Flaxseed Oil Alleviates PFOS-Induced Liver Injury by Regulating Hepatic Cholesterol Metabolism.

Perfluorooctanesulfonate (PFOS) is a widespread, persistent environmental pollutant that exerts apparent liver toxicity. Flaxseed oil (FO), a dietary oil rich in α-linolenic acid, has been demonstrated to possess a diverse array of health benefits. However, whether FO protects against PFOS-induced liver injury and its underlying mechanisms remain unclear. C57/BL6 mice were orally treated with different concentrations of FO alone or in combination with 10 mg/kg of PFOS for 28 consecutive days. Blood and liver tissues were collected for proteomic, histopathological, biochemical, immunohistochemical, and molecular examinations. Results demonstrated that FO supplementation reduced PFOS-induced liver injury, as evidenced by a decrease in histopathological changes, serum transaminase (ALT and AST) levels, levels of oxidative stress, and inflammatory cytokine (TNF-α, IL-1ß, and IL-6) levels. Proteomic analyses showed that differentially expressed proteins were enriched in cholesterol metabolic pathways when comparing the PFOS group to the FO supplementation groups. The expression of cholesterol metabolism-related proteins was also subsequently measured, revealing that FO supplementation decreased the protein expressions of SREBP2, HMGCR, and LDLR while increasing the expression of CYP7A1. This study demonstrates that FO can alleviate PFOS-induced hepatotoxicity by regulating hepatic cholesterol metabolism, indicating that FO may serve as an effective dietary intervention for preventing liver injury caused by PFOS.

Sorption of PFOS onto polystyrene microplastics potentiates synergistic toxic effects during zebrafish embryogenesis and neurodevelopment.

Microplastics (MPs) have become an emerging anthropogenic pollutant, and their ability to sorb contaminants potentially enhances the threats to the ecosystem. Only a few studies are available to understand the combined effects of microplastics and other pollutants. The present study investigated the sorption of perfluorooctane sulfonic acid (PFOS) onto polystyrene microplastics (PS-MPs) at varying concentrations, using molecular dynamics simulation (MDS) to preliminarily explore the adsorption behavior. The MDS results revealed negative interaction energies between PFOS and PS-MPs, underscoring PS-MPs' role as a potential adsorbent for PFOS in an aqueous solution. Thereafter, zebrafish embryos were employed to explore the toxic effects of combined exposure to PS-MPs and PFOS. Fluorescence and Scanning Electron Microscopy (SEM) suggested PS-MP accumulation individually and in combination with PFOS on the embryonic chorion membrane. As a result, the exposed group showed increased inner pore size of the chorionic membrane and accelerated heartbeat, indicating hypoxic conditions and hindered gaseous exchange. PS-MPs aggravated the toxicity of PFOS during larval development manifested by delayed hatching rate, increased mortality, and malformation rate. Additionally, increased ROS accumulation and altered antioxidant enzymatic status were observed in all the exposed groups suggesting perturbation of the redox state. Additionally, co-exposure of zebrafish larvae to PS-MPs and PFOS resulted in an abrupt behavioral response, which decreased AChE activity and altered neurotransmitter levels. Taken together, our results emphasize that PS-MPs can act as a potential vector for PFOS, exerting synergistic toxic effects in the aquatic environment, and hence their health risks cannot be ignored.

Uptake of Per- and Polyfluoroalkyl Substances in Mixed Forages on Biosolid-Amended Farm Fields.

Models to predict perfluorooctanesulfonic acid (PFOS) concentrations in livestock based on soil concentrations are essential to guide decisions surrounding food testing and farm management. A key parameter in modeling soil-to-livestock exposure pathways is the plant transfer factor (TF) from soil into forages. Uptake of PFOS and other individual per- and polyfluoroalkyl substances (PFASs) were examined in perennial mixed grasses and legumes on PFAS-contaminated farm fields. In a field plot study, PFOS TFs were similar within each plot over three consecutive years but varied 10-fold among the four plots with mean TFs ranging from 0.026 to 0.27. In a multifarm field survey study, mean PFOS TFs ranged from 0.039 to 0.37. Increasing concentrations of two PFOS precursors in soil were significantly associated with increasing PFOS TFs. These data represent a substantial increase in empirical observations of PFAS TFs for grass-based forages for use in modeling soil-to-livestock exposure scenarios.

