RESUMO
Although there is an association between income status and concentration of perfluoroalkyl and polyfluoroalkyl substance (PFAS), the association remains uncertain in patients with hypertension, hyperlipidemia, and comorbidities. Data from the 2013-2016 National Health and Nutrition Examination Survey were analyzed. A total of 2665 adults were included, and the data included participants' serum PFAS (perfluorooctanoic acid [PFOA], perfluorononaic acid, perfluorodecanoic acid, perfluoroundecanoic acid, perfluorohexane sulfonic acid, and perfluorooctane sulfonic acid) levels and selected covariates. Multivariate linear regression models were used to examine the association between the ratio of family income to poverty (PIR) and individual serum PFAS concentrations in the hypertensive and/or hyperlipidemia groups after adjusting for covariates. The potential effects of sex and age on the results were explored using stratified analysis. A mediating effect model was used to explore the mediating effects of body mass index (BMI) and waist circumference on the association results. After adjusting for potential confounders, for hyperlipidemia and comorbidities (hypertension and hyperlipidemia), serum levels of multiple common PFAS increased by 0.09% (95%Confidence interval [CI] 0.02-0.15%) to 0.13% (95%CI 0.08-0.19%) and 0.10% (95%CI 0.02-0.17%) to 0.12% (95%CI 0.06-0.18%), respectively, with each 1% increase in PIR. The covariate model and stratified analyses results suggested the potential effects of different covariates such as age and sex, leading to changes in the statistical significance of the association results. BMI significantly mediated the effect of PIR on PFOA in hyperlipidemia (13%, P < 0.001). Household income in adults with hyperlipidemia and comorbidities positively correlated with serum PFAS concentration in the United States. Obesity played an indispensable mediating role in the association between economic income and PFAS concentration.
Assuntos
Fluorocarbonos , Hiperlipidemias , Hipertensão , Humanos , Feminino , Masculino , Fluorocarbonos/sangue , Hipertensão/sangue , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Adulto , Hiperlipidemias/sangue , Hiperlipidemias/epidemiologia , Estados Unidos/epidemiologia , Inquéritos Nutricionais , Idoso , Ácidos Alcanossulfônicos/sangue , Índice de Massa Corporal , Caprilatos/sangueRESUMO
BACKGROUND: Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced impacts on enterohepatic circulation may play a critical role in cardiovascular risk. OBJECTIVES: Using a mouse model with high levels of low-density and very low-density lipoprotein (LDL and VLDL, respectively) cholesterol and aortic lesion development similar to humans, the present study investigated mechanisms linking exposure to a PFAS mixture with increased cholesterol. METHODS: Male and female Ldlr-/- mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFHxS, PFNA, GenX), each at a concentration of 2mg/L, for 7 wk. Blood was collected longitudinally for cholesterol measurements, and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA sequencing. RESULTS: After 7 wk of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1.5µg/mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1.7µg/mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. Total circulating cholesterol levels were higher in PFAS-exposed mice after 7 wk (352mg/dL vs. 415mg/dL in female mice and 392mg/dL vs. 488mg/dL in male mice exposed to vehicle or PFAS, respectively). Total circulating bile acid levels were higher in PFAS-exposed mice (2,978 pg/µL vs. 8,496 pg/µL in female mice and 1,960 pg/µL vs. 4,452 pg/µL in male mice exposed to vehicle or PFAS, respectively). In addition, total fecal bile acid levels were lower in PFAS-exposed mice (1,797 ng/mg vs. 682 ng/mg in females and 1,622 ng/mg vs. 670 ng/mg in males exposed to vehicle or PFAS, respectively). In the ileum, expression levels of the apical sodium-dependent bile acid transporter (ASBT) were higher in PFAS-exposed mice. DISCUSSION: Mice exposed to a PFAS mixture displayed higher circulating cholesterol and bile acids perhaps due to impacts on enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk following PFAS exposure. https://doi.org/10.1289/EHP14339.
