Uncovering Novel Per- and Polyfluoroalkyl Substances (PFAS) with Non-Targeted Ion Mobility Spectrometry-Mass Spectrometry Analyses
Ontology highlight
ABSTRACT:
INSTRUMENT(S): 6560 Q-TOF LC/MS
ORGANISM(S): Environmental Samples <bacillariophyta> (ncbitaxon:33858)
SUBMITTER: 
Erin Baker
PROVIDER: MSV000091638 | MassIVE | Tue Apr 04 14:19:00 BST 2023
REPOSITORIES: MassIVE
Similar Datasets
Project description:The use of aqueous film-forming foams (AFFF) at fire-training areas (FTAs) has introduced into ground- and surface waters a complex mixture of per- and poly-fluorinated alkyl substances (PFAS). The toxicity of environmental PFAS mixtures to wildlife is not well understood and presents a knowledge gap that limits accurate risk assessment. To evaluate reproductive biomarker responses to complex environmental PFAS mixtures, we conducted a series of on-site experiments using flow-through mobile laboratories exposing fish to groundwater impacted by a legacy FTA and an adjacent reference site A 60K fathead minnow microarray was used to quantify gene expression patterns in the testis and liver of fish exposed to water from Fire Training Area 1 and 2 relative to a reference site.
2024-08-31 | GSE261669 | GEO
Project description:The use of aqueous film-forming foams (AFFF) at fire-training areas (FTAs) has introduced into ground- and surface waters a complex mixture of per- and poly-fluorinated alkyl substances (PFAS). The toxicity of environmental PFAS mixtures to wildlife is not well understood and presents a knowledge gap that limits accurate risk assessment. To evaluate reproductive biomarker responses to complex environmental PFAS mixtures, we conducted a series of on-site experiments using flow-through mobile laboratories exposing fish to groundwater impacted by a legacy FTA and an adjacent reference site A 60K fathead minnow microarray was used to quantify gene expression patterns in the testis and liver of fish exposed to water from Fire Training Area 1 and 2 relative to a reference site.
2024-08-31 | GSE261668 | GEO
Project description:Per- and polyfluoroalkyl substances (PFAS) are a diverse family of industrially significant synthetic chemicals infamous for extreme environmental persistence and global environmental distribution. Many PFAS are bioaccumulative and biologically active mainly due to their tendency to bind with various proteins. These protein interactions may be the most important element in determining the accumulation potential and tissue distribution of individual PFAS. Trophodynamics studies including aquatic food webs present inconsistent evidence for PFAS biomagnification. This study strives to identify whether the observed variability in PFAS bioaccumulation potential among species could correspond with interspecies protein composition differences. Specifically, this work compares the perfluorooctane sulfonate (PFOS) serum protein binding potential and the tissue distribution of ten perfluoroalkyl acids (PFAAs) detected in alewife (Alosa pseudoharengus), deepwater sculpin (Myoxocephalus thompsonii), and lake trout (Salvelinus namaycush) of the Lake Ontario aquatic piscivorous food web. To identify interspecies differences in PFAS-binding serum proteins, fish sera were pre-equilibrated with PFOS, fractionated by serial molecular weight cut-off filter fractionation, followed by liquid chromatography–tandem mass spectrometry analysis of the tryptic protein digests and the PFOS extracts of each fraction. This workflow identified similar serum proteins for all fish species. However, serum albumin was only identified in lake trout, suggesting apolipoproteins are likely the primary PFAA transporters in alewife and deepwater sculpin sera. PFAA tissue distribution analysis provided supporting evidence for interspecies variations in lipid transport and storage, which may also contribute to the varied PFAA accumulation in these species.