Stimulating Acidimicrobium sp. Strain A6 in iron-rich, acidic sediments from AFFF-impacted sites for PFAS defluorination.

Per- and polyfluoroalkyl substances (PFAS) are persistent and bioaccumulative contaminants that are widely used in industrial applications and consumer products and pose significant risks to ecosystems and human health. Acidimicrobium sp. Strain A6 (A6), which is common in acidic, and iron rich soils and sediments is capable of both anaerobic ammonium (NH4+) oxidation under iron reduction (Feammox) and defluorination of perfluorinated alkyl substances, such as perfluoroalkyl acids (PFAAs). This study investigates the potential for biostimulating A6 via the supply of NH4+ and ferric iron (Fe(III)) with the goal of defluorinating PFAAs. Sediment samples from acidic, iron-rich, AFFF (aqueous film forming foam) impacted sites were collected and incubated with added Fe(III) and NH4+. Quantitative PCR was used to track A6 numbers as well as dehalogenase and F- ion transporter genes during these incubations; changes in the microbial community structure were tracked through 16S rRNA gene sequencing. The findings reveal that the addition of Fe(III) and NH4+ stimulated the Feammox reaction and A6 growth and enhanced the degradation of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). Results also show a significant presence and activity of the above-mentioned genes in these incubations. The insights gained from this study could inform bioremediation strategies for PFAS-contaminated environments, especially in geochemical settings that favor the presence of A6.

Molecular mechanism of immunotoxicity: Binding interaction between perfluorinated compounds and human immunoglobulin G.

Perfluorinated compounds (PFCs) can induce immunotoxicity effect via binding with proteins. Immunoglobulin G (IgG) is a common four chain monomer protein in serum, and plays an important role in long-term body fluid immunity. Whether PFCs can bind with IgG and further induce immunotoxicity is not clear. Herein, fluorescence quenching assay was used to verify the PFCs-IgG binding interactions. The occurrence of fluorescence quenching phenomenon suggested that PFCs could bind to IgG. Linear fitting curves demonstrated that the binding constants (KA) for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were 2.51 × 106 L/mol and 1.58 × 105 L/mol, respectively. UV-vis spectral analysis results showed that the PFCs-IgG interactions mainly proceeded via the intercalation binding mode. Fourier transform infrared spectroscopy results revealed that PFCs preferentially bound to the C=O/N-H of IgG structure. Circular dichroism results revealed that PFCs-IgG binding induced the decrease of α-helix. Moreover, hydrogen bonds and van der Waals force dominated PFCs-IgG binding interactions. This binding process was a stable process, and its stability depended on the number of hydrogen bonds formation. This study reveals the mechanism of interaction between PFCs and IgG at the molecular level, providing a theoretical basis for the immunotoxic mechanism of PFCs.

Development, validation, and clinical assessment of a liquid chromatography-tandem mass spectrometry serum assay for per- and polyfluoroalkyl substances (PFAS) recommended by the National Academies of Science, Engineering, and Medicine (NASEM).

Per- and polyfluoroalkyl substances (PFAS) are widely used in industry, residential, and consumer products. Studies have shown associations between high PFAS exposure and adverse health effects. In 2022, the National Academies of Science, Engineering, and Medicine (NASEM) published Guidance on PFAS Exposure, Testing, and Clinical Follow-up providing laboratory and clinical direction. The Guidance suggests nine PFAS should be measured in serum or plasma specimens and summed to provide a total PFAS concentration using a NASEM-recommended method. Follow-up clinical recommendations are based on the calculated PFAS NASEM summation. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in accordance with NASEM recommendations but distinguished by the ability to separate closely related structural isomers. As part of our validation, PFAS prevalence was evaluated in a population survey comprised of clinical donor and remnant specimens (n = 1023 in total). In this study, 82.2% of the specimens had PFAS NASEM summations of 2 to < 20 ng/mL and 2.5% had a summation ≥ 20 ng/mL. The median PFAS NASEM summation was 4.65 ng/mL in this study, lower than the 7.74 ng/mL median observed in the 2017-2020 Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey (n = 3072). This lower median PFAS NASEM summation may reflect a decline in PFAS population levels over time or sample population exposure differences.