Assuntos
Ácidos e Sais Biliares , Fluorocarbonos , Animais , Ácidos e Sais Biliares/metabolismo , Camundongos , Fluorocarbonos/toxicidade , Masculino , Feminino , Receptores de LDL/genética , Receptores de LDL/metabolismo , Poluentes Ambientais/toxicidade , Lipídeos/sangue , Colesterol/sangue , Colesterol/metabolismo , Ácidos Alcanossulfônicos/toxicidadeRESUMO
Perfluorinated and polyfluoroalkyl substances (PFASs) are compounds characterized by at least one perfluorinated carbon atom in an alkyl chain linked to side-chain groups. Owing to their unique chemical properties, these compounds are widely used in industrial production and daily life. However, owing to anthropogenic activities, sewage discharge, surface runoff, and atmospheric deposition, PFASs have gradually infiltrated the environment and aquatic resources. With their gradual accumulation in environmental waters, PFASs have been detected in fishes and several fish-feeding species, suggesting that they are bioconcentrated and even amplified in aquatic organisms. PFASs exhibit high intestinal absorption efficiencies, and they bioaccumulate at higher trophic levels in the food chain. They can be bioconcentrated in the human body via food (e. g., fish) and thus threaten human health. Therefore, establishing an efficient analytical technique for use in analyzing PFASs in typical fish samples and providing technical support for the safety regulation and risk assessment of fish products is necessary. In this study, by combining solvent extraction and magnetic dispersion-solid phase extraction (d-SPE), an improved QuEChERS method with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the determination of 13 PFASs in fish samples. Fe3O4-TiO2 can be used as an ideal adsorbent in the removal of sample matrix interference and a separation medium for the rapid encapsulation of other solids to be isolated from the solution. Based on the matrix characteristics of the fish products and structural properties of the target PFASs, Fe3O4-TiO2 and N-propyl ethylenediamine (PSA) were employed as adsorbents in dispersive purification. The internal standard method was used in the quantitative analyses of the PFASs. To optimize the sample pretreatment conditions of analyzing PFASs, the selection of the extraction solvent and amounts of Fe3O4-TiO2 and PSA were optimized. Several PFASs contain acidic groups that are non-dissociated in acidic environments, thus favoring their entry into the organic phase. In addition, acidified acetonitrile can denature and precipitate the proteins within the sample matrix, facilitating their removal. Finally, 2% formic acid acetonitrile was used as the extraction solvent, and 20 mg Fe3O4-TiO2, 20 mg PSA and 120 mg anhydrous MgSO4 were used as purification adsorbents. Under the optimized conditions, the developed method exhibited an excellent linearity (R≥0.9973) in the range of 0.01-50 µg/L, and the limits of detection (LODs) and quantification (LOQs) ranged from 0.001-0.023 and 0.003-0.078 µg/L, respectively. The recoveries of the 13 PFASs at low, medium, and high spiked levels (0.5, 10, and 100 µg/kg) were 78.1%-118%, with the intra- and inter-day precisions of 0.2%-11.1% and 0.8%-8.7%, respectively. This method was applied in analyzing real samples, and PFASs including perfluorooctanesulfonic acid, perfluorooctanoic acid, perfluoroundecanoic acid, perfluorododecanoic acid, and perfluorotridecanoic acid, were detected in all 11 samples evaluated. This method is simple, sensitive, and suitable for use in analyzing PFASs in fish samples.
Assuntos
Peixes , Fluorocarbonos , Contaminação de Alimentos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Fluorocarbonos/análise , Animais , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos/análise , Caprilatos/análise , Ácidos Alcanossulfônicos/análiseRESUMO
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.
Assuntos
Ácidos Alcanossulfônicos , Monitoramento Ambiental , Fluorocarbonos , Poluentes Químicos da Água , Animais , New South Wales , OrnitorrincoRESUMO
Linear alkylbenzene sulfonate (LAS) is one of the most widely used anionic surfactants and a common toxic pollutant in wastewater. This study employed high throughput sequencing to explore the microbial community structure within activated sludge exposed to a high concentration of LAS. Genera such as Pseudomonas, Aeromonas, Thauera and Klebsiella exhibited a significant positive correlation with LAS concentrations. Furthermore, Comamonas and Klebsiella were significantly enriched under the stress of LAS. Moreover, bacterial strains with LAS-degrading capability were isolated and characterized to elucidate the degradation pathways. The Klebsiella pneumoniae isolate L1 could effectively transform more than 60 % of 25 mg/L of LAS within 72 h. Chemical analyses revealed that L1 utilized the LAS sulfonyl group as a sulfur source to support its growth. Genomic and transcriptomic analyses suggested that strain L1 may uptake LAS through the sulfate ABC transport system and remove sulfonate with sulfate and sulfite reductases.