2023-03-11 | PXD039145 | Pride
Project description:Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of concern due to their persistence and potential adverse health effects. Epidemiological studies have linked PFAS with an increased risk of uterine diseases including fibroids however, the mechanisms involved remain to be elucidated. This study investigated the effects of individual PFAS, including long-chain “legacy” PFAS [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)] and short-chain “alternative” PFAS compounds [undecafluoro-2-methyl-3-oxahexanoic acid (GENX/HFPO-DA), perfluorobutanesulfonic acid (PFBS)], as well as a mixture of these chemicals on the function and transcriptome of an immortalized human myometrial cell line (UT-TERT). UT-TERT cells exposed to individual PFAS displayed increased cell viability and proliferation. Flow cytometry analysis revealed that PFOS and the PFAS mixture altered cell cycle progression. Migration assays demonstrated that PFOS and the PFAS mixture significantly enhanced UT-TERT cell migration. Gap junction intercellular communication (GJIC) was impaired following PFOA, PFBS, and PFAS mixture exposure, indicating potential disruptions in cell-to-cell communication within the uterine environment. Transcriptomic analysis using RNA-seq identified substantial changes in gene expression after exposure to environmentally relevant levels of individual PFAS and PFAS mixture. Pathway analysis revealed common molecular pathways associated with PFAS exposure, including Cell-to-Cell Signaling, Lipid Metabolism, and Cell Death and Survival, while other pathways were unique to specific PFAS. These findings highlight the multifaceted effects of PFAS on myometrial cells, providing insights into the potential mechanisms underlying PFAS-associated health risks. Further research is necessary to elucidate the long-term implications of PFAS exposure on uterine function and overall reproductive health.
2024-10-18 | GSE279836 | GEO
Project description: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 changes of enterohepatic circulation may play a critical role in cardiovascular risk. Objectives: Using a mouse model with high LDL-VLDL cholesterol and aortic lesion development similar to humans, the current study investigates 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, PFNA, PFHxS, GenX), each at a concentration of 2 mg/L, for 7 weeks. 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 weeks of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1.5 µg/mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1.7 µg/mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. PFAS exposure led to elevated circulating cholesterol levels after 7 weeks compared to vehicle mice, with females increasing 18% and males increasing 24%. Total circulating bile acid levels were elevated in PFAS-exposed mice by 230% in males and 290% in females compared to vehicle. PFAS decreased fecal bile acid levels by 62% in females and 59% in males. In the ileum, expression levels of the bile acid reuptake transporter ASBT were increased due to PFAS exposure. Discussion: Mice exposed to a PFAS mixture display increased circulating cholesterol and bile acids perhaps due to changes in enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk due to PFAS.
2024-08-14 | GSE263158 | GEO
Project description:Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization. Traditional toxicity testing has been unable to keep pace with the introduction of new chemicals into commerce. Consequently, there are limited or no toxicity data upon which to base a risk assessment for many chemicals to which fish and wildlife may be exposed. Per- and polyfluoroalkyl substances (PFAS) are emblematic of this issue in that most the ecological hazards of most PFAS remain uncharacterized. The present study employed a high throughput assay to identify the concentration at which 20 PFAS, with diverse properties, elicited a concerted gene expression response in larval fathead minnows (Pimephales promelas, 5-6 days post-fertilization) exposed for 24 h. Based on a reduced transcriptome approach that measured whole body expression of 1832 genes, the median transcriptomic point of departure (tPOD) for the 20 PFAS tested was 10 µM. Longer chain carboxylic acids (12-13 C-F) and an eight C-F di-alcohol, N-alkyl sulfonamide, and telomer sulfonic acid were among the most potent PFAS, eliciting gene expression responses at concentrations below 1 µM. With a few exceptions, larval fathead minnow tPODs were concordant with those based on whole transcriptome response in human cell lines. However, larval fathead minnow tPODs were often greater than those for Daphnia magna exposed to the same PFAS. The tPODs overlapped concentrations at which other sub-lethal effects have been reported in fish (available for 10 PFAS; including a range of species, life stages, and study designs). Nonetheless, fathead minnow tPODs were all orders of magnitude higher than aqueous PFAS concentrations detected in tributaries of the North American Great Lakes suggesting a substantial margin of safety in those systems, even for PFAS with significant potential for bioaccumulation. Overall, results broadly support the use of a fathead minnow larval transcriptomics assay to derive screening level potency estimates for use in ecological risk-based prioritization.
