3 × 105 L/kg, which is higher than that for granulated activated carbon (GAC), and Kd of perfluorooctanoic acid (PFOA) for vesicles was 103-104 L/kg. The removal efficiencies of PFOA and PFOS adsorption on DMPC vesicles were 97.1 ± 0.1% and 99.4 ± 0.2%, respectively. The adsorption behaviors of PFOA and PFOS on vesicles were investigated by changing the number of cis-double bonds in the hydrophobic chains of the vesicle constituents. Moreover, vesicles formed by membranes in the different phases were also tested. The results revealed that, when vesicles are formed of a membrane in the liquid-crystalline (liquid-like) phase, the adsorption amounts of both PFOA and PFOS increased as the cis-double bond in the hydrocarbon chains decreased, which is considered due to molecular shape similarity. When vesicles are formed of a membrane in the gel (solid-like) phase, they do not adsorb PFAS as much as in the liquid-crystalline phase, even though the hydrocarbon chains do not have any cis-double bond. Our findings demonstrate that vesicles can be utilized as PFAS adsorbents by optimizing the structure of vesicle constituents and their thermodynamical phase. Indeed, the vesicles (DMPC) were demonstrated that they can adsorb PFOA and PFOS, and be coagulated by a coagulant even in environmental water. The coagulation will enable the removal of PFOA and PFOS from the water after adsorption.

Perfluorooctane Sulfonate Exposure Induces Cardiovascular Dysfunction in Female Rats: Role of Ovaries.

Per- and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants frequently detected in drinking water worldwide. Reports linking PFAS exposure to cardiovascular disease have increased significantly in recent years. Furthermore, women appear to be more susceptible to the adverse effects of PFAS. However, the potential role of ovaries in the increased vulnerability of females to PFAS-related health effects remains unknown. In this study, we investigated the impact of perfluorooctane sulfonate (PFOS), a prominent PFAS, on the cardiovascular function in female rats with intact ovaries and ovariectomized (OVX) females. Bilateral OVX or sham surgeries were performed in 8-week-old female SD rats. Following recovery from surgeries, the rats were given drinking water containing 50 µg/mL of PFOS for 3 weeks. Control groups received PFOS-free water. PFOS exposure significantly reduced body weight but increased blood pressure similarly in both intact and OVX rats. Echocardiography analysis revealed that PFOS exposure decreased cardiac output, end-systolic volume, and end-diastolic volume in intact but not OVX rats. Vascular function studies demonstrated that PFOS equally reduced endothelium-dependent and -independent relaxation responses in intact and OVX rats. The endothelium-independent contractile responses were more pronounced in both intact and OVX rats. eNOS protein levels were similarly decreased in both intact and OVX rats. In conclusion, PFOS affects cardiac function through hormone-dependent mechanisms, while vascular function is impaired independent of ovarian status, indicating an intricate interplay between PFOS exposure, ovarian status, and cardiovascular function.

Multicomponent and Surface Charge Effects on PFOS Sorption and Transport in Goethite-Coated Porous Media under Variable Hydrochemical Conditions.

Perfluorooctanesulfonate (PFOS), a toxic anionic perfluorinated surfactant, exhibits variable electrostatic adsorption mechanisms on charge-regulated minerals depending on solution hydrochemistry. This work explores the interplay of multicomponent interactions and surface charge effects on PFOS adsorption to goethite surfaces under flow-through conditions. We conducted a series of column experiments in saturated goethite-coated porous media subjected to dynamic hydrochemical conditions triggered by step changes in the electrolyte concentration of the injected solutions. Measurements of pH and PFOS breakthrough curves at the outlet allowed tracking the propagation of multicomponent reactive fronts. We performed process-based reactive transport simulations incorporating a mechanistic network of surface complexation reactions to quantitatively interpret the geochemical processes. The experimental and modeling outcomes reveal that the coupled spatio-temporal evolution of pH and electrolyte fronts, driven by the electrostatic properties of the mineral, exerts a key control on PFOS mobility by determining its adsorption and speciation reactions on goethite surfaces. These results illuminate the important influence of multicomponent transport processes and surface charge effects on PFOS mobility, emphasizing the need for mechanistic adsorption models in reactive transport simulations of ionizable PFAS compounds to determine their environmental fate and to perform accurate risk assessment.