Assuntos
Ácidos Alcanossulfônicos , Biodegradação Ambiental , Esgotos , Tensoativos , Tensoativos/metabolismo , Tensoativos/toxicidade , Ácidos Alcanossulfônicos/metabolismo , Ácidos Alcanossulfônicos/toxicidade , Esgotos/microbiologia , Bactérias/metabolismo , Bactérias/genética , Bactérias/efeitos dos fármacos , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Microbiota/efeitos dos fármacosRESUMO
Crop contamination of perfluoroalkyl substances (PFASs) may threaten human health, with root and leaves representing the primary uptake pathways of PFASs in crops. Therefore, it is imperative to elucidate the uptake characteristics of PFASs by crop roots and leaves as well as the critical influencing factors. In this study, the uptake and translocation of PFASs by roots and leaves of pak choi and radish were systematically explored based on perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS). Additionally, the roles of root Casparian strips, leaf stomata, and PFAS structures in the aforementioned processes were elucidated. Compared with pak choi, PFASs are more easily transferred to leaves after root uptake in radish, resulting from the lack of root Casparian strips. In pak choi root, the bioaccumulation of C4-C8 perfluoroalkyl carboxylic acids (PFCAs) showed a U-shaped trend with the increase of their carbon chain lengths, and the translocation potentials of individual PFASs from root to leaves negatively correlated with their chain lengths. The leaf uptake of PFOA in pak choi and radish mainly depended on cuticle sorption, with the evidence of a slight decrease in the concentrations of PFOA in exposed leaves after stomatal closure induced by abscisic acid. The leaf bioaccumulation of C4-C8 PFCAs in pak choi exhibited an inverted U-shaped trend as their carbon chain lengths increased. PFASs in exposed leaves can be translocated to the root and then re-transferred to unexposed leaves in vegetables. The longer-chain PFASs showed higher translocation potentials from exposed leaves to root. PFOS demonstrated a higher bioaccumulation than PFOA in crop roots and leaves, mainly due to the greater hydrophobicity of PFOS. Planting root vegetables lacking Casparian strips is inadvisable in PFAS-contaminated environments, in view of their higher PFAS bioaccumulation and considerable human intake.
Assuntos
Fluorocarbonos , Folhas de Planta , Raízes de Plantas , Fluorocarbonos/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Poluentes do Solo/metabolismo , Caprilatos/metabolismo , Ácidos Alcanossulfônicos/metabolismo , Verduras/metabolismo , Raphanus/metabolismo , Caproatos/metabolismo , Monitoramento AmbientalRESUMO
Previous studies reported that exposures to per- and polyfluoroalkyl substances (PFAS), largely in higher exposed populations, were associated with elevated risk of polycystic ovary syndrome (PCOS). However, studies evaluating PCOS risk in populations with lower background exposures to PFAS are limited. This study aimed to examine the associations between serum PFAS concentrations and PCOS risk among women attending a U.S. academic fertility clinic during 2005-2019. A total of 502 females who sought fertility evaluation and assisted reproduction treatments were included. Nine PFAS were quantified in non-fasting serum samples collected at study entry. Diagnosis of PCOS was based on the Rotterdam criteria. We used logistic regression to examine the odds ratio (OR) of PCOS in relation to individual PFAS concentrations (continuous and by tertiles) and quantile g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) to examine the joint associations of PFAS mixture with PCOS. Most participants were White and had a graduate degree or higher. Per doubling of serum perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) concentrations were associated with higher odds of PCOS [OR (95%CI): 1.70 (1.06, 2.81) and 1.45 (1.02, 2.08) for PFOS and PFHxS respectively]. There was a dose-response relationship of PFOS with PCOS risk (p of trend by PFOS tertiles = 0.07). Both QGC and BKMR identified PFOS as the most important contributor among the mixture to PCOS risk. No clear joint effects were found for other PFAS or PFAS mixtures on PCOS risk. Our findings are consistent with existing evidence in populations with higher background PFAS concentrations and highlight the adverse effects of PFAS exposure on reproductive health. Findings can inform public health measures and clinical care to protect populations vulnerable to PCOS, in part, due to environmental exposures.
