Metabolic characteristics and pathogenesis of precocious puberty in girls: the role of perfluorinated compounds.

BACKGROUND: Precocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP. METHODS: Nuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP. RESULTS: The disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT. CONCLUSIONS: The elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.

Locally caught freshwater fish across the United States are likely a significant source of exposure to PFOS and other perfluorinated compounds.

Per- and polyfluoroalkyl substances, or PFAS, gained significant public and regulatory attention due to widespread contamination and health harms associated with exposure. Ingestion of PFAS from contaminated food and water results in the accumulation of PFAS in the body and is considered a key route of human exposure. Here we calculate the potential contribution of PFOS from consumption of locally caught freshwater fish to serum levels. We analyzed data for over 500 composite samples of fish fillets collected across the United States from 2013 to 2015 under the U.S. EPA's monitoring programs, the National Rivers and Streams Assessment and the Great Lakes Human Health Fish Fillet Tissue Study. The two datasets indicate that an individual's consumption of freshwater fish is potentially a significant source of exposure to perfluorinated compounds. The median level of total targeted PFAS in fish fillets from rivers and streams across the United States was 9,500 ng/kg, with a median level of 11,800 ng/kg in the Great Lakes. PFOS was the largest contributor to total PFAS levels, averaging 74% of the total. The median levels of total detected PFAS in freshwater fish across the United States were 278 times higher than levels in commercially relevant fish tested by the U.S. Food and Drug Administration in 2019-2022. Exposure assessment suggests that a single serving of freshwater fish per year with the median level of PFAS as detected by the U.S. EPA monitoring programs translates into a significant increase of PFOS levels in blood serum. The exposure to chemical pollutants in freshwater fish across the United States is a case of environmental injustice that especially affects communities that depend on fishing for sustenance and for traditional cultural practices. Identifying and reducing sources of PFAS exposure is an urgent public health priority.

Environmental explanation of prostate cancer progression based on the comprehensive analysis of perfluorinated compounds.

Perfluorinated compounds (PFCs) are man-made chemicals used in the manufacture of many products with water and dirt repellent properties. Many diseases have been proved to be related to the exposure of PFCs, including breast fibroadenoma, hepatocellular carcinoma, breast cancer and leydig cell adenoma. However, whether the PFCs promote the progression of prostate cancer remains unclear. In this work, through comprehensive bioinformatics analysis, we discovered the correlation between the prostate cancer and five PFCs using Comparative Toxicogenomics Database (CTD), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, further analysis showed that several PFCs-related genes demonstrated strong prognostic value for prostate cancer patients. The survival analysis and receiver operating characteristic (ROC) curves revealed that PFCs-related genes based prognostic model held great predictive value for the prognosis of prostate cancer, which could potentially serve as an independent risk factor in the future. In vitro experiments verified the promotive role of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) in the growth of prostate cancer cells. This study provided novel insights into understanding the role of PFCs in prostate cancer and brought attention to the environmental association with cancer risks and progression.

Effects of perfluorinated compounds homologues on chemical property, microbial composition, richness and diversity of urban forest soil.

Perfluorinated compounds (PFCs), as an important class of new persistent organic pollutants, are widely distributed in the environment. Yet the effects of different types and concentrations of PFCs on soil microbial community in urban forest ecosystems are remain uncertain. Here, two typical PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were selected to carry out a pot experiment in greenhouse with singly and joint treatment at different concentrations, to examine their effects on composition and diversity of soil microorganisms and availability of soil macronutrients by using high-throughput Illumina sequencing approach. The results showed both PFOA and PFOS application significantly increased soil NO3--N and NH4+-N content, but did not alter total phosphorus content, compared to the control check (CK) treatments. Total potassium content was reduced in PFOA treatments but increased in PFOS and PFOA×PFOS treatments. The most dominant bacterial phylum was Chloroflexi in low and medium PFCs concentrations and the CK treatments, but it was switched to Acidobacteria in high concentrations. No obvious change was detected for the composition of the dominant fungi community in PFCs treatments compared to the CK treatments. With the increase of PFCs concentrations, soil bacterial richness decreased but its diversity increased, whereas the richness and diversity of fungal community usually decreased. Redundancy analyses revealed that soil fungal community was more sensitive to PFCs pollutants than soil bacterial communities. Further data analysis revealed by structural equation model (SEM) that the PFCs exposed for 60 days indirectly affects the diversity and richness of soil bacteria and fungi by directly affecting NO3--N and NH4+-N content. The results suggested the concentration of PFCs pollutants played a primary role in determining the composition, richness and diversity of forest soil microbial communities.