Super-resistance of PFOS in water: Is it beatable?

In this study, we present research on PFOS occurrence in surface and groundwater in Croatia. PFOS was detected and quantified at ultra-low concentrations (even ng/L) by means of LC-QTOF-MS analysis. PFOS was treated with solar photocatalysis using different reactor types, different irradiation intensities and photocatalytic formulations. Most experiments ended with only a slight change in PFOS concentrations, proving its super-resistance toward UV irradiation and oxidative species, e.g. OH radicals. In certain experiments, PFOS degradation extents were approximately 20% after 120 min of the photocatalytic process. Additionally, photocatalysis was coupled with ultrasound to increase PFOS degradation products, we discussed the tentative degradation mechanism and proposed a solution how to possibly beat its super-resistance.

Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.

Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions. Each hMO-MPS consists of an hMO on a fully 3D printed holder device with a perfusable organoid adhesion layer for enhancing air-liquid interface culturing. Leveraging the unique, simply-fabricated holder devices, hMO-MPSs are scalable, easy to use, and compatible with conventional well-plates, and allow easy transfer onto a multiple-electrode array (MEA) system for plug-and-play measurement of neural activity. Interestingly, the neural activity of hMO-MPSs initially increased and subsequently decreased by exposure to a concentration range of 0, 30, 100, to 300 µM of PFOS. Furthermore, PFOS exposure impaired neural development and promoted neuroinflammation in the engineered hMO-MPSs. Along with PFOS, our platform is broadly applicable for studies toxicology of various other environmental pollutants.

PFOS impairs cardiac function and energy metabolism under high-fat diet: Insights into role of circulating macrophage emphasized by exposure distribution.

Per- and polyfluoroalkyl substances (PFAS), widely utilized in consumer products, have been linked to an increased risk of cardiovascular disease (CVD). With the increasing prevalence of high-fat diet, a common risk factor for CVD, the PFAS exposed populations who consume a high-fat diet will inevitably grow and may have a higher CVD risk. However, the potential toxic effect and mode of action remain elusive. We constructed a mouse model orally exposed to perfluorooctane sulfonate (PFOS), a prototypical PFAS, and fed a high-fat diet. PFOS exposure induced cardiomyopathy and structural abnormalities in the mice heart. Moreover, a characteristic of energy metabolism remodeling from aerobic to anaerobic process was observed. Interestingly, PFOS was rarely detected in heart but showed high level in serum, suggesting an indirect route of action for PFOS-caused cardiac toxicity. We further demonstrated that PFOS-caused circulating inflammation promoted metabolic remodeling and contractile dysfunction in cardiomyocytes. Wherein, PFOS stimulated the release of IL-1ß from circulating proinflammatory macrophages mediated by NF-κB and caspase-1. This study provides valuable data on PFAS-induced cardiac risks associated with exposed populations with increasing high-fat diet consumption, highlighting the significance of indirect pathways in PFOS's impact on the heart, based on the distribution of internal exposure.

Developmental perfluorooctane sulfonic acid exposure exacerbates house dust mite induced allergic responses in adult mice.

