Perfluorooctane Sulfonate Levels Research Articles

Perfluorooctane Sulfonate (PFOS) Negatively Impacts Prey Capture Capabilities in Larval Zebrafish.

Per- and polyfluoroalkyl substances (PFAS) are widely used in many industrial and domestic applications, which has resulted in unintentional human exposures and bioaccumulation in blood and other organs. Perfluorooctane sulfonate (PFOS) is among the most prevalent PFAS in the environment and has been postulated to affect brain functions in exposed organisms. However, the impacts of PFOS in early neural development have not been well described. We used zebrafish larvae to assess the effects of PFOS on two fundamental complex behaviors, prey capture and learning. Zebrafish exposed to PFOS concentrations ranging from 2 to 20 µM for differing 48-h periods were viable through early larval stages. In addition, PFOS uptake was unaffected by the presence of a chorion. We employed two different experimental paradigms; first we assessed the impacts of increasing organismal PFOS bioaccumulation on prey capture and learning, and second, we probed stage-specific sensitivity to PFOS by exposing zebrafish at different developmental stages (0-2 vs. 3-5 days post fertilization). Following both assays we measured the amount of PFOS present in each larva and found that PFOS levels varied in larvae from different groups within each experimental paradigm. Significant negative correlations were observed between larval PFOS accumulation and percentage of captured prey, whereas nonsignificant negative correlations were observed between PFOS accumulation and experienced-induced prey capture learning. These findings suggest that PFOS accumulation negatively affects larval zebrafish's ability to perform complicated multisensory behaviors and highlights the potential risks of PFOS exposure to animals in the wild, with implications for human health. Environ Toxicol Chem 2024;43:847-855. © 2023 SETAC.

Evaluation of fatty acids and carnitine as biomarkers of PFOS exposure in biota (fish and dolphin) from Galveston Bay and the northwestern Gulf of Mexico

Perfluorooctane sulfonate (PFOS) is a ubiquitous pollutant that elicits a wide range of toxic effects in exposed biota. Coastal zones in highly urbanized or industrial areas are particularly vulnerable to PFOS pollution. At present, information is lacking on biomarkers to assess PFOS effects on aquatic wildlife. This study investigated the efficacy of l-carnitine (or carnitine) and fatty acids as biomarkers of PFOS exposure in aquatic biota. The levels of PFOS, total and free carnitine, and 24 fatty acids (measured as fatty acid methyl esters or FAMEs) were measured in the liver, and muscle or blubber, of fish and dolphins sampled from Galveston Bay and the northern Gulf of Mexico (nGoM). Overall, bottlenose dolphins (Tursiops truncatus) had the highest hepatic PFOS levels. Galveston Bay fish, gafftopsail catfish (Bagre marinus), red drum (Sciaenops ocellatus), and spotted seatrout (Cynoscion nebulosus), had hepatic PFOS levels ∼8-13× higher than nGoM pelagic fish species, red snapper (Lutjanus campechanus) and yellowfin tuna (Thunnus albacares). The multivariate analysis of PFOS liver body-burdens and biomarkers found carnitine to be a more modal biomarker of PFOS exposure than FAMEs. Significant positive correlation of hepatic PFOS levels with total carnitine was evident for biota from Galveston Bay (fish only), and a significant correlation between PFOS and total and free carnitine was evident for biota from the nGoM (fish and dolphins). Given the essential role of carnitine in mediating fatty acid β-oxidation, our results suggest carnitine to be a likely candidate biomarker of environmental PFOS exposure and indicative of potential dyslipidemia effects.

