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1.
Front Endocrinol (Lausanne) ; 15: 1261008, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425754

RESUMO

Background: Previous studies showed that per- and polyfluoroalkyl substances (PFAS), which are widely found in the environment, can disrupt endocrine homeostasis when they enter the human body. This meta-analysis aimed to evaluate current human epidemiological evidence on the relationship between PFAS exposure and glucolipid metabolism in childhood and adolescence. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases, and identified population-based epidemiological studies related to PFAS and glucolipid metabolism indexes that were published before 30 December 2022. The heterogeneity of the included literature was assessed using the I-square (I2) test and statistics Q. Random-effects and fixed-effects models were used to combine the effect size. Subgroup analysis based on age and sex of the study participants was performed. A sensitivity analysis was used to evaluate the robustness and reliability of the combined results. Egger's and Begg's tests were used to analyze publication bias. Results: A total of 12 studies were included in this analysis. There was a positive association between PFAS and TC (ß = 1.110, 95% CI: 0.601, 1.610) and LDL (ß = 1.900, 95% CI: 1.030, 2.770), and a negative association between PFAS and HOMA-IR in children and adolescents (ß = -0.130, 95% CI: -0. 200, -0.059). PFOS was significant positive associated with TC (ß = 8.22, 95% CI: 3.93, 12.51), LDL (ß = (12.04, 95% CI: 5.08, 18.99), and HOMA-IR (ß = -0.165, 95% CI: -0.292, -0.038). Subgroup analysis showed that exposure to PFAS in the adolescent group was positively associated with TC and LDL levels, and the relationship was stronger in females. Conclusion: PFAS exposure is associated with glucolipid metabolism in children and adolescents. Among them, PFOS may play an important role. Recognition of environmental PFAS exposure is critical for stabilizing the glycolipid metabolism relationship during the growth and development of children and adolescents.


Assuntos
Fluorocarbonos , Metabolismo dos Lipídeos , Adolescente , Criança , Feminino , Humanos , Bases de Dados Factuais , Fluorocarbonos/toxicidade , Homeostase , Reprodutibilidade dos Testes , Masculino
3.
J Pediatr Health Care ; 38(2): 184-193, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38429030

RESUMO

INTRODUCTION: This qualitative research study explored practices that support and advance diverse membership in Patient and Family Advisory Councils (PFACs) in children's hospitals and the involvement of PFACs in organization-level diversity, equity, and inclusion work. METHOD: This study consisted of a focused literature review and 17 key informant interviews. The study sought to identify important learnings about (1) recruiting and supporting patient and family advisors (PFAs) from historically marginalized populations and (2) ways to develop and sustain meaningful partnerships with PFAs and PFACs in diversity, equity, and inclusion work. RESULTS: The study findings highlighted a number of best practices for hospitals to adopt, including more actively reaching out to communities served, addressing barriers to participation through approaches and structures such as specialty PFACs and "tiered" options for participation by PFAs, and co-creation of inclusive environments. DISCUSSION: To move forward with this work, additional research, true commitment from health care organizations, and shared guidance and tools for the field are needed.


Assuntos
Diversidade, Equidade, Inclusão , Fluorocarbonos , Criança , Humanos , Comitês Consultivos , Pesquisa Qualitativa , Hospitais Pediátricos
4.
Transl Vis Sci Technol ; 13(3): 4, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466299