Perfluorooctane sulfonic acid (PFOS) is a long-chain per- and polyfluoroalkyl substance (PFAS), a persistent organic pollutant, which has been used in aqueous film-forming foams. Emerging epidemiological evidence indicates a significant body burden of PFOS is observed in the lungs. Furthermore, developmental PFOS exposure dysregulates lung development and exacerbates eosinophilic inflammation, which are critical risk factors for asthma. However, it is unknown whether PFOS exerts sex-dependent effects on house dust mite (HDM) induced asthmatic progression and allergic inflammation. In this study, timed pregnant Balb/cJ dams were dosed orally via PFOS (1.0 mg/kg/d) spiked or vehicle control mealworms from gestational day (GD) 0.5 to postnatal day (PND) 21. Subsequently, HDM (30 µg/day) was administered starting at PND 77-82 for 10 days, and the mice were sacrificed 48 h after their final treatment. The serum and lung PFOS concentrations were 3.391 ± 0.189 µg/mL and 3.567 ± 0.1676 µg/g in the offspring, respectively. Male mice exposed to PFOS + HDM showed higher total cell counts in bronchoalveolar lavage fluid (BALF), macrophage counts, and eosinophil counts compared to mice exposed to HDM alone. Female mice exposed to PFOS + HDM had increased BALF eosinophil percentage, mucous production, alternatively activated (M2) macrophage polarization, and M2-associated gene expression compared to female mice exposed to HDM alone. PFOS exposure had no significant effect on HDM-induced IL-4, IL-5, or IL-13, but RANTES was further elevated in female mice. Overall, our data suggest that developmental PFOS exposure increased the risk of exacerbated eosinophilic inflammation and M2 polarization, which were more severe in female mice, suggesting sex-dependent developmental effects of PFOS on allergic airway responses.

Perfluorooctane sulfonate-induced Sertoli cell injury through c-Jun N-terminal kinase: a study by RNA-Seq.

Per- and polyfluoroalkyl substances (PFASs) are a family of "forever chemicals" including perfluorooctane sulfonate (PFOS). These toxic chemicals do not break down in the environment or in our bodies. In the human body, PFOS and perfluoroctanoic acid (PFOA) have a half-life (T1/2) of about 4-5 yr so low daily consumption of these chemicals can accumulate in the human body to a harmful level over a long period. Although the use of PFOS in consumer products was banned in the United States in 2022/2023, this forever chemical remains detectable in our tap water and food products. Every American tested has a high level of PFAS in their blood (https://cleanwater.org/pfas-forever-chemicals). In this report, we used a Sertoli cell blood-testis barrier (BTB) model with primary Sertoli cells cultured in vitro with an established functional tight junction (TJ)-permeability barrier that mimicked the BTB in vivo. Treatment of Sertoli cells with PFOS was found to perturb the TJ-barrier, which was the result of cytoskeletal disruption across the cell cytoplasm, disrupting actin and microtubule polymerization. These changes thus affected the proper localization of BTB-associated proteins at the BTB. Using RNA-Seq transcriptome profiling, bioinformatics analysis, and pertinent biochemical and cell biology techniques, it was discovered that PFOS -induced Sertoli cell toxicity through the c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase, SAPK) and its phosphorylated/active form p-JNK signaling pathway. More importantly, KB-R7943 mesylate (KB), a JNK/p-JNK activator, was capable of blocking PFOS-induced Sertoli cell injury, supporting the notion that PFOS-induced cell injury can possibly be therapeutically managed.NEW & NOTEWORTHY PFOS induces Sertoli cell injury, including disruption of the 1) blood-testis barrier function and 2) cytoskeletal organization, which, in turn, impedes male reproductive function. These changes are mediated by JNK/p-JNK signaling pathway. However, the use of KB-R7943, a JNK/p-JNK activator was capable of blocking PFOS-induced Sertoli cell injury, supporting the possibility of therapeutically managing PFOS-induced reproductive dysfunction.

Enhancing the Thermal Mineralization of Perfluorooctanesulfonate on Granular Activated Carbon Using Alkali and Alkaline-Earth Metal Additives.

Thermal treatment has emerged as a promising approach for either the end-of-life treatment or regeneration of granular activated carbon (GAC) contaminated with per- and polyfluoroalkyl substances (PFAS). However, its effectiveness has been limited by the requirement for high temperatures, the generation of products of incomplete destruction, and the necessity to scrub HF in the flue gas. This study investigates the use of common alkali and alkaline-earth metal additives to enhance the mineralization of perfluorooctanesulfonate (PFOS) adsorbed onto GAC. When treated at 800 °C without an additive, only 49% of PFOS was mineralized to HF. All additives tested demonstrated improved mineralization, and Ca(OH)2 had the best performance, achieving a mineralization efficiency of 98% in air or N2. Its ability to increase the reaction rate and shift the byproduct selectivity suggests that its role may be catalytic. Moreover, additives reduced HF in the flue gas by instead reacting with the additive to form inorganic fluorine (e.g., CaF2) in the starting waste material. A hypothesized reaction mechanism is proposed that involves the electron transfer from O2- defect sites of CaO to intermediates formed during the thermal decomposition of PFOS. These findings advocate for the use of additives in the thermal treatment of GAC for disposal or reuse, with the potential to reduce operating costs and mitigate the environmental impact associated with incinerating PFAS-laden wastes.