Chronic environmental level exposure to perfluorooctane sulfonate overshadows graphene oxide to induce apoptosis through activation of the ROS-p53-caspase pathway in marine medaka Oryzias melastigma.

The widespread occurrence of perfluorooctane sulfonate (PFOS) and the mass production and application of graphene oxide (GO) lead to their inevitable release and interaction in the environment, which may enhance associated toxic impacts on aquatic organisms. This study elucidates the induction of apoptosis by 60-day chronic single and mixture exposures to environmentally relevant levels of PFOS (0.5 µg/L and 5 µg/L) and GO (1 mg/L) in adult marine medaka Oryzias melastigma. Results showed a significant increase (p < 0.05) in reactive oxygen species (ROS) levels, the apoptotic positive rate in livers, and activities of caspases 3, 8, and 9 in all treated groups compared to the control. PFOS individual and PFOS-GO combined exposures significantly impacted fish growth, upregulated expressions of six apoptosis-related genes including p53, apaf1, il1b, tnfa, bcl2l1, bax, as well as enriched cell cycle and p53 signaling pathways (transcriptomic analysis) related to apoptosis compared to control group. Besides higher ROS production, GO also had a higher binding affinity to proteins than PFOS, especially to caspase 8 as revealed by molecular docking. Overall, PFOS induced ROS-p53-caspase apoptosis pathway through multi-gene regulation during single or mixture exposure, while GO single exposure induced apoptosis through tissue damage and ROS-caspase pathway activation and direct docking with caspase 8 to activate the caspase cascade. Under co-exposure, the PFOS-induced apoptotic pathway overshadowed the GO-induced pathway, due to competition for limited active sites on caspases. These findings will contribute to a better understanding of the apoptosis mechanism and ecological risks of nanomaterials and per- and polyfluoroalkyl substances in marine ecosystems.

Drug development in LMICs: could the emerging Indian model usher the southeast Asian region?

Low-income and middle-income countries (LMICs) of southeast Asia are passing through a similar phase as India in their tryst with the development of novel drugs. They are beginning to break away from their dependency on the institutions of our developed world. Over the past few years, Tata Memorial Centre-India's premier cancer centre-has shown the tenacity to develop drugs within the national frontiers. By collaborating with the domestic pharmaceutical industries, it has been able to have a steady pipeline of drugs under development, with two of them receiving marketing authorization recently. Lately, Indonesia and Vietnam have also shown an inclination towards public-private partnerships for similar motives. However, due to prolonged innovative stagnation, the entire drug development machinery faces challenges stretching all the way from arranging funds to persuading regulatory bodies. In this Viewpoint, we have tried to address a few of those issues and their potential solutions, with the intention to share our own experience which might be useful to other LMICs in connecting some adamant dots.

Characterizing PFASs in aquatic ecosystems with 3D hydrodynamic and water quality models.

Understanding how per- and polyfluoroalkyl substances (PFASs) enter aquatic ecosystems is challenging due to the complex interplay of physical, chemical, and biological processes, as well as the influence of hydraulic and hydrological factors and pollution sources at the catchment scale. The spatiotemporal dynamics of PFASs across various media remain largely unknown. Here we show the fate and transport mechanisms of PFASs by integrating monitoring data from an estuarine reservoir in Singapore into a detailed 3D model. This model incorporates hydrological, hydrodynamic, and water quality processes to quantify the distributions of total PFASs, including the major components perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), across water, particulate matter, and sediments within the reservoir. Our results, validated against four years of field measurements with most relative average deviations below 40%, demonstrate that this integrated approach effectively characterizes the occurrence, sources, sinks, and trends of PFASs. The majority of PFASs are found in the dissolved phase (>95%), followed by fractions sorbed to organic particles like detritus (1.0-3.5%) and phytoplankton (1-2%). We also assess the potential risks in both the water column and sediments of the reservoir. The risk quotients for PFOS and PFOA are <0.32 and < 0.00016, respectively, indicating an acceptable risk level for PFASs in this water body. The reservoir also exhibits substantial buffering capacity, even with a tenfold increase in external loading, particularly in managing the risks associated with PFOA compared to PFOS. This study not only enhances our understanding of the mechanisms influencing the fate and transport of surfactant contaminants but also establishes a framework for future research to explore how dominant environmental factors and processes can mitigate emerging contaminants in aquatic ecosystems.