RESUMO

Purpose: The purpose of this study was to search for contaminants in silicone oil tamponades removed from eyes treated for retinal detachment, and to correlate chemical results with some clinical/functional parameters of the considered eyes. Methods: We examined a sequential cohort of eyes grouped according to the tamponade received: (1) Siluron2000 (S2), (2) RS-OIL ECS5000 (S5), and (3) Densiron Xtra (DX). Samples were collected at the beginning of the scheduled removal and analyzed by untargeted headspace gas-chromatography mass spectrometry (HS-GC-MS). Visual acuity and optic coherence tomography assessments were obtained before and after the tamponade removal. Results: Forty-one samples were analyzed: 22 belonging to the DX group, 13 to the S2 group, and 6 to the S5 group. For each group, a mixture of uninjected commercial preparation was analyzed as the reference. Different siloxanes and fluorinated compounds including perfluorodecalin (PFCL) were the most prevalent chemicals, found in 55% to 100% of the intraocular samples of the 3 groups. Some siloxanes were present also in the control matrices, whereas PFCL was only in the extracted tamponades. In the DX group, the concentration of hexamethylcyclotrisiloxane showed an inverse correlation trend with the duration of its permanence inside the eye (P = 0.054). Different alkanes, propanol, and acetaldehyde were identified only in the control matrices. Conclusions: Several contaminants including siloxanes were identified in the intraocular samples and in the control matrices. A time-related ocular uptake of some of these is conceivable. PFCL was also highly present but only in intraocular samples. Translational Relevance: After intraocular permanence silicone oils (SOs) have various unlabeled contaminants with some relevant differences with the commercial formulation chemical profile.


Assuntos
Fluorocarbonos , Descolamento Retiniano , Humanos , Descolamento Retiniano/cirurgia , Óleos de Silicone , Siloxanas , Olho
5.
Int J Popul Data Sci ; 9(1): 2180, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476271

RESUMO

Background: Aqueous film forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS) caused local environmental contamination in three Australian residential areas: Katherine in the Northern Territory (NT), Oakey in Queensland (Qld) and Williamtown in New South Wales (NSW). We examined whether children who lived in these areas had higher risks of developmental vulnerabilities than children who lived in comparison areas without known contamination. Methods: All children identified in the Medicare Enrolment File-a consumer directory for Australia's universal healthcare insurance scheme-who ever lived in exposure areas, and a sample of children who ever lived in selected comparison areas, were linked to the Australian Early Development Census (AEDC). The AEDC data were available from four cycles: 2009, 2012, 2015 and 2018. For each exposure area, we estimated relative risks (RRs) of developmental vulnerability on each of five AEDC domains and a summary measure, adjusting for sociodemographic characteristics and other potential confounders. Findings: We included 2,429 children from the NT, 2,592 from Qld and 510 from NSW. We observed lower risk of developmental vulnerability in the Communication skills and general knowledge domain in Katherine (RR = 0.74, 95% confidence interval (CI) 0.57 to 0.97), and higher risks of developmental vulnerability in the same domain (RR = 1.49, 95% CI 1.18 to 1.87) and in the Physical health and wellbeing domain in Oakey (RR = 1.31, 95% CI 1.06 to 1.61). Risks of developmental vulnerabilities on other domains were not different from those in the relevant comparison areas or were uncertain due to small numbers of events. Conclusion: There was inadequate evidence for increased risks of developmental vulnerabilities in children who ever lived in three PFAS-affected areas in Australia.


Assuntos
Fluorocarbonos , Programas Nacionais de Saúde , Idoso , Criança , Humanos , Risco , Desenvolvimento Infantil , Northern Territory
6.
Int J Mol Sci ; 25(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38473932

RESUMO

Per- and poly-fluoroalkyl substances (PFAS), such as GenX, are a class of highly stable synthetic compounds that have recently become the focus of environmental remediation endeavors due to their toxicity. While considerable strides have been made in PFAS remediation, the diversity of these compounds, and the costs associated with approaches such as ion exchange resins and advanced oxidation technologies, remain challenging for widespread application. In addition, little is known about the potential binding and impacts of GenX on human proteins. To address these issues, we applied phage display and screened short peptides that bind specifically to GenX, with the ultimate goal of identifying human proteins that bind with GenX. In this study we identified the amino acids that contribute to the binding and measured the binding affinities of the two discovered peptides with NMR. A human protein, ankyrin-repeat-domain-containing protein 36B, with matching sequences of one of the peptides, was identified, and the binding positions were predicted by docking and molecular dynamics simulation. This study created a platform to screen peptides that bind with toxic chemical compounds, which ultimately helped us identify biologically relevant molecules that could be inhibited by the GenX, and also provided information that will contribute to future bioengineered GenX-binding device design.