Developmental PFOS exposure alters lung inflammation and barrier integrity in juvenile mice.

Emerging epidemiological evidence indicates perfluorooctane sulfonic acid (PFOS) is increasingly associated with asthma and respiratory viral infections. Animal studies suggest PFOS disrupts lung development and immuno-inflammatory responses, but little is known about the potential consequences on respiratory health and disease risk. Importantly, PFOS exposure during the critical stages of lung development may contribute to disease risk later in life. Thus, we hypothesized that developmental PFOS exposure will affect lung inflammation and alveolar/airway development in a sex-dependent manner. To address this knowledge gap, timed pregnant Balb/cJ dams were orally dosed with a PFOS (1.0, or 2.0 mg/kg/d) injected mealworm or a vehicle control daily from gestational day (GD) 0.5 to postnatal day (PND) 21, and offspring were sacrificed at PND 22-23. PFOS exposed male offspring displayed increased alveolar septa thickness. Downregulated protein staining of occludin were also observed in the lungs after PFOS exposure in male mice compared to vehicle controls, indicative of barrier dysfunction. BALF macrophages were significantly elevated at 2.0 mg/kg/d PFOS in both sexes compared to vehicles, while BALF cytokines (TNF-α, IL-6, KC, MIP-1α, MIP-1ß, and MCP-1) were suppressed in PFOS exposed male offspring compared to vehicle controls. Multiplex nucleic acid hybridization assay showed male-specific downregulation of cytokine gene expression in PFOS exposed mice compared to vehicle mice. Overall, these results demonstrate PFOS exposure exhibits male-specific adverse effects on lung development and inflammation in juvenile offspring, possibly predisposing them to later-in-life respiratory disease. Further research is required to elucidate the mechanisms underlying the sex-differentiated pulmonary toxicity of PFOS.

Four Decades of Spatiotemporal Variability of Per- and Polyfluoroalkyl Substances (PFASs) in the Baltic Sea.

Temporal and spatial variability of per- and polyfluoroalkyl substances (PFASs) in herring, cod, eelpout, and guillemot covering four decades and more than 1000 km in the Baltic Sea was investigated to evaluate the effect of PFAS regulations and residence times of PFASs. Overall, PFAS concentrations responded rapidly to recent regulations but with some notable basin- and homologue-specific variability. The well-ventilated Kattegat and Bothnian Bay showed a faster log-linear decrease for most PFASs than the Baltic Proper, which lacks a significant loss mechanism. PFOS and FOSA, for example, have decreased with 0-7% y-1 in the Baltic Proper and 6-16% y-1 in other basins. PFNA and partly PFOA are exceptions and continue to show stagnant or increasing concentrations. Further, we found that Bothnian Bay herring contained the highest concentrations of >C12 perfluoroalkyl carboxylic acids (PFCAs), likely from rivers with high loads of dissolved organic carbon. In the Kattegat, low PFAS concentrations, but a high FOSA fraction, could be due to influence from the North Sea inflow below the halocline and possibly a local source of FOSA and/or isomer-specific biotransformation. This study represents the most comprehensive spatial and temporal investigation of PFASs in Baltic wildlife while providing new insights into cycling of PFASs within the Baltic Sea ecosystem.

Association of Vitamin D with Perfluorinated Alkyl Acids in Women with and without Non-Obese Polycystic Ovary Syndrome.