SAT441 Association Of PFOS Exposure And The Risk Of Coronary Artery Disease In Postmenopausal Women

Abstract Disclosure: A. Arredondo Eve: None. E. Tunc: None. D. Mehta: None. H. Erbak-Yilmaz: None. S. Volkan Emren: None. F. Akyildiz-Akcay: None. Z. Madak Erdogan: None. Cardiovascular diseases (CVD) are the number one cause of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence cardiovascular disease risk. Perfluoroalkyl substances (PFAS) are a class of highly fluorinated chemicals used in our daily household necessities and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between Perfluorooctanoic acid (PFOA), Perfluorooctane sulfonate (PFOS), Perfluorobutanesulfonic acid (PFBS) in postmenopausal women from our previously established CVD cohort using liquid chromatography with tandem mass spectrometry (LC-MS-MS) analysis and supported by machine learning approaches. Here we show that PFOS levels were significantly higher in postmenopausal women with coronary cardiovascular disease (CAD) when compared to control and coronary microvascular disease (CMD) group. We also found that specific metabolite concentrations (alanine, isoleucine, proline, and tyrosine) were negatively associated with serum PFOS levels. A significant correlation with changes in the expression of proteins such as growth hormone (GH), tyrosine-protein kinase Mer (MERTK), metalloproteinase inhibitor 4 (TIMP4), transferrin receptor protein 1 (TFRC), thrombospondin-2 (THBS2) and PFOS was observed. Our findings may provide new insight into the potential mechanism underlying the increased risk of cardiovascular events in postmenopausal women and the emerging evidence on PFAS-induced risk of cardiovascular diseases in this vulnerable population. Presentation: Saturday, June 17, 2023

A metabolomic investigation of serum perfluorooctane sulfonate and perfluorooctanoate

BackgroundExposures to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), environmentally persistent chemicals detectable in the blood of most Americans, have been associated with several health outcomes. To offer insight into their possible biologic effects, we evaluated the metabolomic correlates of circulating PFOS and PFOA among 3,647 participants in eight nested case-control serum metabolomic profiling studies from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. MethodsMetabolomic profiling was conducted by Metabolon Inc., using ultra high-performance liquid chromatography/tandem accurate mass spectrometry. We conducted study-specific multivariable linear regression analyses estimating the associations of metabolite levels with levels of PFOS or PFOA. For metabolites measured in at least 3 of 8 nested case-control studies, random effects meta-analysis was used to summarize study-specific results (1,038 metabolites in PFOS analyses and 1,100 in PFOA analyses). ResultsThe meta-analysis identified 51 and 38 metabolites associated with PFOS and PFOA, respectively, at a Bonferroni-corrected significance level (4.8x10-5 and 4.6x10-5, respectively). For both PFOS and PFOA, the most common types of associated metabolites were lipids (sphingolipids, fatty acid metabolites) and xenobiotics (xanthine metabolites, chemicals). Positive associations were commonly observed with lipid metabolites sphingomyelin (d18:1/18:0) (P = 2.0x10-10 and 2.0x10-8, respectively), 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (P = 2.7x10-15, 1.1x10-17), and lignoceroylcarnitine (C24) (P = 2.6x10-8, 6.2x10-6). The strongest positive associations were observed for chemicals 3,5-dichloro-2,6-dihydroxybenzoic acid (P = 3.0x10-112 and 6.8x10-13, respectively) and 3-bromo-5-chloro-2,6-dihydroxybenzoic acid (P = 1.6x10-14, 2.3x10-6). Other metabolites positively associated with PFOS included D-glucose (carbohydrate), carotene diol (vitamin A metabolism), and L-alpha-aminobutyric acid (glutathione metabolism), while uric acid (purine metabolite) was positively associated with PFOA. PFOS associations were consistent even after adjusting for PFOA as a covariate, while PFOA associations were greatly attenuated with PFOS adjustment. ConclusionsIn this large metabolomic study, we observed robust positive associations with PFOS for several molecules. Further investigation of these metabolites may offer insight into PFOS-related biologic effects.

First Observations of a Potential Association Between Accumulation of Per- and Polyfluoroalkyl Substances in the Central Nervous System and Markers of Alzheimer's Disease.