Replacement per- and polyfluoroalkyl substances (PFAS) are potent modulators of lipogenic and drug metabolizing gene expression signatures in primary human hepatocytes.

Per- and polyfluoroalkyl substances (PFAS) are a class of environmental toxicants, and some, such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), have been associated with hepatic steatosis in rodents and monkeys. It was hypothesized that perfluorosulfonic acids (C4, 6, 8), perfluorocarboxylic acids (C4-14), perfluoro(2-methyl-3-oxahexanoic) acid (HFPO-DA), 1H, 1H, 2H, 2H-perfluorooctanesulfonic acid (6:2 FTS) along with 3 PFOS precursors could induce expression of lipid metabolism genes and lipid deposition in human hepatocytes. Five-donor pooled cryopreserved human hepatocytes were cultured and treated with 0.1% DMSO vehicle or various PFAS (0.25 to 25 µM) in media. After a 48-h treatment, mRNA transcripts related to lipid transport, metabolism, and synthesis were measured using a Quantigene Plex assay. After 72-h treatments, hepatocytes were stained with Nile Red dye to quantify intracellular lipids. Overall, PFAS were transcriptionally active at 25 µM. In this model, lipid accumulation was not observed with C8-C12 treatments. Shorter chain PFAS (C4-C5), 6:2 FTS, and PFOS precursor, metFOSA, induced significant liver lipid accumulation, and gene activation at lower concentrations than legacy PFAS. In summary short chain PFAS and other alternative PFAS were more potent gene inducers, and potential health effects of replacement PFAS should be critically evaluated in humans.

Perfluorinated compounds (PFCs) in regional industrial rivers: Interactions between pollution flux and eukaryotic community phylosymbiosis.

Perfluorinated compounds (PFCs) pose serious threats to aquatic ecosystems, especially their microbial communities. However, little is known about the phylosymbiosis of aquatic fungal and viridiplantae communities in response to PFC accumulation. We quantified the distribution of 14 PFCs in rivers and found that PFBA was dominant in the transition from water to sediment. High through-put sequencing revealed that phyla Ascomycota, Basidiomycota, Anthophyta, and Chlorophyta were the predominant in eukaryotic community. The effects of PFCs on spatial community coalescence at taxonomic and phylogenetic levels (p < 0.05) were revealed. Fungal community coalescence triggered the spatial assembly of fungal and viridiplantae communities in riverine environments (p < 0.05). Null modeling indicated that PFBA, PFTrDA and PFOS, etc, mediated phylogenetic assembly (p < 0.05) and stochastic processes (86.67-100%) maintain phylogenetic turnover in the fungal community. Meanwhile, variable selection (27.78-54.44%) explained the viridiplantae community assemblage. Finally, we identified fungal genera Hannaella, Naganishia, Purpureocillium and Stachybotrys as indicators for PFC pollution (p < 0.001). These results help explain the effects of PFCs on riverine ecological remediation.

Framework for risk assessment of PFAS utilizing experimental studies and in-silico models.

Perfluoroalkyl substances (PFAS), especially PFOS and PFOA, are two widely used synthetic chemicals that can impact human health based on evidence from animal and epidemiologic studies. In this paper, we have reviewed and summarized the influence of PFAS exposure on health, pointing the quality of evidence, and applied translational techniques to integrate evidence for PFAS policy making. This is the first review where highly referred articles on PFAS used for policymaking by several regulatory agencies were collected and evaluated based on the review guidelines developed by the US National Toxicology Program's Office of Health Assessment and Translation (OHAT) review guidelines. Several limitations were observed, including co-exposure to multiple chemicals and limited measurement of primary and secondary outcomes related to specific toxicity. However, data from all the studies provided a moderate to strong level of confidence for link between PFAS exposure and different adverse outcomes. Secondly, for translating the risk to humans, an in-silico model and scaling approach was utilized. Physiologically based pharmacokinetic model (PBPK) was used to calculate the human equivalent dose (HED) from two widely accepted studies and compared with tolerable daily intakes (TDIs) established by various regulatory agencies. Inter-species dose extrapolation was done to compare with human the relevance of dosing scenarios used in animals. Overall, a framework for translation of risk was proposed based on the conclusions of this review with the goal of improving policymaking. The current paper can improve the methodological protocols for PFAS experimental studies and encourage the utilization of in-silico models for translating risk.