2024-10-23 | GSE246120 | GEO
Project description:The prevalence of per- and poly fluoroalkyl substances (PFASs) in the environment has prompted restrictions on legacy PFASs due to their recognized toxic effects. Consequently, alternative “replacement” PFASs have been introduced and are prevalent in environmental matrices. Few studies have investigated the molecular effects of both legacy and replacement PFASs under short-term exposures. This study aimed to address this by utilizing transcriptomic sequencing to compare the molecular impacts of exposure to concentrations 0.001–5 mg/L of the legacy PFOS and two of its replacements, PFECHS and FBSA. Using zebrafish embryos, the research assessed apical effects (mortality, morphology, and growth), identified differentially expressed genes (DEGs) and enriched pathways, and determined transcriptomic points of departure (tPoDs) for each compound. Results indicated that PFOS exhibited the highest relative potency, followed by PFECHS and then FBSA. While similarities were observed among the ranked DEGs across all compounds, over-representation analysis revealed slight differences. Notably, PFOS demonstrated the lowest tPoD identified to date. These findings raise concerns regarding the safety of emerging replacement PFASs and challenge assumptions about PFAS toxicity solely resulting from their accumulative potential. As replacement PFASs proliferate in the environment, this study underscores the need for heightened scrutiny of their effects and questions current regulatory thresholds.
2024-06-30 | GSE263667 | GEO
Project description:The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recent human and environmental health concern. There is a persistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is a relatively strong evidence linking PFAS and testicular germ cell tumors (TGCTs). However, there have been no mechanistic studies to date cancerning PFAS and TGCTs. In this report, the effects of the legacy PFAS, perfluorooctanesulfonic acid (PFOS) and the newer "clean energy" PFAS, lithium bis(trifluoromethylsulfonyl)imide (LiTFSi and called HQ-115) on TGCT tumorigenicity, survival, metabolism, and gene regulation were investigated. In vitro, proliferation and survival of both chemo-sensitive and -resistant TGCT cells were minimally affected by a wide concentration range of PFOS and HQ-115. However, both chemicals promoted the growth of TGCT cells in mouse xenografts at doses consistenet with human exposure but had minimal acute toxicity, as assessed by total body, kidney, and testis weight. PFOS, but not HQ-115, increased liver weight. Transcriptiomic alterations of PFOS-exposed normal mouse testes were dominated by cancer-related pathways and gene expression altersations associated with the H3K27me3 polycomb pathway and DNA methylation, epigenetic pathways were previously shown to be critical for the survival of TGCT cells after cisplatin-based chemotherapy. Similar pattersn of PFOS-mediated gene expression occured in PFOS-exposed cells in vitro. Metabolomic studies revealed that PFOS also altered metabolites associiated with steroid biosynthesis and fatty acid metabolism in TGCT cells, consistent with the proposed ability of PFAS to mimic fatty acied based ligands controlling lipid metabolism and the proposed role of PFAS as endocrine disrupters. Our data, this first cell and animal based study on PFAS in TGCTs, support a pro-tumorigenic effect of PFAS on TGCT biology and suggests epigenetic, metabolic, and endocrine disruption as potential mechanisms of action that are consistent with the non-mutagenic nature of the PFAS class.
2024-05-01 | GSE262137 | GEO
Project description:Despite the phase out of legacy per- and polyfluoroalkyl substances (PFAS), fluorotelomer polymers (FTP) have been used for many applications, notably textile surface coatings. FTPs are of health concerns due to their breakdown into legacy PFAS and the co-occurrence of fluorotelomer acrylate (FTAC) monomers, of which the latter may potentially react with cellular thiols. To investigate these reactions, we employed fluorous-solid phase extraction (FSPE), to enrich peptides covalently modified by 8:2 fluorotelomer acrylate (8:2 FTAC), and coupled it to a modified nano-liquid chromatography method for the identification of in vitro protein adducts using shotgun proteomics. Using this method, over one-hundred unique peptides were detected with 8:2 FTAC modifications, although none of the modified cysteine residues were annotated active site nucleophiles. In parallel, a synthetic C6F13-iodoacetamide (F13-IAM) chemical probe was used to gauge the upper-bound of PFAS-thiol reactivity. Over seven hundred peptides were detected with modifications but only 9 of 28 annotated active site cysteines in this dataset were modified by F13-IAM. Further exploration of the impacts of 8:2 FTAC adducts on protein function revealed that 8:2 FTAC modification promotes protein aggregation in vitro. These results suggest that PFAS may exhibit significant off-target reactivate and suggests a more general mechanisms of toxicity of PFAS induced protein aggregation.
2023-03-29 | MSV000091587 | MassIVE