Cation-Doped Nanocarbons for Enhanced Perfluoroalkyl Substance Removal: Exotic Bottom-Up Solution Plasma Synthesis and Characterization.

Perfluorinated alkyl substances (PFAS), such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), are pervasive organic contaminants that are widespread in aquatic environments, posing significant health risks to humans and wildlife. Due to their persistent nature, urgent removal is necessary. Conventional adsorbents are inefficient at removing PFOS and PFOA, highlighting the need for alternative materials. Herein, we present a synthetic method for quaternary ammonium cation-doped carbon nanoparticles (QACNs) using a solution plasma process for the efficient removal of PFOS and PFOA. QACN is formed simultaneously through a one-step discharge of nonequilibrium plasma at the interface of benzene and pyridinium chloride. The resulting material exhibited a high surface electrical charge and enhanced hydrophilicity as well as an amorphous structure of a nonporous nature, involving nanoparticles with an undefined shape. The obtained adsorbent demonstrated high adsorption efficiency and stability, adsorbing 998.45 and 889.37 mg g-1 of PFOS and PFOA, respectively, exceeding the efficiencies of conventional carbon-based adsorbents (80.89-313.15 mg g-1). The adsorption performance was dependent on the adsorbent dosage, pH of the solution, and the coexisting ionic species. Adsorption studies, including adsorption kinetics, isotherms, and thermodynamics, revealed that PFOS and PFOA were chemisorbed to the QACN surface, forming multilayers endothermically and spontaneously. Experimental and computational analyses revealed that adsorption primarily occurs via electronic interactions between the PFAS active sites and the quaternary ammonium group in the carbon framework. The slightly lower adsorption potential of the PFOS and PFOA fluorocarbon chains on the adsorbent was elucidated. Furthermore, the dispersibility of the adsorbent in solution significantly affected the adsorption performance. These findings highlight the potential of the novel synthetic method proposed in this study, offering a pathway for the development of highly effective carbon adsorbents for environmental remediation.

SAP130 mediates crosstalk between hepatocyte ferroptosis and M1 macrophage polarization in PFOS-induced hepatotoxicity.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant widely utilized in industrial manufacturing and daily life, leading to significant environmental accumulation and various public health issues. This study aims to characterize spliceosome-associated protein 130 (SAP130) as a key mediator of crosstalk between hepatocytes and macrophages, elucidating its role in PFOS-induced liver inflammation. The data demonstrate that PFOS exposure induces ferroptosis in mouse liver and AML12 cells. During ferroptosis, SAP130 is released from injured hepatocytes into the microenvironment, binding to macrophage-inducible C-type lectin (Mincle) and activating the Mincle/Syk signaling pathway in macrophages, ultimately promoting M1 polarization and exacerbating liver injury. Treatment with the ferroptosis inhibitor Ferrostatin-1 reduces SAP130 release, inhibits Mincle/Syk signaling activation, and mitigates inflammatory response. Furthermore, siSAP130 suppresses the activation of the Mincle signaling pathway and M1 polarization in BMDM cells. Conversely, treatment with the ferroptosis agonist Erastin enhances paracrine secretion of SAP130 and exacerbates inflammation. These findings emphasize the significance of hepatocyte-macrophage crosstalk as a critical pathway for PFOS-induced liver injury in mice while highlighting SAP130 as a pivotal regulator of ferroptosis and inflammation, thereby elucidating the potential mechanism of PFOS-induced liver injury.