Individual and mixture associations of perfluoroalkyl substances on liver function biomarkers in the Canadian Health Measures Survey.

BACKGROUND: Perfluoroalkyl substances can disrupt hepatic metabolism and may be associated with liver function biomarkers. We examined individual and mixture associations of PFAS on liver function biomarkers in a representative sample of Canadian adults. We explored the potential for effect modification by sex and body mass index, as well as by physical activity level which may attenuate the deleterious effect of PFAS on metabolic disorders. METHODS: We analyzed data from participants aged 20-74 from the Canadian Health Measures Survey. We used linear regression to examine associations between plasma concentrations of PFOA, PFOS, PFHxS, PFNA, PFDA, and PFUDA on serum concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin. We used quantile g-computation to estimate associations with a PFAS mixture for each simultaneous, one-quartile change in PFAS concentrations. RESULTS: Each doubling of PFOA, PFOS, PFHxS, or PFNA concentrations was associated with higher AST, GGT, and ALP concentrations. Each doubling of PFOA concentrations was associated with 16.5% (95%CI: 10.4, 23.0) higher GGT concentrations among adults not meeting Canada's physical activity guidelines vs. 6.6% (95%CI: -1.6, 15.5) among those meeting these guidelines. Sex and BMI also modified some associations, though to a lesser extent. We did not observe associations between ALT and PFOA (1.2% change; 95%CI: -2.5, 4.9), PFOS (2.2% change; 95%CI: -0.8, 5.3), or PFHxS (1.5% change; 95%CI: -0.4, 3.4). We also did not observe consistent associations for PFDA and PFUDA or with total bilirubin. In quantile g-computation models, each simultaneous one-quartile increase in the PFAS mixture was positively associated with AST (7.5% higher; 95%CI: 4.0, 10.4), GGT (9.7% higher; 95%CI: 1.7, 17.0), and ALP (2.8% higher; 95%CI: 0.5, 5.4). CONCLUSION: Higher plasma concentrations of PFOA, PFOS, PFHxS, and PFNA - both individually and as a mixture - were associated with higher serum concentrations of liver function biomarkers. These results contribute to emerging evidence suggesting that higher levels of physical activity appear to be protective against the hepatotoxic effects of PFOA. This work contributes to a growing body of evidence supporting the hepatotoxic effects of PFAS.

The comprehensive analysis based study of perfluorinated compounds-Environmental explanation of bladder cancer progression.

Perfluorinated compounds are emerging organic pollutants widely used in building materials, textiles, and electric equipment. Herein, silico analysis was conducted using bioinformatics approach to assess the potential relationship between bladder cancer and perfluorinated compounds. Transcriptome profiles and data of perfluorinated compounds were obtained from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression and Comparative Toxicogenomics databases. Gene Ontology (GO9 and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that interactive genes were mainly enriched in bladder cancer (BC). Transcriptome profiles were used to verify the expression of m6A-related genes at the mRNA and protein levels. Most m6A-related genes predicted BC prognosis. Survival analysis and ROC curves demonstrated that the expression levels of m6A-related genes were associated with BC prognosis. Perfluorooctanoic acid (PFOA) significantly increased the cell proliferation ability and promoted cell invasion capacity. In addition, PFOA significantly increased the cell viability and cell invasion capacity of T24 and BIU-87 cell lines compared with the control group. Taken together, these results show that perfluorinated compounds could promote BC progression. DATA AVAILABILITY: Data and materials are available within the manuscript.

Associations of Prenatal Exposure to Per- and Polyfluoroalkyl Substances with the Neonatal Birth Size and Hormones in the Growth Hormone/Insulin-Like Growth Factor Axis.