The entire human population is exposed to persistent organic pollutants throughout their lives. Among them, per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in industrial and consumer products that are known to exert adverse effects on human health. As they bioaccumulate in the human brain and are known to be neurotoxic in experimental models, they are assumed to be involved in neurodegenerative processes. In this proof-of-concept study, we measured the level of 18 PFAS in cerebrospinal fluid (CSF) from 8 patients hospitalized with suspected normal pressure hydrocephalus. We then analyzed whether PFAS levels could be related to both biological and clinical markers of Alzheimer's disease. We showed that PFAS and perfluorooctanesulfonate were found in all CSF samples from a French region without fluorochemical industries. Moreover, we observed a significant difference between the levels of PFAS and perfluorooctanesulfonate in the CSF of patients with both Alzheimer's disease markers and cognitive impairment compared with those with only 1 or neither. Two previous studies have shown that PFAS levels in human CSF increase with age and are linked to impaired blood-brain barrier integrity. Our results provide the first evidence of a link between PFAS accumulation in the central nervous system and clinical and biological markers of Alzheimer's disease.

Association between per- and polyfluoroalkyl substances and risk of hypertension: a systematic review and meta-analysis.

Existing evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent. Therefore, we aimed to explore the relationship between PFASs and hypertension through this systematic review and meta-analysis. We searched PubMed, Embase, and the Web of Science databases for articles published in English that examined the relationship between PFASs and hypertension before 13 August 2022. The random effects model was used to aggregate the evaluation using Stata 15.0 for Windows. We also conducted subgroup analyses by region and hypertension definition. In addition, a sensitivity analysis was carried out to determine the robustness of the findings. The meta-analysis comprised 15 studies in total with 69,949 individuals. The risk of hypertension was substantially and positively correlated with exposure to perfluorooctane sulfonate (PFOS) (OR = 1.31, 95% CI: 1.14, 1.51), perfluorooctanoic acid (PFOA) (OR = 1.16, 95% CI: 1.07, 1.26), and perfluorohexane sulfonate (PFHxS) (OR = 1.04, 95% CI: 1.00, 1.09). However, perfluorononanoic acid (PFNA) exposure and hypertension were not significantly associated (OR = 1.08, 95% CI: 0.99, 1.17). We evaluated the link between PFASs exposure and hypertension and discovered that higher levels of PFOS, PFOA, and PFHxS were correlated with an increased risk of hypertension. However, further high-quality population-based and pathophysiological investigations are required to shed light on the possible mechanism and demonstrate causation because of the considerable variability. https://www.crd.york.ac.uk/prospero/ PROSPERO, registration number: CRD 42022358142.

Health Risk Exposure Assessment of Migration of Perfluorooctane Sulfonate and Perfluorooctanoic Acid from Paper and Cardboard in Contact with Food under Temperature Variations.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are extensively used in food-contact paper and cardboard. However, they may migrate from food-contact materials to food, and the migration rate may be increased at elevated temperatures. In addition, there is a positive association of PFOS/PFOA levels with total cholesterol. Therefore, this study aims to assess the human health risk of increased total cholesterol associated with long-term exposure to PFOS and PFOA migration from food-contact paper and cardboard under temperature variation scenarios in adults. An exposure assessment was performed using an uptake dose model to estimate the uptake doses of PFOS and PFOA for the high-, intermediate-, and low-exposure scenarios. Benchmark dose (BMD) modeling was conducted to describe the dose-response relationships between PFOS/PFOA and total cholesterol levels. Finally, a margin of exposure (MOE) approach was used to characterize the risk. The results of the exposure assessment showed that PFOS and PFOA uptake doses in the high-exposure scenarios were around one and two orders of magnitude greater than those in the intermediate- and low-exposure scenarios, respectively. Under high-exposure scenarios, the uptake levels of hundredth-percentile PFOS and PFOA at high temperatures may raise health concerns (MOE < 1). This study provides a methodology to assess the health risks associated with exposure to migration of food contaminants from various types of paper and cardboard that come into contact with food.

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Per- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs]=1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.

Perfluoroalkyl substance exposure is associated with asthma and innate immune cell count in US adolescents stratified by sex.