Assuntos
Bacteriófagos , Fluorocarbonos , Humanos , Peptídeos/química , Fluorocarbonos/metabolismo , Bacteriófagos/metabolismo
7.
J Physiol Sci ; 74(1): 15, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443820

RESUMO

Perfluorooctane sulfonate (PFOS) exerts adverse effects on neuronal development in young population. Limited evidences have shown that early-life PFOS exposure holds a potential risk for developing age-related neurodegenerative diseases such as Alzheimer's disease later in life. The present study investigated the effects of lactational PFOS exposure on cognitive function using one-year-old mice. Dams were exposed to PFOS (1 mg/kg body weight) through lactation by gavage. Male offspring were used for the behavior test battery to assess cognitive function. Western blot analysis was conducted to measure the levels of proteins related to the pathogenesis of Alzheimer's disease. PFOS-exposed mice displayed a mild deficiency in social recognition. In the hippocampus, the expression of tau protein was significantly increased. These results underline a mild effect of developing PFOS exposure on cognitive function and neurodegeneration. The present study presents the long-lasting effects of PFOS in middle-aged period and warrants a potential aftermath.


Assuntos
Ácidos Alcanossulfônicos , Doença de Alzheimer , Fluorocarbonos , Masculino , Feminino , Animais , Camundongos , Lactação , Fluorocarbonos/toxicidade , Hipocampo
8.
Water Environ Res ; 96(3): e11009, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444297

RESUMO

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are an emerging issue in wastewater treatment. High-temperature thermal processes, incineration being time-tested, offer the opportunity to destroy and change the composition of PFAS. The fate of PFAS has been documented through wastewater sludge incinerators, including a multiple hearth furnace (MHF) and a fluidized bed furnace (FBF). The dewatered wastewater sludge feedstock averaged 247- and 1280-µmol targeted PFAS per sample run in MHF and FBF feed, respectively. Stack emissions (reportable for all targeted PFAS from MHF only) averaged 5% of that value with shorter alkyl chain compounds comprising the majority of the targeted PFAS. Wet scrubber water streams accumulated nonpolar fluorinated organics from the furnace exhaust with an average of 0.740- and 0.114-mol F- per sample run, for the MHF and FBF, respectively. Simple alkane PFAS measured at the stack represented 0.5%-4.5% of the total estimated facility greenhouse gas emissions. PRACTITIONER POINTS: The MHF emitted six short chain PFAS from the stack, which were shorter alkyl chain compounds compared with sludge PFAS. The FBF did not consistently emit reportable PFAS from the stack, but contamination complicated the assessment. Five percent of the MHF sludge molar PFAS load was reported in the stack. MHF and FBF wet scrubber water streams accumulated nonpolar fluorinated organics from the furnace exhaust. Ultra-short volatile alkane PFAS measured at the stack represented 0.5%-4.5% of the estimated facility greenhouse gas emissions.


Assuntos
Fluorocarbonos , Gases de Efeito Estufa , Esgotos , Águas Residuárias , Alcanos , Incineração , Água
9.
Pestic Biochem Physiol ; 199: 105776, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458683

RESUMO

γ-Aminobutyric acid receptors (GABARs) are crucial targets for pest control chemicals, including meta-diamide and isoxazoline insecticides, which act as negative allosteric modulators of insect GABARs. Previous cell-based assays have indicated that amino acid residues in the transmembrane cavity between adjacent subunits of Drosophila RDL GABAR (i.e., Ile276, Leu280, and Gly335) are involved in mediating the action of meta-diamides. In this study, to confirm this result at the organismal level, we employed CRISPR/Cas9-mediated genome editing, generated six transgenic Drosophila strains carrying substitutions in these amino acid residues, and investigated their sensitivity to broflanilide and isocycloseram. Flies homozygous for the I276F mutation did not exhibit any change in sensitivity to the tested insecticides compared to the control flies. Conversely, I276C homozygosity was lethal, and heterozygous flies exhibited ∼2-fold lower sensitivity to broflanilide than the control flies. Flies homozygous for the L280C mutation survived into adulthood but exhibited infertility. Both heterozygous and homozygous L280C flies exhibited ∼3- and âˆ¼20-fold lower sensitivities to broflanilide and isocycloseram, respectively, than the control flies. The reduction in sensitivity to isocycloseram in L280C flies diminished to ∼3-fold when treated with piperonyl butoxide. Flies homozygous for the G335A mutation reached the adult stage. However, they were sterile, had small bodies, and exhibited reduced locomotion, indicating the critical role of Gly335 in RDL function. These flies exhibited markedly increased tolerance to topically applied broflanilide and isocycloseram, demonstrating that the conserved Gly335 is the target of the insecticidal actions of broflanilide and isocycloseram. Considering the significant fitness costs, the Gly335 mutation may not pose a serious risk for the development of resistance in field populations of insect pests. However, more careful studies using insect pests are needed to investigate whether our perspective applies to resistance development under field conditions.