Assuntos
Ácidos Alcanossulfônicos , Exposição Ambiental , Poluentes Ambientais , Fluorocarbonos , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/epidemiologia , Humanos , Feminino , Fluorocarbonos/sangue , Adulto , Ácidos Alcanossulfônicos/sangue , Poluentes Ambientais/sangue , Exposição Ambiental/estatística & dados numéricos , Clínicas de Fertilização/estatística & dados numéricos , Adulto Jovem , Ácidos Sulfônicos/sangueRESUMO
The behavior and fate of PFOS (perfluorooctanesulfonate) in the aquatic environment have received great attention due to its high toxicity and persistence. The nanoscale supramolecular mechanisms of interaction between PFOS and ubiquitous EPS (exopolymers) remain unclear though EPS have been widely-known to influence the bioavailability of PFOS. Typically, the exposure patterns of PFOS in aquatic animals changed with the EPS-PFOS interaction are not fully understood. This study hypothesized that PFOS exposure and accumulation pathways depended on the PFOS-EPS interactive assembly behavior and animal species. Two model animals, zebrafish and chironomid larvae, with different feeding habitats were chosen for the exposure and accumulation tests at the environmental concentrations of PFOS in the absence and presence of EPS. It was found that PFOS triggered the self-assembly of EPS to form large aggregates which significantly trapped PFOS. PFOS accumulation was significantly promoted in zebrafish but drastically reduced in chironomid larvae because of the nanoscale interactive assembly between EPS and PFOS. The decreased dermal uptake but increased oral uptake of PFOS by zebrafish with large mouthpart size could be ascribed to the increased ingestion of PFOS-enriched EPS aggregates as food. For the chironomid larvae with small mouthpart size, the PFOS-EPS assemblies reduced the dermal, oral and intestinal uptake of PFOS. The nano-visualization evidences confirmed that the PFOS-enriched EPS-PFOS assemblies blocked PFOS penetration through skin of both animals. These findings provide novel knowledge about the ecological risk of PFOS in aquatic environments.
Assuntos
Ácidos Alcanossulfônicos , Chironomidae , Fluorocarbonos , Larva , Poluentes Químicos da Água , Peixe-Zebra , Animais , Ácidos Alcanossulfônicos/metabolismo , Ácidos Alcanossulfônicos/toxicidade , Fluorocarbonos/metabolismo , Fluorocarbonos/toxicidade , Chironomidae/metabolismo , Chironomidae/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo , Larva/metabolismo , Larva/efeitos dos fármacos , EcossistemaRESUMO
Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS. We identified 192 and 82 key genes related to hepatocytes exposed to PFOA and PFOS, respectively. The functional enrichment analysis of key genes suggested cellular senescence may be important in PFOA/PFOS-induced hepatotoxicity. The in vitro models revealed that PFOA/PFOS led to hepatocyte senescence by increasing the activity of SA-ß-gal, inducing mitochondrial dysfunction, impacting cell cycle arrest, and elevating the expressions of p21, p53, IL-1ß, and SASP-related cytokines. The drug-target gene set enrichment analysis method was employed to compare the transcriptome data from the Gene Expression Omnibus database (GEO), Comparative Toxicogenomics Database (CTD), and the high-throughput experiment- and reference-guided database (HERB), and 21 traditional Chinese medicines (TCMs) were identified that may alleviate PFOA/PFOS-induced liver aging. The experimental results of co-exposure to PFOA/PFOS and TCMs showed that sanguinarine has particular promise in alleviating cellular senescence caused by PFOA/PFOS. Further investigations revealed that the mTOR-p53 signaling pathway was involved in PFOA/PFOS-mediated hepatic senescence and can be blocked using sanguinarine.