PFOS and PFOSA induce oxidative stress-mediated cardiac defects in zebrafish via PPARγ and AHR pathways, respectively.

Perfluorooctane sulfonate (PFOS) and its precursor, perfluorooctane sulfonamide (PFOSA), are widespread in the environment. Evidence suggests a strong link between maternal exposure to PFOS/PFOSA and congenital heart diseases in the offspring, but the underlying mechanisms remain unclear. We hypothesized that PFOS and PFOSA induce cardiac defects through the peroxisome proliferator-activated receptor gamma (PPARγ) and aryl hydrocarbon receptor (AHR) pathways, respectively. In this study, we demonstrated that exposing zebrafish embryos to either PFOSA or PFOS caused cardiac malformations and dysfunction. Both PFOS and PFOSA induced reactive oxygen species (ROS) overproduction, mitochondrial damage, and apoptosis in zebrafish larvae hearts. Blockade of PPARγ through either pharmaceutical inhibition or genetic knockdown only attenuated the changes caused by PFOS, but not those elicited by PFOSA. Conversely, inhibition of AHR alleviated the adverse effects induced by PFOSA but not by PFOS. Both PFOSA and PFOS exhibited similar binding affinities to AHR using molecular docking techniques. The varying ability of PFOS and PFOSA to induce AHR activity in zebrafish embryonic hearts can be attributed to their different capabilities for activating PPARγ. In summary, our findings indicate that PFOS and PFOSA induce excessive ROS production in zebrafish larvae via the PPARγ and AHR pathways, respectively. This oxidative stress in turn causes mitochondrial damage and apoptosis, leading to cardiac defects.

Photo-reductive decomposition of perfluorooctane sulfonate (PFOS) and its common alternatives by UV/VUV/sulfite process: Mechanism, kinetic modeling, and water matrix effects.

The present study investigated the photo-reduction of perfluorooctane sulfonate (PFOS) and its alternatives, focusing on decomposition mechanisms, active species involvement, the influence of background water constituents, and kinetic model development. The decomposition and defluorination rates followed the order of PFOS > PFHxS > 6:2 FTSA > PFBS, with shorter chains and CH2 linkers enhancing the resistance of PFOS alternatives against the attack of hydrated electrons (eaq-). Two primary pathways were identified during the photodegradation of PFAS: (i) H/F exchange at CF bonds with the lowest bond dissociation energies (BDEs) and (ii) functional group cleavage followed by short-chain PFCAs formation, with OH playing a crucial role in transforming intermediates. Adding iodide and elevated temperatures demonstrated a synergistic effect on PFBS decomposition and defluorination, with high temperatures promoting functional group cleavage as the preferred defluorination pathway. The study examined the impact of background water constituents in different aqueous environments, from surface waters to wastewater streams and ion-exchange brine concentrates. Chloride exhibited a concentration-based dual impact on the UV/VUV/sulfite process: promotive effects at low dosages (1-10 mM) by acting as a secondary eaq- mediator, and adverse effects at high dosages (20-500 mM) due to the scavenging effect of generated chlorine radicals (Cl). High ionic strength adversely affected eaq- quantum efficiency. Additionally, bicarbonate and natural organic matter (NOM) had opposing effects on PFOS photo-reduction, primarily through eaq- scavenging and pH alteration. Kinetic modeling revealed reaction rate constants of the studied PFAS with eaq- ranging from 1.8 × 106 to 1.3 × 109 M-1 s-1, corroborating the concentration profiles of active species and highlighting the reductive nature of sulfite-mediated processes.

First report of accumulation of perfluorooctane sulfonate (PFOS) in platypuses (Ornithorhynchus anatinus) in New South Wales, Australia.

The platypus (Ornithorhynchus anatinus) is a semi-aquatic monotreme that occupies a high trophic position in the freshwater ecosystems of eastern mainland Australia and Tasmania. Platypuses are continuously exposed to anthropogenic contaminants including perfluorooctane sulfonate (PFOS). This study examined PFOS concentrations in the livers of deceased platypuses (eight wild; one captive) that were opportunistically collected across NSW over a two- and a half-year period. There was a large variation in PFOS concentrations, ranging from < 1 µg/kg to 1200 µg/kg. This study presents the first report of PFOS contamination in platypuses, revealing their PFOS levels are broadly similar to those found in river otters (Lutra canadensis) and lower than those in American mink (Mustela vison), both which occupy similar ecological niches in freshwater systems. This study raises concerns about the impact of PFOS on platypus health.