Assuntos
Benzamidas , Proteínas de Drosophila , Fluorocarbonos , Inseticidas , Animais , Receptores de GABA/genética , Receptores de GABA/metabolismo , Drosophila/genética , Drosophila/metabolismo , Inseticidas/farmacologia , Inseticidas/química , Glicina/farmacologia , Mutagênese , Resistência a Inseticidas/genética , Receptores de GABA-A/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo
10.
Sci Rep ; 14(1): 5338, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438437

RESUMO

Pesticides are indispensable tools in modern agriculture for enhancing crop productivity. However, the inherent toxicity of pesticides raises significant concerns regarding human exposure, particularly among agricultural workers. This study investigated the exposure and associated risks of two commonly used pesticides in open-field pepper cultivation, namely, chlorothalonil and flubendiamide, in the Republic of Korea. We used a comprehensive approach, encompassing dermal and inhalation exposure measurements in agricultural workers during two critical scenarios: mixing/loading and application. Results revealed that during mixing/loading, dermal exposure to chlorothalonil was 3.33 mg (0.0002% of the total active ingredient [a.i.]), while flubendiamide exposure amounted to 0.173 mg (0.0001% of the a.i.). Conversely, dermal exposure increased significantly during application to 648 mg (chlorothalonil) and 93.1 mg (flubendiamide), representing 0.037% and 0.065% of the total a.i., respectively. Inhalation exposure was also evident, with chlorothalonil and flubendiamide exposure levels varying across scenarios. Notably, the risk assessment using the Risk Index (RI) indicated acceptable risk of exposure during mixing/loading but raised concerns during application, where all RIs exceeded 1, signifying potential risk. We suggest implementing additional personal protective equipment (PPE) during pesticide application, such as gowns and lower-body PPE, to mitigate these risks.


Assuntos
Fluorocarbonos , Nitrilas , Praguicidas , Ftalimidas , Piper nigrum , Sulfonas , Humanos , Fazendeiros , Medição de Risco , Benzamidas , Praguicidas/toxicidade
11.
Sci Total Environ ; 922: 171234, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38428612

RESUMO

As a ubiquitous pollutant in the environment, hexafluoropropylene oxide trimer acid (HFPO-TA) has been proven to have strong hepatotoxicity. However, the underlying mechanism is still unclear. Consequently, in vivo and in vitro models of HFPO-TA exposure were established to investigate the detrimental effects of HFPO-TA on the liver. In vivo, we discovered that HFPO-TA enhanced endoplasmic reticulum (ER)-mitochondrial association, caused mitochondrial oxidative damage, activated ER stress, and induced apoptosis in mouse livers. In vitro experiments confirmed that IP3R overexpression on ER structure increased mitochondrial calcium levels, which led to mitochondrial damage and mitochondria-dependent apoptosis in HepG2 cells exposed to HFPO-TA. Subsequently, damaged mitochondria released a large amount of mitochondrial ROS, which activated ER stress and ER stress-dependent apoptosis. In conclusion, this study demonstrates that HFPO-TA can induce apoptosis by regulating the crosstalk between ER and mitochondria, ultimately leading to liver damage. These findings reveal the significant hepatotoxicity of HFPO-TA and its potential mechanisms.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fluorocarbonos , Mitocôndrias , Propionatos , Animais , Camundongos , Apoptose , Retículo Endoplasmático/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo
12.
Sci Rep ; 14(1): 6501, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499613