BACKGROUND: Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency. METHODS: Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women (n = 30) were recruited. Paired serum samples were analyzed for PFAAs (n = 13) using high-performance liquid chromatography-tandem mass spectrometry. Tandem mass spectrometry determined levels of 25(OH)D3 and the active 1,25(OH)2D3. RESULTS: Women with and without PCOS did not differ in age, weight, insulin resistance, or systemic inflammation (C-reactive protein did not differ), but the free androgen index was increased. Four PFAAs were detected in all serum samples: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Serum PFOS was higher in PCOS versus controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, p < 0.05). Linear regression modeling showed that elevated PFHxS had higher odds of a lower 25(OH)D3 (OR: 2.919, 95% CI 0.82-5.75, p = 0.04). Vitamin D did not differ between cohorts and did not correlate with any PFAAs, either alone or when the groups were combined. When vitamin D was stratified into sufficiency (>20 ng/mL) and deficiency (<20 ng/mL), no correlation with any PFAAs was seen. CONCLUSIONS: While the analyses and findings here are exploratory in light of relatively small recruitment numbers, when age, BMI, and insulin resistance are accounted for, the PFAAs do not appear to be related to 25(OH)D3 or the active 1,25(OH)2D3 in this Caucasian population, nor do they appear to be associated with vitamin D deficiency, suggesting that future studies must account for these factors in the analysis.

PFAS transport under lower water-saturation conditions characterized with instrumented-column systems.

The transport of PFOS and PFOA in well-characterized sand was investigated for relatively low water saturations. An instrumented column was used for some experiments to provide real-time in-situ monitoring of water saturation and matric potential. The results showed that water saturations and matric potentials varied minimally during the experiments. Flow rates were monitored continuously and were essentially constant. These results demonstrate that surfactant-induced flow and other nonideal hydraulic processes did not materially impact PFAS transport for the experiment conditions. Air-water interfacial adsorption was demonstrated to provide the great majority of retention for PFOS and PFOA. Retention was significantly greater at the lower water saturations (0.35-0.45) compared to the higher saturations (∼0.66) for both PFAS, due to the larger extant air-water interfacial areas. Retardation factors were 5 and 3-times greater at the lower water saturations for PFOS and PFOA, respectively. Early breakthrough was observed for the PFAS but not for the non-reactive tracers at the lower water saturations, indicating the possibility that air-water interfacial adsorption was rate-limited to some degree. Independently determined retention parameters were used to predict retardation factors for PFOS and PFOA, which were similar to the measured values in all cases. The consistency between the predicted and measured values indicates that PFAS retention was accurately represented. In addition, air-water interfacial adsorption coefficients measured from the transport experiments were consistent with independently measured equilibrium-based values. Based on these results, it appears that the air-water interfacial adsorption processes mediating the magnitude of PFOS and PFOA retention under lower water-saturation conditions are consistent with those for higher water saturations. This provides some confidence that our understanding of PFAS retention obtained from work conducted at higher water saturations is applicable to lower water saturations.

In silico prediction of the interaction of legacy and novel per- and poly-fluoroalkyl substances (PFAS) with selected human transporters and of their possible accumulation in the human body.

Per- and poly-fluorinated compounds constitute a wide group of fluorocarbon chemicals with widespread industrial applications, ranging from non-stick coating in cookware to water surfactants, from fire-fighting foams to water-repellent coatings on textiles. Presently, over 12,000 PFAS are known worldwide. In recent years, extensive research has focused on investigating the biological effects of these molecules on various organisms, including humans. Here, we conducted in silico simulations to examine the potential binding of a representative selection of PFAS to various human proteins known to be involved in chemical transportation and accumulation processes. Specifically, we targeted human serum albumin (HSA), transthyretin (TTR), thyroxine binding protein (TBG), fatty acid binding proteins (FABPs), organic anion transporters (OATs), aiming to assess the potential for bioaccumulation. Molecular docking simulations were employed for this purpose, supplemented by molecular dynamics (MD) simulations to account for protein flexibility, when necessary. Our findings indicate that so-called "legacy PFAS" such as PFOA or PFOS exhibit a higher propensity for interaction with the analysed human protein targets compared to newly formulated PFAS, characterised by higher branching and hydrophilicity, and possibly a higher accumulation in the human body.