Lysosomal iron accumulation and subsequent lysosomes-mitochondria iron transmission mediate PFOS-induced hepatocyte ferroptosis.

Perfluorooctane sulfonate (PFOS) is known as a persistent organic pollutant. A significant correlation between PFOS and liver ferroptosis has been unveiled, but the precise mechanism needs to be elucidated. In prior research, we found that PFOS treatment provoked mitochondrial iron overload. In this study, we observed a gradual increase in lysosomal iron in L-O2 cells after exposure to PFOS for 0.5-24 h. In PFOS-exposed L-O2 cells, suppressing autophagy relieved the lysosomal iron overload. Inhibiting transient receptor potential mucolipin 1 (TRPML1), a calcium efflux channel on the lysosomal membrane, led to a further rise in lysosomal iron levels and decreased mitochondrial iron overload during PFOS treatment. Suppressing VDAC1, a subtype of voltage-dependent anion-selective channels (VDACs) on the outer mitochondrial membrane, had no impact on PFOS-triggered mitochondrial iron overload, whereas restraining VDAC2/3 relieved this condition. Although silencing VDAC2 relieved PFOS-induced mitochondrial iron overload, it had no effect on PFOS-triggered lysosomal iron overload. Silencing VDAC3 alleviated PFOS-mediated mitochondrial iron overload and led to an additional increase in lysosomal iron. Therefore, we regarded VDAC3 as the specific VDACs subtype that mediated the lysosomes-mitochondria iron transfer. Additionally, in the presence of PFOS, an enhanced association between TRPML1 and VDAC3 was found in mice liver tissue and L-O2 cells. Our research unveils a novel regulatory mechanism of autophagy on the iron homeostasis and the effect of TRPML1-VDAC3 interaction on lysosomes-mitochondria iron transfer, giving an explanation of PFOS-induced ferroptosis and shedding some light on the role of classic calcium channels in iron transmission.

Per- and polyfluoroalkyl substances (PFAS) in homegrown crops: Accumulation and human risk assessment.

Homegrown crops can present a significant exposure source of per- and polyfluoroalkyl substances (PFAS) to humans. Field studies studying PFAS accumulation in multiple vegetable food categories and examining the potential influence of soil characteristics on vegetable bioavailability under realistic exposure conditions are very scarce. Crop PFAS accumulation depends on a complex combination of factors. The physicochemical differences among the numerous PFAS makes risk assessment very challenging. Thus, simplification of this complexity into key factors that govern crop PFAS accumulation is critical. This study analyzed 29 targeted legacy, precursor and emerging PFAS in the vertical soil profile (0-45 cm depth), rainwater and edible crop parts of 88 private gardens, at different distances from a major fluorochemical plant. Gardens closer to the plant site showed higher soil concentrations which could be linked with historical and recent industrial emissions. Most compounds showed little variation along the soil depth profile, regardless of the distance from the plant site, which could be due to gardening practices. Annual crops consistently accumulated higher sum PFAS concentrations than perennials. Highest concentrations were observed in vegetables, followed by fruits and walnuts. Single soil-crop relationships were weak, which indicated that other factors (e.g., porewater) may be better measures of bioavailability in homegrown crop accumulation. Regression models, which additionally considered soil characteristics showed limited predictive power (all R2 ≤ 35%), possibly due to low variability in crop concentrations. Human intake estimations revealed that the PFAS exposure risk via crop consumption was similar nearby and remotely from the plant site, although the contribution to the overall dietary exposure can be relatively large. The tolerable weekly intake was frequently exceeded with respect to fruit and vegetable consumption, thus potential health risks cannot be ruled out.

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.