RESUMO

The rapid screening of protein binding affinity for poly- and perfluoroalkyl substances (PFAS) benefits risk assessment and fate and transport modelling. PFAS are known to bioaccumulate in livestock through contaminated food and water. One excretion pathway is through milk, which may be facilitated by binding to milk proteins such as bovine serum albumin (BSA). We report a label-free differential scanning fluorimetry approach to determine PFAS-BSA binding over a broad temperature range. This method utilizes the tryptophan residue within the protein binding pocket as an intrinsic fluorophore, eliminating the need for fluorophore labels that may influence binding. BSA association constants were determined by (a) an equilibrium-based model at the melting temperature of BSA and (b) the Hill adsorption model to account for temperature dependent binding and binding cooperativity. Differences in binding between PFAS and fatty acid analogs revealed that a combination of size and hydrophobicity drives PFAS binding.


Assuntos
Fluorocarbonos , Soroalbumina Bovina , Soroalbumina Bovina/química , Fluorometria , Espectrometria de Fluorescência , Ligação Proteica , Fluorocarbonos/química
13.
Ecotoxicol Environ Saf ; 273: 116170, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452704

RESUMO

Perfluorooctanoic acid (PFOA), commonly found in drinking water, leads to widespread exposure through skin contact, inhalation, and ingestion, resulting in detectable levels of PFOA in the bloodstream. In this study, we found that exposure to PFOA disrupts cardiac function in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed reductions in field and action potentials in hiPSC-CMs exposed to PFOA. Furthermore, PFOA demonstrated a dose-dependent inhibitory effect on various ion channels, including the calcium, sodium, and potassium channels. Additionally, we noted dose-dependent inhibition of the expression of these ion channels in hiPSC-CMs following exposure to PFOA. These findings suggest that PFOA exposure can impair cardiac ion channel function and decrease the transcription of genes associated with these channels, potentially contributing to cardiac dysfunction such as arrhythmias. Our study sheds light on the electrophysiological and epigenetic consequences of PFOA-induced cardiac dysfunction, underscoring the importance of further research on the cardiovascular effects of perfluorinated compounds (PFCs).


Assuntos
Caprilatos , Fluorocarbonos , Cardiopatias , Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos , Canais Iônicos
14.
Ecotoxicol Environ Saf ; 273: 116173, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38452703

RESUMO

Per- and polyfluoroalkyl (PFAS) substances are enduring industrial materials. 17ß-Hydroxysteroid dehydrogenase isoform 1 (17ß-HSD1) is an estrogen metabolizing enzyme, which transforms estrone into estradiol in human placenta and rat ovary. Whether PFAS inhibit 17ß-HSD1 and what the structure-activity relationship (SAR) remains unexplored. We screened 18 PFAS for inhibiting human and rat 17ß-HSD1 in microsomes and studied their SAR and mode of action(MOA). Of the 11 perfluorocarboxylic acids (PFCAs), C8-C14 PFCAs at a concentration of 100 µM substantially inhibited human 17ß-HSD1, with order of C11 (half-maximal inhibition concentration, IC50, 8.94 µM) > C10 (10.52 µM) > C12 (14.90 µM) > C13 (30.97 µM) > C9 (43.20 µM) > C14 (44.83 µM) > C8 (73.38 µM) > others. Of the 7 per- and poly-fluorosulfonic acids (PFSAs), the potency was C8S (IC50, 14.93 µM) > C7S (80.70 µM) > C6S (177.80 µM) > others. Of the PFCAs, C8-C14 PFCAs at 100 µM markedly reduced rat 17ß-HSD1 activity, with order of C11 (IC50, 9.11 µM) > C12 (14.30 µM) > C10 (18.24 µM) > C13 (25.61 µM) > C9 (67.96 µM) > C8 (204.39 µM) > others. Of the PFSAs, the potency was C8S (IC50, 37.19 µM) > C7S (49.38 µM) > others. In contrast to PFOS (C6S), the partially fluorinated compound 6:2 FTS with an equivalent number of carbon atoms demonstrated no inhibition of human and rat 17ß-HSD1 activity at a concentration of 100 µM. The inhibition of human and rat enzymes by PFAS followed a V-shaped trend from C4 to C14, with a nadir at C11. Moreover, human 17ß-HSD1 was more sensitive than rat enzyme. PFAS inhibited human and rat 17ß-HSD1 in a mixed mode. Docking analysis revealed that they bind to the NADPH and steroid binding site of both 17ß-HSD1 enzymes. The 3D quantitative SAR (3D-QSAR) showed that hydrophobic region, hydrogen bond acceptor and donor are key factors in binding to 17ß-HSD1 active sites. In conclusion, PFAS exhibit inhibitory effects on human and rat 17ß-HSD1 depending on factors such as carbon chain length, degree of fluorination, and the presence of carboxylic acid or sulfonic acid groups, with a notable V-shaped shift observed at C11.