Exposure to perfluoroalkyl substances (PFAS) may be harmful to humans; however, previous studies have been inconsistent regarding the potential for PFAS-induced immunosuppresion. This study explored the relationship between PFAS exposure and risks of asthma, wheezing, and immunosuppression in 12-19year-olds using the National Health and Nutrition Examination Survey (NHANES) data. Logistic regression models were used to reveal associations between serum PFAS levels and risks of asthma, wheezing, asthma attack, and emergency department visits. Pearson's correlation was used to determine the relationship between serum PFAS levels and leukocyte count. Data were also stratified by sex. We found that medium-low levels of serum perfluorooctane sulfonate (PFOS) (6.90-12.40ng/mL) and serum perfluorooctanoic acid (PFOA) (2.43-3.60ng/mL) were negatively related, respectively, to current asthma and wheezing in boys, and to wheezing in girls. Meanwhile, boys with medium-high levels (1.50-3.00ng/mL) of serum perfluorohexanesulfonate (PFHxS) had a high risk of wheezing. Among asthmatic participants, both medium-high levels (3.75-5.07ng/mL) of serum PFOA and high levels (> 3.92ng/mL) of PFHxS correlated with asthma attacks in boys; likewise, medium-low levels (0.70-0.99ng/mL) of serum PFNA correlated with asthma attacks in girls. Also, PFOA and PFNA levels were weakly positively correlated with basophil count, whereas PFOS levels were weakly negatively correlated with eosinophils in asthmatic boys, indicating that basophils may be important in the immune response to PFAS exposure among asthmatics.

Emerging and legacy contaminants in common minke whale from the Barents sea

Persistent organic pollutants (POPs), including brominated flame retardants (BFRs), perfluoroalkyl substances (PFAS) and metals, can accumulate in marine mammals and be transferred to offspring. In this study, we analyzed 64 lipophilic POPs, including four emerging BFRs, in the blubber, liver and muscle of 17 adult common minke whales (Balaenoptera acutorostrata) from the Barents Sea to investigate occurrence and tissue partitioning. In addition, the placental transfer concentration ratios of 14 PFAS and 17 metals were quantified in the muscle of nine female-fetus pairs to investigate placental transfer. Legacy lipophilic POPs were the dominating compound group in every tissue, and we observed generally lower levels compared to previous studies from 1992 to 2001. We detected the emerging BFRs hexabromobenzene (HBB) and pentabromotoluene (PBT), but in low levels compared to the legacy POPs. We detected nine PFAS, and levels of perfluorooctane sulfonate (PFOS) were higher than detected from the same population in 2011, whilst levels of Hg were comparable to 2011. Levels of lipophilic contaminants were higher in blubber compared to muscle and liver on both a wet weight and lipid adjusted basis, but tissue partitioning of the emerging BFRs could not be determined due to the high number of samples below the limit of detection. The highest muscle ΣPFAS levels were quantified in fetuses (23 ± 8.7 ng/g ww), followed by adult males (7.2 ± 2.0 ng/gg ww) and adult females (4.5 ± 1.1 ng/g ww), showing substantial placental transfer from mother to fetus. In contrast, Hg levels in the fetus were lower than the mother. Levels were under thresholds for risk of health effects in the whales. This study is the first to report occurrence and placental transfer of emerging contaminants in common minke whales from the Barents Sea, contributing valuable new data on pollutant levels in Arctic wildlife.

Perfluorooctanoic Acid and Perfluorooctane Sulfonate in Human Milk: First Survey from Lebanon

Human milk is the primary source of nutrition for infants in their first year of life. Its potential contamination with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), a group of toxic man-made chemicals, is a health concern that may threatens infants' health. Our study aims to assess the levels of PFOA and PFOS in the breast milk of Lebanese lactating mothers and the maternal factors associated with their presence. High-performance liquid chromatography (HPLC) coupled with a Micromass Quattro micro API triple quadrupole mass spectrometer was used to detect the level of contamination in 57 collected human milk samples. PFOA and PFOS were present in 82.5% and 85.7% of the samples, respectively, while PFOA levels ranged between 120 and 247 pg/mL with a median of 147 pg/mL, and those of PFOS ranged between 12 and 86 pg/mL with a median of 27.5 pg/mL. The median contamination for PFOA exceeded the threshold set by the European Food Safety Authority (EFSA) (60 pg/mL); however, that of PFOS was below the threshold (73 pg/mL). The consumption of bread, pasta, meat, and chicken more than twice per week and that of white tubers and roots at least once per week was significantly associated with higher levels of PFOA (p < 0.05). No significant association was found between maternal age, BMI, parity, level of education, place of residence, source of water used, and smoking with the levels of PFOA and PFOS in the human milk. Additionally, the consumption of cereals at least twice per week was significantly associated with higher levels of PFOS. These findings call for actions to improve the local environmental and agricultural practices, and the regulations and standards for inspecting imported food. It is important to highlight that the benefits of breastfeeding outweigh the reported contamination with PFOS and PFOA in our study.