Toxicological data suggest a significant developmental toxicity of per- and polyfluoroalkyl substances (PFASs); however, evidence in humans remains inconclusive. Furthermore, the effects of prenatal exposure to PFASs on hormones in the growth hormone (GH)/insulin-like growth factor (IGF) axis of newborns remain largely unclear. We aimed to investigate the associations of prenatal exposure to PFASs with the neonatal birth size, GH, IGF-1, and IGF-binding protein 3 (IGFBP-3). The concentrations of 22 PFASs were measured in the plasma of 224 pregnant women collected within 3 days before delivery (39.3 weeks) in Guangzhou, China, and the anthropometric data were gathered from medical records. Paired cord blood was collected at delivery to determine GH, IGF-1, and IGFBP-3 levels. Multivariable linear regression models revealed the inverse associations of several long-chain PFASs with birth weight and ponderal index as well as the significant associations of perfluorobutanoic acid and perfluorooctanoic acid (PFOA) with IGFBP-3 levels. The Bayesian kernel machine regression confirmed the association of perfluorooctane sulfonate with birth weight and ponderal index and of PFOA with IGFBP-3 and identified an inverse joint effect of exposure to a mixture of multiple PFASs on birth weight. The findings provide the first comprehensive evidence on the individual and joint effects of multiple PFASs on the neonatal birth size and hormones in the GH/IGF axis, which requires further confirmation.

Variety-Selective Rhizospheric Activation, Uptake, and Subcellular Distribution of Perfluorooctanesulfonate (PFOS) in Lettuce (Lactuca sativa L.).

Perfluorooctanesulfonate (PFOS) as an accumulative emerging persistent organic pollutant in crops poses severe threats to human health. Lettuce varieties that accumulate a lower amount of PFOS (low-accumulating crop variety, LACV) have been identified, but the regarding mechanisms remain unsolved. Here, rhizospheric activation, uptake, translocation, and compartmentalization of PFOS in LACV were investigated in comparison with those of high-accumulating crop variety (HACV) in terms of rhizospheric forms, transporters, and subcellular distributions of PFOS. The enhanced PFOS desorption from the rhizosphere soils by dissolved organic matter from root exudates was observed with weaker effect in LACV than in HACV. PFOS root uptake was controlled by a transporter-mediated passive process in which low activities of aquaporins and rapid-type anion channels were corrected with low expression levels of PIPs (PIP1-1 and PIP2-2) and ALMTs (ALMT10 and ALMT13) genes in LACV roots. Higher PFOS proportions in root cell walls and trophoplasts caused lower root-to-shoot transport in LACV. The ability to cope with PFOS toxicity to shoot cells was poorer in LACV relative to HACV since PFOS proportions were higher in chloroplasts but lower in vacuoles. Our findings provide novel insights into PFOS accumulation in lettuce and further understanding of multiprocess mechanisms of LACV.

Comprehensive Understanding of Fluoroacetate Dehalogenase-Catalyzed Degradation of Fluorocarboxylic Acids: A QM/MM Approach.

Fluorochemicals are persistent, bioaccumulative, and toxic compounds that are widely tributed in the environment. Developing efficient biodegradation strategies to decompose the fluorochemicals via breaking the inert C-F bonds presents a holistic challenge. As a promising biodegradation enzyme candidate, fluoroacetate dehalogenase (FAcD) has been reported as the only non-metallic enzyme to catalyze the cleavage of the strong C-F bond. Here, we systematically investigated the catalytic actions of FAcD toward its natural substrate fluoroacetate using molecular dynamics simulations and quantum mechanism/molecular mechanism calculations. We propose that the enzymatic transformation involves four elementary steps, (I) C-F bond activation, (II) nucleophilic attack, (III) C-O bond cleavage, and (IV) proton transfer. Our results show that nucleophilic attack is the rate-determining step. However, for difluoroacetate and trifluoroacetate, C-F bond activation, instead of nucleophilic attack, becomes the rate-determining step. We show that FAcD, originally recognized as α-fluorocarboxylic acid degradation enzyme, can catalyze the defluorination of difluoroacetate to glyoxylate, which is captured by our high-resolution mass spectrometry experiments. In addition, we employed amino acid electrostatic analysis method to screen potential mutation hotspots for tuning FAcD's electrostatic environment to favor substrate conversion. The comprehensive understanding of catalytic mechanism will inform a rational enzyme engineering strategy to degrade fluorochemicals for benefits of environmental sustainability.

Consumption of freshwater fish: A variable but significant risk factor for PFOS exposure.