Assuntos
Fluorocarbonos , Relação Quantitativa Estrutura-Atividade , Gravidez , Feminino , Humanos , Animais , Ratos , Simulação de Acoplamento Molecular , 17-Hidroxiesteroide Desidrogenases/química , 17-Hidroxiesteroide Desidrogenases/metabolismo , Estrona , Carbono , Fluorocarbonos/toxicidade
15.
Int J Hyg Environ Health ; 257: 114346, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447259

RESUMO

BACKGROUND: Studies on cognitive and neurodevelopmental outcomes have shown inconsistent results regarding the association with prenatal exposure to perfluoroalkyl substance (PFAS) and organochlorines. Assessment of mixture effects of correlated chemical exposures that persist in later life may contribute to the unbiased evaluation and understanding of dose-response associations in real-life exposures. METHODS: For a subset of the 4th Flemish Environment and Health Study (FLEHS), concentrations of four PFAS and six organochlorines were measured in respectively 99 and 153-160 cord plasma samples and 15 years later in adolescents' peripheral serum by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Sustained and selective attention were measured at 14-15 years with the Continuous Performance Test (CPT) and Stroop Test as indicators of potential neurodevelopmental deficits. Quantile g-computation was applied to assess the joint associations between prenatal exposure to separate and combined groups of PFAS and organochlorines and performance in the CPT and Stroop Test at adolescence. Subsequently, individual effects of each chemical compound were analyzed in mixed effects models with two sets of covariates. Analytical data at birth and at the time of cognitive assessment allowed for off-setting postnatal exposure. RESULTS: In mixtures analysis, a simultaneous one-quantile increase in the natural log-transformed values of PFAS and organochlorines combined was associated with a decrease in the mean reaction time (RT) and the reaction time variability (RTV) in the CPT (ß = -15.54, 95% CI:-29.64, -1.45, and ß = -7.82, 95% CI: -14.97, -0.67 respectively) and for the mixture of PFAS alone with RT (ß = -11.94, 95% CI: -23.29, -0.60). In the single pollutant models, these results were confirmed for the association between perfluorohexanesulfonate (PFHxS) with RT (ß = -17.95, 95% CI = -33.35, -2.69) and hexachlorobenzene with RTV in the CPT (ß = -5.78, 95% CI: -10.39, -0.76). Furthermore, the participants with prenatal exposure above the limit of quantification for perfluorononanoic acid (PFNA) had a significantly shorter RT and RTV in the CPT (ß = -23.38, 95% CI: -41.55, -5.94, and ß = -9.54, 95% CI: -19.75, -0.43, respectively). CONCLUSION: Higher prenatal exposure to a PFAS mixture and a mixture of PFAS and organochlorines combined was associated with better sustained and selective attention during adolescence. The associations seemed to be driven by PFHxS and were not linked to exposure levels at the time of assessment.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Feminino , Gravidez , Recém-Nascido , Humanos , Adolescente , Cromatografia Líquida , Espectrometria de Massas em Tandem , Cognição
16.
Environ Health Perspect ; 132(2): 26001, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38319881