Plasma PFOA and PFOS Levels, DNA Methylation, and Blood Lipid Levels: A Pilot Study.

Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) is associated with blood lipids in adults, but the underlying mechanisms remain unclear. This pilot study aimed to investigate the associations between PFOA or PFOS and epigenome-wide DNA methylation and assess the mediating effect of DNA methylation on the PFOA/PFOS-blood lipid association. We measured plasma PFOA/PFOS and leukocyte DNA methylation in 98 patients enrolled from the hospital between October 2018 and August 2019. The median plasma PFOA/PFOS levels were 0.85 and 2.29 ng/mL. Plasma PFOA and PFOS levels were significantly associated with elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels. There were 63/87 CpG positions and 8/11 differentially methylated regions (DMRs) associated with plasma PFOA/PFOS levels, respectively. In addition, 5 CpG positions (annotated to AFF3, CREB5, NRG2, USF2, and intergenic region) and one DMR annotated to IRF6 may mediate the association between plasma PFOA/PFOS and LDL levels (mediated proportion from 7.29 to 46.77%); two CpG positions may mediate the association between plasma PFOA/PFOS and TC levels (annotated to CREB5 and USF2, mediated proportion is around 30%). The data suggest that PFOA/PFOS exposure alters DNA methylation. More importantly, the association of PFOA/PFOS with lipid indicators was partly mediated by DNA methylation changes in lipid metabolism-related genes.

Metabolomic, Lipidomic, Transcriptomic, and Metagenomic Analyses in Mice Exposed to PFOS and Fed Soluble and Insoluble Dietary Fibers.

Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant that has become a significant concern around the world. Exposure to PFOS may alter gut microbiota and liver metabolic homeostasis in mammals, thereby increasing the risk of cardiometabolic diseases. Diets high in soluble fibers can ameliorate metabolic disease risks. We aimed to test the hypothesis that soluble fibers (inulin or pectin) could modulate the adverse metabolic effects of PFOS by affecting microbe-liver metabolism and interactions. Male C57BL/6J mice were fed an isocaloric diet containing different fibers: a) inulin (soluble), b) pectin (soluble), or c) cellulose (control, insoluble). The mice were exposed to PFOS in drinking water () for 7 wk. Multi-omics was used to analyze mouse liver and cecum contents. In PFOS-exposed mice, the number of differentially expressed genes associated with atherogenesis and hepatic hyperlipidemia were lower in those that were fed soluble fiber than those fed insoluble fiber. Shotgun metagenomics showed that inulin and pectin protected against differences in microbiome community in PFOS-exposed vs. control mice. It was found that the plasma PFOS levels were lower in inulin-fed mice, and there was a trend of lower liver accumulation of PFOS in soluble fiber-fed mice compared with the control group. Soluble fiber intake ameliorated the effects of PFOS on host hepatic metabolism gene expression and cecal content microbiome structure. Results from metabolomic, lipidomic, and transcriptomic studies suggest that inulin- and pectin-fed mice were less susceptible to PFOS-induced liver metabolic disturbance, hepatic lipid accumulation, and transcriptional changes compared with control diet-fed mice. Our study advances the understanding of interaction between microbes and host under the influences of environmental pollutants and nutrients. The results provide new insights into the microbe-liver metabolic network and the protection against environmental pollutant-induced metabolic diseases by high-fiber diets. https://doi.org/10.1289/EHP11360.