PFOS, PFOA, PFNA and PFHxS are the PFAS substances that currently contribute most to human exposure, and in 2020 the European Food Safety Authority (EFSA) presented a draft opinion on a tolerable intake of 8 ng/kg/week for the sum of these four substances (equaling 0.42 µg/kg if expressed as an annual dose). Diet is usually the dominating exposure pathway, and in particular the intake of PFOS has been shown to be strongly related to the consumption of fish and seafood. Those who eat freshwater fish may be especially at risk since freshwater and its biota typically display higher PFOS concentrations than marine systems. In this study, we estimated the range in PFOS intake among average Swedish "normal" and "high" consumers of freshwater fish. By average we mean persons of average weight who eat average-sized portions. The "normal consumers" were assumed to eat freshwater fish 3 times per year, and the "high consumers" once a week. Under these assumptions, the yearly tolerable intake for "normal" and "high" consumers is reached when the PFOS concentrations in fish equals 59 and 3.4 µg per kg fish meat. For this study, PFOS concentrations in the muscle tissue of edible-sized perch, pike and pikeperch were retrieved from three different Swedish datasets, covering both rural and urban regions and a total of 78 different inland waters. Mean PFOS concentrations in fish from these sites varied from 0.3 to 750 µg/kg. From the available data, the annual min-max dietary PFOS intake for male "normal consumers" was found to be in the range 0.0021-5.4 µg/kg/yr for the evaluated scenarios, with median values of 0.02-0.16 µg/kg/yr. For male "high consumers", the total intake range was estimated to be 0.04-93 µg/kg/yr, with median values being 0.27-1.6 µg/kg/yr. For women, the exposure estimates were slightly lower, about 79% of the exposure in men. Despite highly variable PFOS concentrations in fish from different sites, we conclude that the three most commonly consumed freshwater species in Sweden constitute an important source for the total annual intake even for people who eat this kind of fish only a few times per year. The analyses of PFOA, PFNA and PFHxS showed values which were all below detection limit, and their contribution to the total PFAS intake via freshwater fish consumption is negligible in comparison to PFOS.

Per- and polyfluoroalkyl substances (PFAS) as contaminants of emerging concern in Asia's freshwater resources.

The occurrence of per- and polyfluoroalkyl substances (PFAS) in water resources is an emerging concern because of their environmental persistence and bioaccumulation in humans. In Western countries, health advisories regarding PFAS exposure have been released to warn the public of its potential adverse effects. However, awareness regarding PFAS exposure in Asia is still at its infancy as reflected by the minimal safeguards imposed to protect the population from exposure. Here, we reviewed studies on PFAS contamination in Asia with a focus on freshwater resources to determine whether PFAS is also a concern in this part of the globe. Peer reviewed articles which included information on PFAS levels from 2000 to 2020 were compiled. The highest PFAS contamination was detected in surface water relative to ground, tap, and drinking water. PFAS levels in water resources in several countries in Asia, such as China, Japan, and South Korea, were above the recommended level, similar to that in the United States. PFAS in South and Southeast Asia were just below the recommended level, but the rise of PFAS in China in the recent decade, alongside its remarkable economic and industrial growth, suggests that increased PFAS contamination in South and Southeast Asia may soon follow, as these countries compete with the global economy. Hence, there is a need for these countries to also implement measures that will reduce the exposure of their population to PFAS.

Perfluorinated compounds in a river basin from QingHai-Tibet Plateau: Occurrence, sources and key factors.

The occurrence of perfluorinated compounds (PFCs) in different environmental media in the QingHai-Tibet Plateau has been limitedly investigated. In this study, the water, sediments, soils and agricultural product samples were collected in the Huangshui River basin, and contents of the PFCs and values of water parameters were determined. This study investigated dominantly regulating factors of the distribution of PFCs in the water emphatically, explored the sources and assessed potential risks of the PFCs integrally. The results showed that perfluorohexanesulfonic acid, perfluorooctanesulfonic acid, perfluorobutanoic acid (PFBA) and perfluorooctanoic acid presented high maximum concentrations of 3207.42, 3015.96, 1941.89 and 826.4 ng L-1 in the water, respectively. There were 12 PFCs detected in crops, with the maximum concentration of 5206.86 ng g-1 for PFBA. The significantly positive correlation (p < 0.05) was observed between the concentrations of PFBA in crops and that in adjacent rivers, indicating that the irrigation most likely contributed to the accumulation of PFBA in the studied crops. The occurrence of the PFCs in the water during the dry season was dominantly regulated by fluorescent dissolved organic matters via the hydrophobic interaction, while it was primarily regulated by the total nitrogen and electrical conductivity via electrostatic interaction during the wet season. The PFCs in the water were mainly from the wastewater discharged from wastewater treatment plants and carpet factories, while the resuspension of the PFCs in sediments was also an important contribution especially in wet season. The PFCs in the river has posed sustained risk to the public health, especially children.