Assuntos
Ácidos Alcanossulfônicos , Caprilatos , Senescência Celular , Fluorocarbonos , Hepatócitos , Isoquinolinas , Fluorocarbonos/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Senescência Celular/efeitos dos fármacos , Caprilatos/toxicidade , Humanos , Ácidos Alcanossulfônicos/toxicidade , Isoquinolinas/farmacologia , Benzofenantridinas/farmacologia , Biologia Computacional , Animais , Células Hep G2 , Transdução de Sinais/efeitos dos fármacosRESUMO
Per- and polyfluoroalkyl substances (PFASs) are prevalently present in oceans, posing potential health risks to organisms and humans. However, information of PFAS distribution in remote open oceans is limited. In the Kuroshio Extension region of Northwest Pacific Ocean (6 stations), samples of 84 seawater (0-5800 m), 9 sediments, and 9 organisms were taken, and 25, 10, and 15 out of 29 PFASs were identified, respectively, with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonates (PFOS) as the most dominant PFASs. In seawater, ΣPFASs concentration decreased from the Kuroshio region (4.47 ng/L) to the Oyashio region (3.15 ng/L), and decreased with increasing seawater depth under the function of biological and physical pumps. Additionally, 12 precursors and emerging PFASs, including perfluorooctane sulfonamide (FOSA, 0.20 ng/L), were detected. In sediment, PFASs (5.92-12.97 pg/g) were identified at depths exceeding 5000 m, including 3 precursors (e.g., FOSA, 0.82 pg/g). ΣPFASs contents were 27.12, 31.47 and 36.97 ng/g (dry weight) in brown algae (Phaeophyceae), barnacles (Balanus), and lanternfish (Myctophiformes), respectively, in which two precursors (e.g., FOSA, 0.09-0.12 ng/g) were also identified. A correlation with the trophic position was found for PFOA bioaccumulation. These findings provide useful information on PFAS distribution in the global open ocean environments.
Assuntos
Ácidos Alcanossulfônicos , Monitoramento Ambiental , Fluorocarbonos , Água do Mar , Poluentes Químicos da Água , Oceano Pacífico , Poluentes Químicos da Água/análise , Animais , Água do Mar/química , Bioacumulação , Sedimentos Geológicos/química , CaprilatosRESUMO
Endocrine disruptors (EDs) pose significant risks to human and environmental health, with potential implications for neurotoxicity. This study investigates the synergistic neurotoxic effects of perfluorooctane sulfonate (PFOS) and glyphosate (GLY), two ubiquitous EDs, using SHSY5Y neuronal and C6 astrocytic cell lines. While individual exposures to PFOS and glyphosate at non-toxic concentrations did not induce significant changes, their combination resulted in a marked increase in oxidative stress and neuroinflammatory responses. Specifically, the co-exposure led to elevated levels of interleukin-6, tumor necrosis factor alpha, and interferon gamma, along with reduced interleukin-10 expression, indicative of heightened neuroinflammatory processes. These findings underscore the importance of considering the synergistic interactions of EDs in assessing neurotoxic risks and highlight the urgent need for further research to mitigate the adverse effects of these compounds on neurological health.
Assuntos
Ácidos Alcanossulfônicos , Disruptores Endócrinos , Fluorocarbonos , Glicina , Glifosato , Glicina/análogos & derivados , Glicina/toxicidade , Fluorocarbonos/toxicidade , Disruptores Endócrinos/toxicidade , Humanos , Ácidos Alcanossulfônicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular Tumoral , Linhagem Celular , Animais , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Herbicidas/toxicidade , Citocinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , RatosRESUMO
Per- and polyfluoroalkyl substances (PFAS) are anthropogenic organofluorine compounds that persist indefinitely in the environment and bioaccumulate throughout all trophic levels. Biomonitoring efforts have detected multiple PFAS in the serum of most people. Immune suppression has been among the most consistent effects of exposure to PFAS. PFAS often co-occur as mixtures in the environment, however, few studies have examined immunosuppression of PFAS mixtures or determined whether PFAS exposure affects immune function in the context of infection. In this study, mixtures containing two or four different PFAS and a mouse model of infection with influenza A virus (IAV) were used to assess immunotoxicity of PFAS mixtures. PFAS were administered via the drinking water as either a binary mixture of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) or quaternary mixture of PFOS, PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). The results indicated that the binary mixture affected the T-cell response, while the quaternary mixture affected the B-cell response to infection. These findings indicate that the immunomodulatory effects of PFAS mixtures are not simply additive, and that the sensitivity of immune responses to PFAS varies by cell type and mixture. The study also demonstrates the importance of studying adverse health effects of PFAS mixtures.