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) encompass a class of chemically and structurally diverse compounds that are extensively used in industry and detected in the environment. The US Environmental Protection Agency (US EPA) 2021 PFAS Strategic Roadmap describes national research plans to address the challenge of PFAS. OBJECTIVES: Systematic Evidence Map (SEM) methods were used to survey and summarize available epidemiological and mammalian bioassay evidence that could inform human health hazard identification for a set of 345 PFAS that were identified by the US EPA's Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing and through interagency discussions on PFAS of interest. This work builds from the 2022 evidence map that collated evidence on a separate set of ∼150 PFAS. Like our previous work, this SEM does not include PFAS that are the subject of ongoing or completed assessments at the US EPA. METHODS: SEM methods were used to search, screen, and inventory mammalian bioassay and epidemiological literature from peer-reviewed and gray literature sources using manual review and machine-learning software. For each included study, study design details and health end points examined were summarized in interactive web-based literature inventories. Some included studies also underwent study evaluation and detailed extraction of health end point data. All underlying data is publicly available online as interactive visuals with downloadable metadata. RESULTS: More than 13,000 studies were identified from scientific databases. Screening processes identified 121 mammalian bioassay and 111 epidemiological studies that met screening criteria. Epidemiological evidence (available for 12 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Mammalian bioassay evidence (available for 30 PFAS) commonly assessed effects in the reproductive, whole-body, nervous, and hepatic systems. Overall, 41 PFAS had evidence across mammalian bioassay and epidemiology data streams (roughly 11% of searched chemicals). DISCUSSION: No epidemiological and/or mammalian bioassay evidence were identified for most of the PFAS included in our search. Results from this SEM, our 2022 SEM on ∼150 PFAS, and other PFAS assessment products from the US EPA are compiled into a comprehensive PFAS dashboard that provides researchers and regulators an overview of the current PFAS human health landscape including data gaps and can serve as a scoping tool to facilitate prioritization of PFAS-related research and/or risk assessment activities. https://doi.org/10.1289/EHP13423.


Assuntos
Fluorocarbonos , Animais , Estados Unidos , Humanos , United States Environmental Protection Agency , Reprodução , Medição de Risco , Fluorocarbonos/toxicidade , Mamíferos
17.
Front Biosci (Landmark Ed) ; 29(2): 79, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38420806

RESUMO

BACKGROUND: Contaminants of emerging concern (CECs) have garnered significant attention due to their potential impacts on ecology, wildlife, and human health. The interest in these contaminants arises from their inadequate regulation or lack of routine monitoring in natural environments. Among them, per- and polyfluoroalkyl substances (PFAS) are of particular concern due to their notable propensity to accumulate within the kidney, significantly influencing the excretion of these pollutants. Rodlet cells (RCs) have emerged as promising indicators of immunotoxicity in response to chemical stressors. A prior comprehensive study extensively detailed the effects of sub-chronic exposure to perfluorooctanoic acid (PFOA), a well-known PFAS compound, on RCs located in the hematopoietic tissue of the common carp kidney. Even at concentrations commonly found in the environment, PFOA exhibited a significant impact on the distribution patterns of RCs, concurrently enhancing exocytosis activity. METHODS: The assessment of PFOA-induced RC degranulation employed texture analysis combined with linear discriminant analysis (LDA) to differentiate between various experimental exposure groups. The investigation encompassed three fish groups: an unexposed group, a group exposed to an environmentally relevant PFOA concentration (200 ng L-1), and a group exposed to a higher PFOA concentration (2 mg L-1). Texture analysis was conducted on high-resolution color (RGB) images obtained from light microscopy of ultrathin sections from five fish per experimental group, stained with toluidine blue. RESULTS: This analysis facilitated the quantification of potential cytoplasmic alterations associated with degranulation, encompassing all three RGB channels. The data subjected to LDA enabled the identification of the most distinctive texture characteristics, providing a reliable, objective, and reproducible method to differentiate between experimental groups. Remarkably, 98.0% of both the original and cross-validated cases were correctly classified. However, only one unexposed case was misclassified as a fish exposed to a 200 ng L-1 PFOA concentration, constituting the single false positive in the analysis. CONCLUSIONS: Utilizing texture analysis and LDA to quantify RC degranulation offers a dependable approach for assessing immunotoxicity within experimental models of toxicological and environmental pathology. This underscores the scientific significance of employing a morphological approach in such investigations.