Perfluorinated compounds disrupted osmoregulation in Oryzias melastigma during acclimation to hypoosmotic environment.

Perfluorinated compounds (PFCs) are a type of ubiquitous contaminants spreading in the estuarine and coastal areas. Anadromous fish should deal with hypoosmotic challenge with PFCs stress during their migration from seawater to estuaries. However, few studies have been carried out to investigate the adverse impact of PFCs on fish osmoregulation and the underlying mechanism. In this study, Oryzias melastigma, an euryhaline fish model, were exposed to four representative PFC congeners including perfluorobutane sulfonate (PFBS), perfluorooctane sulfonates (PFOS), perfluorooctanoic acid (PFOA), and perfluorododecanoic acid (PFDoA) separately under both seawater and freshwater conditions. Histopathological changes in gills, ion homeostasis, Na+/K+-ATPase (NKA) activity, as well as the expression of related genes was detected upon exposure. Results showed that PFCs induced morphological changes in gills, disturbed the levels of major ions (Na+, Ca2+, Mg2+), and inhibited the NKA activity. Transcriptome analysis in fish gills during the acclimation to freshwater revealed that PFCs influenced the osmoregulation mainly by interfering with the endocrine system, signal transduction, as well as cellular community and motility. Validation with qRT-PCR confirmed that the mRNA expressions of osmoregulatory genes encoding hormones and receptors, as well as ion transmembrane transporters were disturbed by PFCs. Longer chain homolog (PFOS) showed a greater impact on osmoregulation than the shorter chain homolog (PFBS). Within the same carbon chain, sulfonic congener (PFOS) induced more serious injury to gills than carboxylic congener (PFOA). The interaction between PFCs and salinity varied in different adverse outcome. These results help to further understand the mechanism of how PFCs influence osmoregulation and elicit the need to assess the ecological risk of PFCs and other pollutants on anadromous migration.

Bioaccumulation, Biodistribution, Toxicology and Biomonitoring of Organofluorine Compounds in Aquatic Organisms.

This review is a survey of recent advances in studies concerning the impact of poly- and perfluorinated organic compounds in aquatic organisms. After a brief introduction on poly- and perfluorinated compounds (PFCs) features, an overview of recent monitoring studies is reported illustrating ranges of recorded concentrations in water, sediments, and species. Besides presenting general concepts defining bioaccumulative potential and its indicators, the biodistribution of PFCs is described taking in consideration different tissues/organs of the investigated species as well as differences between studies in the wild or under controlled laboratory conditions. The potential use of species as bioindicators for biomonitoring studies are discussed and data are summarized in a table reporting the number of monitored PFCs and their total concentration as a function of investigated species. Moreover, biomolecular effects on taxonomically different species are illustrated. In the final paragraph, main findings have been summarized and possible solutions to environmental threats posed by PFCs in the aquatic environment are discussed.

[Study on the Analytical Method of Solid Phase Extraction-Ultra Performance Liquid Chromatography Tandem Quadrupole Linear Ion Trap Mass Spectrometry for 12 Perfluorinated Compounds in Human Urine].