Spatiotemporal and life history related trends of per- and polyfluoroalkyl substances in Indo-Pacific finless porpoises from south China sea (2007–2020)

Per- and polyfluoroalkyl substances (PFASs) levels in Indo-Pacific finless porpoises (Neophocaena phocaenoides) in the Pearl River Estuary (PRE), near the most economically developed region in China, have not been characterized. We measured the hepatic concentrations of twelve PFASs, including nine perfluoroalkyl carboxylic acids (PFCAs) and three perfluoroalkane sulfonic acids (PFSAs) in the finless porpoises (n = 21) collected from the PRE between 2007 and 2020. The average level of PFSAs was more than 2-times higher than that of PFCAs. The order of six dominant PFASs was perfluorooctane sulfonate (PFOS) > perfluoroundecanoic acid (PFUdA) > perfluorodecanoic acid (PFDA) > perfluorotridecanoic acid (PFTrDA) > perfluorononanoic acid (PFNA) > perfluorododecanoic acid (PFDoDA). The levels of Hepatic PFOS of 29% samples exceeded the no observable adverse effect level (NOAEL) values. The concentration of PFASs in males was significant higher than in females. PFASs levels were significantly negatively correlated with body length in males and positively correlated in females. PFASs levels in the PRE finless porpoises were lower than in humpback dolphins possibly due to different foraging habitat toward the coast and the consumption of less fish. PFCAs levels in finless porpoises from the western PRE were higher compared to Hong Kong, possibly due to the high-intensity sources of terrestrial anthropogenic pollutants. Significant increasing spatiotemporal trends of PFSAs, PFCAs and PFASs were found in finless porpoises from 2007 to 2020, suggesting a continuously increased risk of PFASs exposure for PRE cetaceans in the last decade.

Associations between serum perfluoroalkyl acid (PFAA) concentrations and health related biomarkers in firefighters

ObjectivesFirefighters who used aqueous film forming foam in the past have experienced elevated exposures to perfluoroalkyl acids (PFAAs). The objective of this study was to examine the associations between clinical chemistry endpoints and serum concentrations of perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS) and perfluorooctane sulfonate (PFOS) in firefighters. Multiple linear regression was used to assess relationships between PFAA serum concentrations and biochemical markers for cardiovascular disease, kidney-, liver- and thyroid function, in a cross-sectional survey of 783 firefighters with elevated levels of PFHxS, PFHpS and PFOS in relation to the most recently reported levels in the general Australian population. Linear logistic regression was used to assess the odds ratios for selected self-reported health outcomes. Repeated measures linear mixed models were further used to assess relationships between PFAAs and biomarkers for cardiovascular disease and kidney function longitudinally in a subset of the firefighters (n = 130) where serum measurements were available from two timepoints, five years apart. In the cross-sectional analysis, higher levels of all PFAAs were significantly associated with higher levels of biomarkers for cardiovascular disease (total-cholesterol, and LDL-cholesterol). For example, doubling in PFOS serum concentration were associated with increases in total cholesterol (β:0.111, 95% confidence interval (95%CI): 0.026, 0.195 mmol/L) and LDL-cholesterol (β: 0.104, 95%CI:0.03, 0.178 mmol/L). Doubling in PFOA concentration, despite not being elevated in the study population, were additionally positively associated with kidney function marker urate (e.g., β: 0.010, 95%CI; 0.004, 0.016 mmol/L) and thyroid function marker TSH (e.g., β: 0.087, 95%CI: 0.014, 0.161 mIU/L). PFAAs were not associated with any assessed self-reported health conditions. No significant relationships were observed in the longitudinal analysis. Findings support previous studies, particularly on the association between PFAAs and serum lipids.