Occurrence of perfluoroalkyl compounds in commercially available baby food produced in different European countries - levels, dietary intake, and exposure assessment.

The presence of per- and polyfluoroalkyl substances (PFASs) in commercial baby food products from various European countries was investigated in this study. A total of 96 samples were collected and analyzed to assess PFASs levels, composition profiles, and potential dietary intake among infants. The results indicated detectable levels of PFASs in the sampled baby food products, with carboxylic acid prevalence over sulfonic acids. Among the various baby food groups studied, dry cereals exhibited the highest PFASs concentrations. This finding emphasizes the need for further monitoring and investigation of PFASs contamination in this specific food category. While the concentrations detected were generally low, they indicated the widespread presence of PFASs in various types of baby food. Furthermore, a preliminary exposure assessment was conducted on the basis of the measured PFASs concentrations, providing an initial insight into the potential exposure levels among infants from three months to three years old. Calculations based on two scenario types revealed the best-case scenario likely underestimating actual exposure, while the worst-case scenario occasionally exceeded the limits set by the governmental institutions. Further research is needed to understand the sources, pathways, and potential health effects of PFASs exposure in this vulnerable population.

Monitoring of per- and polyfluoroalkyl substances (PFAS) in human blood samples collected in three regions with known PFAS releases in the environment and three control regions in South Germany.

Per- and polyfluoroalkyl substances (PFAS) are known as persistent and bioaccumulative chemicals. The present paper describes the analysis of 969 human blood samples collected in South Germany aiming to determine whether there are statistic significant differences in internal PFAS burden between three regions with known PFAS releases in the environment (study regions) and three regions without known PFAS releases in the environment (control regions). Nine environmental relevant PFAS were analyzed, including the perfluorooctanoic acid (PFOA) substitute 3H-perfluoro-3-[(3-methoxy-propoxy)propanoic acid] ammonium salt (ADONA). We found that concentrations of PFOA and perfluorooctane sulfonate (PFOS) were higher than for all other PFAS in all of the six regions, but all medians of PFOA (between 0.8 and 0.9 ng/ml for the study and control regions) and PFOS (between 1.3 and 1.5 ng/ml for the study regions and between 1.4 and 1.5 ng/ml for the control regions) were below the human biomonitoring values (HBM) I for PFOA (2 ng/ml) und for PFOS (5 ng/ml) derived by the German HBM Commission. Concentrations of ADONA were below the limit of quantification in all samples. Minor differences were observed in PFAS blood levels between study and control regions. Especially for PFOS and PFOA the medians for women are slightly lower compared to men. In summary, individuals living in regions with known environmental PFAS contaminations show no higher internal PFAS exposure to controls and in comparison to other studies in the literature.

A novel molecular pathway of lipid accumulation in human hepatocytes caused by PFOA and PFOS.

Exposed to ubiquitously perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with non-alcoholic fatty liver disease (NAFLD), yet the underlying molecular mechanism remains elusive. The extrapolation of empirical studies correlating per- and polyfluoroalkyl substance (PFAS) exposure with NAFLD occurrence to real-life exposure was hindered by the limited availability of mechanistic data at environmentally relevant concentrations. Herein, a novel pathway mediating hepatocyte lipid accumulation by PFOA and PFOS at human-relevant dose (<10 µM) was identified by integrating CRISPR-Cas9 genome screening, concentration-dependent transcriptional assay in HepG2 cell and epidemiological data mining. 1) At genetic level, nudt7 showed the highest enriched potency among 569 NAFLD-related genes, and the transcription of nudt7 was significantly downregulated by PFOA and PFOS exposure (<7 µM). 2) At molecular pathway, upon exposure to ≤10-4 µM PFOA and PFOS, the downregulation of nudt7 transcriptional expression triggered the reduction of Ace-CoA hydrolase activity. 3) At cellular level, increased lipids were measured in HepG2 cells with PFOA and PFOS (<2 µM). Overall, we identified a novel mechanism mediated by transcriptional downregulation of nudt7 gene in hepatocellular lipid increase treated with PFOA and PFOS, which could potentially explain the NAFLD occurrence associated with exposure to PFASs in humans.