OBJECTIVE: To establish a method for simultaneous determination of 12 kinds of perfluorinated compounds (PFCs) in human urine based on ultra performance liquid chromatography tandem quadrupole linear ion trap mass spectrometry (UPLC-QTtrap-MS). METHODS: After pH adjustment with 2% formic acid, the urine samples were loaded on a WAX solid phase extraction (SPE) cartridge for extraction, purification and concentration. The eluates were collected, concentrated to dryness under nitrogen, and reconstituted with 10 mmol/L ammonium acetate aqueous solution-methanol ( V water∶ V methanol = 70∶30) before injection. UPLC was performed on a C 18 cartridge, and methanol and 10 mmol/L ammonium acetate aqueous solution was used as mobile phases with gradient elution. QTtrap-MS was operated in multiple reaction monitoring (MRM) mode, and the internal standard calibration curves were applied for quantitative analysis. RESULTS: Good linearity was obtained in the linear range, with the method detection limits and method quantification limits being 0.032 ng/L-6.5 ng/L and 0.10 ng/L-21 ng/L, respectively, for the 12 kinds of PFCs. The spiked recoveries of the 12 kinds of PFCs were 91.5%-114%, with the intra-day precision and the inter-day precision being 0.57%-16.0% and 1.88%-20.1%, respectively. The established method was applied to the determination of 12 kinds of PFCs in the urine samples of primary school students collected in one area. Nine kinds of PFCs were detected in the urine samples in this area. Among the PFCs detected, perfluorobutanesulfonic acid (PFBS) and perfluorooctanoic acid (PFOA) were the main PFCs found in the student urine samples. CONCLUSION: The method established in this study could be used to simultaneously examine 12 kinds of PFCs in urine. The method combined SPE with isotope internal standard correction and achieved good sensitivity and accuracy.

Perfluorooctanesulfonic acid (PFOS) administration shifts the hepatic proteome and augments dietary outcomes related to hepatic steatosis in mice.

Hepatic steatosis increases risk of fatty liver and cardiovascular disease. Perfluorooctanesulfonic acid (PFOS) is a persistent, bio-accumulative pollutant that has been used in industrial and commercial applications. PFOS administration induces hepatic steatosis in rodents and increases lipogenic gene expression signatures in cultured hepatocytes. We hypothesized that PFOS treatment interferes with lipid loss when switching from a high fat diet (HFD) to a standard diet (SD), and augments HFD-induced hepatic steatosis. Male C57BL/6 N mice were fed standard chow diet or 60% kCal high-fat diet (HFD) for 4 weeks to increase body weight. Then, some HFD mice were switched to SD and mice were further divided to diet only or diet containing 0.0003% PFOS, for six treatment groups: SD, HFD to SD (H-SD), HFD, SD + PFOS, H-SD + PFOS, or HFD + PFOS. After 10 weeks on study, blood and livers were collected. HFD for 14 weeks increased body weight and hepatic steatosis, whereas H-SD mice returned to SD measures. PFOS administration reduced body weight in mice fed a SD, but not H-SD or HFD. PFOS administration increased liver weight in H-SD + PFOS and HFD + PFOS mice. PFOS increased hepatic steatosis in H-SD and HFD groups. Hepatic mRNA expression and SWATH-MS proteomic analysis revealed that PFOS induced lipid and xenobiotic transporters, as well as metabolism pathways. Overall, the findings herein suggest that PFOS treatment did interfere with lipid loss associated with switch to a SD and similarly augmented hepatic lipid accumulation in mice established on an HFD.

Environmental Risk Assessment Resulting from Sediment Contamination with Perfluoroalkyl Substances.

Due to wide use of perfluoroalkyl substances (PFASs) (e.g., in metal-plating, in fire-fighting foam, lubricants) and their resistance to degradation, they occur widely in the environment. The aim of this study was to estimate the environmental risk resulting from the presence of PFASs in the Gulf of Gdansk. Therefore, 17 PFASs concentrations were determined using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Additionally, sediment ecotoxicity was investigated. The results of the chemical analysis were used to asses environmental risk of PFASs. In samples collected around discharge collectors from a wastewater treatment plant and the Vistula mouth, Σ17PFASs values were 0.00403 ÷ 40.6 and 0.509 ÷ 614 ng/g d.w., respectively. In samples collected around discharge collectors, PFHxA, PFPeA, PFHpA, and PFOA were dominating, while at the Vistula River mouth, PFHxS, PFDS, and PFBS were prevalent. For most sediments, no toxic effect was observed in the toxicity tests with Heterocypris inconguens and Aliivibrio ficsheri. There was no observed correlation between the PFASs level and their ecotoxicity. Generally, the results of environmental risk assessment indicate that the PFASs would not generate high impact on the aquatic life (five water samples have shown medium risk related to PFBS and PFDoA).