Assuntos
Ácidos Alcanossulfônicos , Caprilatos , Fluorocarbonos , Vírus da Influenza A , Infecções por Orthomyxoviridae , Fluorocarbonos/efeitos adversos , Fluorocarbonos/toxicidade , Animais , Camundongos , Vírus da Influenza A/imunologia , Ácidos Alcanossulfônicos/toxicidade , Ácidos Alcanossulfônicos/efeitos adversos , Infecções por Orthomyxoviridae/imunologia , Caprilatos/toxicidade , Caprilatos/efeitos adversos , Humanos , Feminino , Camundongos Endogâmicos C57BL , Influenza Humana/imunologia , Modelos Animais de Doenças , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacosRESUMO
BACKGROUND: Per- and polyfluoroalkyl Substances (PFAS) are synthetic chemicals widely detected in humans and the environment. Exposure to perfluorooctanesulfonic acid (PFOS) or perfluorohexanesulfonic acid (PFHxS) was previously shown to cause dark-phase hyperactivity in larval zebrafish. OBJECTIVES: The objective of this study was to elucidate the mechanism by which PFOS or PFHxS exposure caused hyperactivity in larval zebrafish. METHODS: Swimming behavior was assessed in 5-d postfertilization (dpf) larvae following developmental (1-4 dpf) or acute (5 dpf) exposure to 0.43-7.86µM PFOS, 7.87-120µM PFHxS, or 0.4% dimethyl sulfoxide (DMSO). After developmental exposure and chemical washout at 4 dpf, behavior was also assessed at 5-8 dpf. RNA sequencing was used to identify differences in global gene expression to perform transcriptomic benchmark concentration-response (BMCT) modeling, and predict upstream regulators in PFOS- or PFHxS-exposed larvae. CRISPR/Cas9-based gene editing was used to knockdown peroxisome proliferator-activated receptors (ppars) pparaa/ab, pparda/db, or pparg at day 0. Knockdown crispants were exposed to 7.86µM PFOS or 0.4% DMSO from 1-4 dpf and behavior was assessed at 5 dpf. Coexposure with the ppard antagonist GSK3787 and PFOS was also performed. RESULTS: Transient dark-phase hyperactivity occurred following developmental or acute exposure to PFOS or PFHxS, relative to the DMSO control. In contrast, visual startle response (VSR) hyperactivity only occurred following developmental exposure and was irreversible up to 8 dpf. Similar global transcriptomic profiles, BMCT estimates, and enriched functions were observed in PFOS- and PFHxS-exposed larvae, and ppars were identified as putative upstream regulators. Knockdown of pparda/db, but not pparaa/ab or pparg, blunted PFOS-dependent VSR hyperactivity to control levels. This finding was confirmed via antagonism of ppard in PFOS-exposed larvae. DISCUSSION: This work identifies a novel adverse outcome pathway for VSR hyperactivity in larval zebrafish. We demonstrate that developmental, but not acute, exposure to PFOS triggered persistent VSR hyperactivity that required ppard function. https://doi.org/10.1289/EHP13667.
Assuntos
Fluorocarbonos , Larva , Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Fluorocarbonos/toxicidade , Larva/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Receptores Ativados por Proliferador de Peroxissomo/genética , Ácidos Alcanossulfônicos/toxicidade , Reflexo de Sobressalto/efeitos dos fármacos , Ácidos Sulfônicos/toxicidade , NataçãoRESUMO
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are global contaminants. Seafood consumption is a possible PFAS exposure route to humans while the isomer specific analysis has not been conducted. METHODS: Perfluorooctane sulfonate (PFOS), perfluoroheptane sulfonate (PFHpS) and perfluorohexane sulfonate (PFHxS) were investigated in residents of Kyoto, Japan (n = 51). The relationship between plasma PFAS and seafood consumption biomarker, the ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) was examined by multiple regression analysis. RESULTS: Linear PFOS concentrations showed a significant positive correlation with the EPA/AA ratio in plasma samples (ß = 6.80, p = 0.0014). Linear PFHpS was marginally associated with EPA/AA ratio (ß = 0.178, p = 0.0874). Branched PFOS isomers and PFHxS had no associations with EPA/AA ratios. CONCLUSION: Seafood intake may be a significant exposure pathway for PFAS, such as PFOS but the isomers differ.