Global DNA methylation mediates the association between serum perfluorooctane sulfonate and carotid intima-media thickness in young and middle-aged Taiwanese populations

PurposePerfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in the manufacture of many everyday products. Previous reports have shown PFAS exposure may contribute to cardiovascular diseases (CVD). Recent studies have also identified a critical role for DNA methylation, a model of epigenetic regulation, in the pathogenesis of CVD. Additionally, PFAS has been shown to affect DNA methylation. Our previous study reported the positive association between serum perfluorooctane sulfonate (PFOS) levels and mean carotid intima-media thickness (CIMT), a biomarker of arteriosclerosis, in a cohort composed of adolescent and young adult Taiwanese. However, the contribution of DNA methylation in the mechanism of PFOS-induced arteriosclerosis has never been explored in previous literature. Approach and resultsIn this cross-sectional study, we included 1425 young and middle-aged Taiwanese individuals (12–63 years) to investigate the correlation between serum PFOS levels, 5mdC/dG (a global DNA methylation marker) and the mean CIMT. We showed that the positive association between serum PFOS levels, 5mdC/dG, and mean CIMT. The regression coefficients of mean CIMT with a one-unit increase in ln-PFOS concentration were higher when the levels of 5mdC/dG were above the 50th percentile in the multiple regression analysis. In the structural equation model (SEM), the results showed that serum PFOS levels were directly correlated with mean CIMT and indirectly correlated with CIMT through 5mdC/dG. ConclusionsOur results showed that PFOS exposure has direct associations on arteriosclerosis and indirect direct associations on arteriosclerosis through DNA methylation. The results suggest that DNA methylation might regulate the relationship between PFOS and arteriosclerosis in the study subjects. Additional works are required to understand the causal inference between PFOS, DNA methylation, and arteriosclerosis.

Evaluated serum perfluoroalkyl acids and their relationships with the incidence of rheumatoid arthritis in the general population in Hangzhou, China

Perfluoroalkyl acids (PFAAs) are widely present in human blood, and have many toxic effects on humans. However, effects of PFAA exposure on the risk of rheumatic immune diseases are limited. In the present study, occurrence of 7 PFAAs, including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), perfluorododecanoate (PFDoA), and perfluorotrdecanoate (PFTrA), were measured in serum samples from 156 healthy people (controls) and 156 rheumatoid arthritis (RA) cases living in Hangzhou, China. We also investigated the relationships among cumulative PFAA levels in serum, some immune markers, and the incidence of RA. The results showed that PFOA (6.1 and 11.8 ng/mL) had the highest mean serum concentrations, followed by PFOS (3.2 and 3.4 ng/mL) and PFDA (0.86 and 2.6 ng/mL), in both controls and RA cases. Cumulative exposure to PFOA in the study population were positively correlated with the levels of rheumatoid factors (rs = 0.69, p < 0.01) and anti-cyclic citrullinated peptide antibody (rs = 0.56, p < 0.05). Moreover, significant associations of PFOA concentrations with odds ratios (OR) of RA (OR = 1.998, confidence interval (CI): 1.623, 2.361, p = 0.01) were found by adjusting for various covariates. The crude and adjusted OR for RA was respective 1.385 (95% CI: 1.270, 1.510, p = 0.04) and 1.381 (95% CI: 0.972, 1.658, p = 0.06) for a unit increase in serum PFOS levels, but the adjusted results were not significant. Overall, this case-control study found that human serum PFOA concentrations were positively correlated with RF and ACPA levels.

Associations of serum PFOA and PFOS levels with incident hypertension risk and change of blood pressure levels

Evidence on the associations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with hypertension or blood pressure (BP) levels was limited and inconsistent. The present prospective study aims to evaluate the longitudinal associations of serum levels of PFOA and PFOS with incident hypertension risk and change of blood pressure levels. At baseline 1080 participants (mean age 62 years, 58.9% females) free of hypertension, cardiovascular disease, diabetes, and cancer were followed up for nearly 5 years. Baseline serum levels of PFOA and PFOS were measured with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Hypertension was defined as any of (1) self-reported physician-diagnosed hypertension (2) use of hypotension drugs (3) measured systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Change of BP was evaluated as a difference between twice measurements (BP at follow-up visit－BP at baseline). After adjustment for multiple covariates, serum PFOS levels were negatively correlated with risk of hypertension [RR per lg-unit = 0.94 (95% CI: 0.88, 0.99)] and change of systolic BP [β = −1.48 (95% CI: −2.56, −0.41)]. The highest vs lowest quartiles of PFOS concentration was negatively associated with hypertension risk. Compared with Q1, the RRs (95% CIs) for Q2, Q3, and Q4 were 0.83 (0.67–0.98), 0.81 (0.67–0.97), and 0.81(0.67–0.97), respectively (p for trend = 0.016). The negative associations remained in females but not in males (p for interaction = 0.44). No significant association of PFOA with hypertension risk was observed. Further studies are needed to validate our findings.