Assuntos
Caprilatos , Poluentes Ambientais , Fluorocarbonos , Poluentes Químicos da Água , Animais , Humanos , Degranulação Celular , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Fluorocarbonos/toxicidade , Fluorocarbonos/análise
18.
J Hazard Mater ; 467: 133596, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38325097

RESUMO

Short-chain Perfluorinated compounds (PFCs), used as substitutes for highly toxic long-chain PFCs, are increasingly entering the aquatic environment. However, the toxicity of short-chain PFCs in the environment is still controversial. This study investigated the effects of short-chain perfluorobutanesulfonic acid (PFBS) at different concentrations (2.5, 6, 14.4, 36, and 90 mg/L) on M. aeruginosa growth under 12-day exposure and explored the molecular mechanism of toxicity using transcriptomics. The results showed that M. aeruginosa exhibited hormetic effects after exposure to PFBS. Low PFBS concentrations stimulated algal growth, whereas high PFBS concentrations inhibited it, and this inhibitory effect became progressively more pronounced with increasing PFBS exposure concentrations. Transcriptomics showed that PFBS promoted the pathways of photosynthesis, glycolysis, energy metabolism and peptidoglycan synthesis, providing the energy required for cell growth and maintaining cellular morphology. PFBS, on the other hand, caused growth inhibition in algae mainly through oxidative stress, streptomycin synthesis, and genetic damage. Our findings provide new insights into the toxicity and underlying mechanism of short-chain PFCs on algae and inform the understanding of the hormetic effect of short-chain PFCs, which are crucial for assessing their ecological risks in aquatic environments.


Assuntos
Fluorocarbonos , Microcystis , Ácidos Sulfônicos , Microcystis/genética , Ciclo Celular , Proliferação de Células , Metabolismo Energético
19.
Free Radic Biol Med ; 214: 173-183, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342163

RESUMO

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.


Assuntos
Lesões Encefálicas , Fluorocarbonos , Hipóxia Encefálica , Hemorragia Subaracnóidea , Animais , Humanos , Oxigênio , Fluorocarbonos/uso terapêutico , Hipóxia Encefálica/terapia
20.
Water Res ; 252: 121146, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306753

RESUMO

Nearly all per- and polyfluoroalkyl substances (PFAS) biotransformation studies reported to date have been limited to laboratory-scale batch reactors. The fate and transport of PFAS in systems that more closely represent field conditions, i.e., in saturated porous media under flowing conditions, remain largely unexplored. This study investigated the biotransformation of 6:2 fluorotelomer sulfonate (6:2 FTS), a representative PFAS of widespread environmental occurrence, in one-dimensional water-saturated flow-through columns packed with soil obtained from a PFAS-contaminated site. The 305-day column experiments demonstrated that 6:2 FTS biotransformation was rate-limited, where a decrease in pore-water velocity from 3.7 to 2.4 cm/day, resulted in a 21.7-26.1 % decrease in effluent concentrations of 6:2 FTS and higher yields (1.0-1.4 mol% vs. 0.3 mol%) of late-stage biotransformation products (C4C7 perfluoroalkyl carboxylates). Flow interruptions (2 and 7 days) were found to enhance 6:2 FTS biotransformation during the 6-7 pore volumes following flow resumption. Model-fitted 6:2 FTS column biotransformation rates (0.039-0.041 cmw3/gs/d) were ∼3.5 times smaller than those observed in microcosms (0.137 cmw3/gs/d). Additionally, during column experiments, planktonic microbial communities remained relatively stable, whereas the composition of the attached microbial communities shifted along the flow path, which may have been attributed to oxygen availability and the toxicity of 6:2 FTS and associated biotransformation products. Genus Pseudomonas dominated in planktonic microbial communities, while in the attached microbial communities, Rhodococcus decreased and Pelotomaculum increased along the flow path, suggesting their potential involvement in early- and late-stage 6:2 FTS biotransformation, respectively. Overall, this study highlights the importance of incorporating realistic environmental conditions into experimental systems to obtain a more representative assessment of in-situ PFAS biotransformation.


Assuntos
Fluorocarbonos , Microbiota , Poluentes Químicos da Água , Fluorocarbonos/análise , Biotransformação , Alcanossulfonatos/metabolismo , Água , Poluentes Químicos da Água/análise
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