Assuntos
Ácidos Alcanossulfônicos , Biomarcadores , Ácido Eicosapentaenoico , Fluorocarbonos , Alimentos Marinhos , Fluorocarbonos/sangue , Ácidos Alcanossulfônicos/sangue , Humanos , Ácido Eicosapentaenoico/sangue , Alimentos Marinhos/análise , Biomarcadores/sangue , Japão , Masculino , Feminino , Pessoa de Meia-Idade , Isomerismo , Idoso , Adulto , Poluentes Ambientais/sangue , Contaminação de Alimentos/análiseRESUMO
Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic surfactants of over 12,000 compounds that are incorporated into numerous products for their chemical and physical properties. Studies have associated PFAS with adverse health effects. Although there is a high potential for dermal exposure, these studies are lacking. The present study evaluated the systemic and immunotoxicity of subchronic 28- or 10-days of dermal exposure, respectively, to PFHpS (0.3125-2.5% or 7.82-62.5 mg/kg/dose) or PFOS (0.5% or 12.5 mg/kg/dose) in a murine model. Elevated levels of PFHpS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. PFHpS induced significantly increased relative liver weight, significantly decreased relative spleen and thymus weight, altered serum chemistries, and altered histopathology. Additionally, PFHpS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen of genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells and CD11b+ monocyte and/or macrophages in the spleen along with decreases in eosinophils and dendritic cells in the skin. These findings support PFHpS absorption through the skin leading to liver damage and immune suppression.
Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Animais , Fluorocarbonos/toxicidade , Fluorocarbonos/administração & dosagem , Camundongos , Ácidos Alcanossulfônicos/toxicidade , Ácidos Alcanossulfônicos/administração & dosagem , Feminino , Humanos , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Ácidos Sulfônicos/toxicidade , Ácidos Sulfônicos/administração & dosagem , Administração Tópica , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , Pele/efeitos dos fármacos , Pele/imunologia , Pele/patologiaRESUMO
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous contaminants which are also found in drinking water. Concentration levels in drinking water vary widely and range from a very low contribution to total daily exposure for humans to being the major source of uptake of PFAS. PFAS concentrations in Norwegian drinking water has been rarely reported. We investigated concentrations of 31 PFAS in 164 water samples, representing both source water (i.e., before drinking water treatment) and finished drinking water. Samples were taken from 18 different water bodies across Norway. The 17 waterworks involved supply drinking water to 41 % of the Norwegian population. Only four of the waterworks utilised treatment involving activated carbon which was able to significantly reduce PFAS from the source water. Samples of source water from waterworks not employing activated carbon in treatment were therefore considered to represent drinking water with regards to PFAS (142 samples). All samples from one of the water bodies exceeded the environmental quality standard (EQS) for perfluorooctane sulfonic acid (PFOS) according to the water framework directive (0.65 ng/L). No concentrations exceeded the sum of (20) PFAS (100 ng/L) specified in the EU directive 2020/2184 for drinking water. Several EU countries have issued lower guidelines for the sum of the four PFAS that the European Food Safety Authority (EFSA) has established as the tolerable weekly intake (TWI) for PFOS, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Denmark and Sweden have guidelines specifying 2 and 4 ng/L for the sum of these PFAS. Only one of the 142 drinking water samples exceeded the Danish TWI and contained a sum of 6.6 ng/L PFAS. A population exposure model, for individuals drinking water from the investigated sources, showed that only 0.5 % of the population was receiving PFAS concentrations above the Danish limit of 2 ng/L.
Assuntos
Água Potável , Monitoramento Ambiental , Fluorocarbonos , Poluentes Químicos da Água , Noruega , Água Potável/química , Fluorocarbonos/análise , Poluentes Químicos da Água/análise , Ácidos Alcanossulfônicos/análise , HumanosRESUMO
Per- and polyfluoroalkyl substances (PFAS) are a class of thousands of man-made chemicals that are persistent and highly stable in the environment. Fish consumption has been identified as a key route of PFAS exposure for humans. However, routine fish monitoring targets only a handful of PFAS, and non-targeted analyses have largely only evaluated fish from heavily PFAS-impacted waters. Here, we evaluated PFAS in fish fillets from recreational and drinking water sources in central North Carolina to assess whether PFAS are present in these fillets that would not be detected by conventional targeted methods. We used liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) to collect full scan feature data, performed suspect screening using an in-house library of 100 PFAS for high confidence feature identification, searched for additional PFAS features using non-targeted data analyses, and quantified perfluorooctanesulfonic acid (PFOS) in the fillet samples. A total of 36 PFAS were detected in the fish fillets, including 19 that would not be detected using common targeted methods, with a minimum of 6 and a maximum of 22 in individual fish. Median fillet PFOS levels were concerningly high at 11.6 to 42.3 ppb, and no significant correlation between PFOS levels and number of PFAS per fish was observed. Future PFAS monitoring in this region should target more of these 36 PFAS, and other regions not considered heavily PFAS contaminated should consider incorporating non-targeted analyses into ongoing fish monitoring studies.