Effect of Plasma and Blood Donations on Levels of Perfluoroalkyl and Polyfluoroalkyl Substances in Firefighters in Australia

Elevated levels of blood perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been associated with a range of adverse health outcomes. Firefighters have been exposed to PFASs in firefighting foams and have previously been shown to have higher PFAS levels in blood samples than the general population. No interventions have been shown to reduce PFAS levels. To examine the effect of blood or plasma donations on PFAS levels in firefighters in Australia. This 52-week, open-label, randomized clinical trial enrolled participants from May 23 to August 23, 2019. Participants were 285 Fire Rescue Victoria staff or contractors with serum levels of perfluorooctane sulfonate (PFOS) of 5 ng/mL or more who were eligible to donate blood, had not donated blood in the 3 months prior to randomization, and were able to provide written informed consent. Analysis was performed on an intention-to-treat basis from May to July 2021. Firefighters with baseline PFOS levels of 5 ng/mL or more were randomly assigned to donate plasma every 6 weeks for 12 months, donate blood every 12 weeks for 12 months, or be observed only. The primary end points were changes in the serum PFOS and perfluorohexane sulfonic acid (PFHxS) levels after 12 months of plasma or blood donations or after observation only. Secondary end points included changes in serum PFAS levels from week 52 to week 64, changes in other PFASs, and changes in complete blood count, biochemistry, thyroid function, and lipid profile from screening to week 52. A total of 285 firefighters (279 men [97.9%]; mean [SD] age, 53.0 [8.4] years) were enrolled; 95 were randomly assigned to donate plasma, 95 were randomly assigned to donate blood, and 95 were randomly assigned to be observed. The mean level of PFOS at 12 months was significantly reduced by plasma donation (-2.9 ng/mL; 95% CI, -3.6 to -2.3 ng/mL; P < .001) and blood donation (-1.1 ng/mL; 95% CI, -1.5 to -0.7 ng/mL; P < .001) but was unchanged in the observation group. The mean level of PFHxS was significantly reduced by plasma donation (-1.1 ng/mL; 95% CI, -1.6 to -0.7 ng/mL; P < .001), but no significant change was observed in the blood donation or observation groups. Analysis between groups indicated that plasma donation had a larger treatment effect than blood donation, but both were significantly more efficacious than observation in reducing PFAS levels. Plasma and blood donations caused greater reductions in serum PFAS levels than observation alone over a 12-month period. Further research is needed to evaluate the clinical implications of these findings. anzctr.org.au Identifier: ACTRN12619000204145.

Literature Review: Cancers Among Workers Exposed To Perfluorooctane Sulfonate (PFOS)

Introduction: Cancer is a disease with a high mortality rate in Indonesia. One of the chemical exposures that can cause cancer is perfluorooctanesulfonyl fluoride/perfluoro octane sulphonate (PFOS). PFOS is a chemical that is widely used due to its diverse functions, including use in fire extinguishers, waterproof materials in food boxes and furniture, and household hygiene products. Long-term exposure to workers affected by PFOS is suspected to be one of the risk factors for cancer. Methods: The author conducted a literature search of online search engines in 3 sources PubMed, Google Scholar, and JSTOR databases. The inclusion criteria in this study are articles in English, full text available, and conducted on the working population. The author has not restricted search within the last 5 years due to the limited reference of the topic. Results: Out of a total of 5 articles examined, the authors found the incidence of bladder cancer in workers as much as 1.28 times, there was even a death rate of 12.77 times in workers with PFOS exposure due to bladder cancer, although the results did not statistically significantly. Other studies have shown increased levels of PFOS in the blood but were not associated with changes in other laboratory examinations associated with health problems in workers. Conclusions: The results of the literature study found no significant association in cancer occurrence based on the length of PFOS exposure in workers. The literature search results also found no direct association between PFOS exposure to possible health problems.