Serum Perfluoroalkyl Substances Research Articles

TLR4 as a Potential Target of Me-PFOSA-AcOH Leading to Cardiovascular Diseases: Evidence from NHANES 2013-2018 and Molecular Docking.

Concerns have been raised regarding the effects of perfluoroalkyl substance (PFAS) exposure on cardiovascular diseases (CVD), but clear evidence linking PFAS exposure to CVD is lacking, and the mechanism remains unclear. To study the association between PFASs and CVD in U.S. population, and to reveal the mechanism of PFASs' effects on CVD. To assess the relationships between individual blood serum PFAS levels and the risk of total CVD or its subtypes, multivariable logistic regression analysis and partial least squares discriminant analysis (PLS-DA) were conducted on all participants or subgroups among 3391 adults from the National Health and Nutrition Examination Survey (NHANES). The SuperPred and GeneCards databases were utilized to identify potential targets related to PFAS and CVD, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of intersection genes were performed using Metascape. Protein interaction networks were generated, and core targets were identified with STRING. Molecular docking was achieved using Autodock Vina 1.1.2. There was a positive association between Me-PFOSA-AcOH and CVD (OR = 1.28, p = 0.022), especially coronary heart disease (CHD) (OR = 1.47, p = 0.007) and heart attack (OR = 1.58, p < 0.001) after adjusting for all potential covariates. Me-PFOSA-AcOH contributed the most to distinguishing between individuals in terms of CVD and non-CVD. Significant moderating effects for Me-PFOSA-AcOH were observed in the subgroup analysis stratified by sex, ethnicity, education level, PIR, BMI, smoking status, physical activity, and hypertension (p < 0.05). The potential intersection targets were mainly enriched in CVD-related pathways, including the inflammatory response, neuroactive ligand-receptor interaction, MAPK signaling pathway, and arachidonic acid metabolism. TLR4 was identified as the core target for the effects of Me-PFOSA-AcOH on CVD. Molecular docking results revealed that the binding energy of Me-PFOSA-AcOH to the TLR4-MD-2 complex was -7.2 kcal/mol, suggesting that Me-PFOSA-AcOH binds well to the TLR4-MD-2 complex. Me-PFOSA-AcOH exposure was significantly associated with CVD. Network toxicology and molecular docking uncovered novel molecular targets, such as TLR4, and identified the inflammatory and metabolic mechanisms underlying Me-PFOSA-AcOH-induced CVD.

A randomized controlled trial of a housing intervention to reduce endocrine disrupting chemical exposures in children

Few studies have considered household interventions for reducing endocrine disrupting chemical (EDC) exposures. We conducted a secondary analysis of a randomized controlled trial, originally designed to reduce lead exposure, to evaluate if the intervention lowered EDC exposures in young children. Study participants were children from the Cincinnati, Ohio area (n = 250, HOME Study). Prenatally, families received a housing intervention that included paint stabilization and dust mitigation, or as a control, injury prevention measures. At 24-months, we measured organophosphate esters (OPEs) and phthalates or their metabolites in dust and urine. We measured perfluoroalkyl substances (PFAS) in dust and serum at 24- and 36-months, respectively. We assessed associations between dust and biomarker EDCs using Spearman correlations, characterized EDC mixtures via principal components analysis, and investigated treatment effects using linear regression. To mitigate selection bias, we fit statistical models using inverse probability of retention weights. Correlations between dust EDCs and analogous biomarkers were weak-to-moderate (ρ’s ≤ 0.3). The intervention was associated with 23 % (95 % CI: −38, −3) lower urinary DEHP metabolites and, in a per-protocol analysis, 34 % lower (95 % CI: −55, −2) urinary MBZP. Additionally, among Black or African American children, the intervention was associated with lower serum concentrations of several PFAS (e.g., −42 %; 95 % CI: −63, −8 for PFNA). Household interventions that include paint stabilization and dust mitigation may reduce childhood exposures to some phthalates and PFAS in Blacks/African Americans. These findings highlight the need for larger studies with tailored and sustained housing interventions.

Perfluoroalkyl substances and metabolic syndrome: A cross-sectional study using data from the US national health and nutrition examination survey

BackgroundEpidemiological studies linking metabolic syndrome (MetS) and exposure to perfluoroalkyl substances (PFASs) are limited, and the observations gleaned thus far are inconclusive. The study was performed to explore the association of serum PFASs both singly and in a mixed manner with MetS, and meanwhile to examine whether this association was mediated by serum albumin in a US national population. MethodsTotal 8108 participants from the National Health and Nutrition Examination Survey, 2007–2018 were included. Four PFASs - including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoromethylheptane sulfonic acid (PFOS), and perfluorooctanoic acid (PFOA), were selected. Weighted quantile sum regression was used to evaluate mixed PFAS exposure and MetS. Multivariable logistic regression models were used to calculate odd ratio (OR) and 95 % confidence interval (95 % CI). Mediating analyses were used to evaluate the mediating effects of albumin. ResultsComparing the highest with lowest quartile yielded a multivariable-adjusted OR (95 % CI) of 1.40 (1.14–1.72) for PFHxS, 1.36 (1.09–1.70) for PFNA, 1.26 (1.00–1.58) for PFOA, and 1.50 (1.19–1.88) for PFOS when associating MetS. Per unit increment in ln-transformed PFHxS, PFNA, PFOA, and PFOS concentrations was significantly associated with 16 %, 17 %, 13 %, and 15 % increased risk of MetS, respectively. When stratified by sex, the significant association between four PFASs and MetS was only noted in females. Mixed PFAS exposure was inversely associated with MetS, and 8.1 % of this association was mediated by serum albumin (P < 0.001). ConclusionsOur findings indicate a significant and independent association of serum PFASs with MetS, and importantly this association was dose-dependent, sex-specific, and possibly mediated by serum albumin.

Perinatal Exposure to Phenols and Poly- and Perfluoroalkyl Substances and Gut Microbiota in One-Year-Old Children.

The role of the gut microbiota in human health calls for a better understanding of its determinants. In particular, the possible effects of chemicals with widespread exposure other than pharmaceuticals are little known. Our aim was to characterize the sensitivity of the early-life gut microbiota to specific chemicals with possible antimicrobial action. Within the SEPAGES French couple-child cohort, we assessed 12 phenols in repeated urine samples from 356 pregnant women and their offspring and 19 poly- and perfluoroalkyl substances (PFASs) in serum from the pregnant women. We collected stool samples from the children at one year of age, in which the V3-V4 region of the 16S rRNA gene was sequenced, allowing for gut bacterial profiling. Associations of each chemical with α- and β-diversity indices of the gut microbiota and with the relative abundance of the most abundant taxa were assessed using single-pollutant and mixture (BKMR) models. Perinatal exposure to certain parabens was associated with gut microbiota α- and β-diversity and with Firmicutes and Proteobacteria. Suggestive associations of certain phenols with genera of the Lachnospiraceae and Enterobacteriaceae families were observed, but these were not maintained after correction for multiple testing. Parabens, which have known antimicrobial properties, might disrupt the child gut microbiota, but larger studies are required to confirm these findings.

Moderate-intensity physical activity reduces the role of serum PFAS on COPD: A cross-sectional analysis with NHANES data.

Chronic obstructive pulmonary disease (COPD) has emerged as a leading cause of chronic disease morbidity and mortality globally, posing a substantial public health challenge. Perfluoroalkyl substances (PFAS) are synthetic chemicals known for their high stability and durability. Research has examined their potential link to decreased lung function. Physical activity (PA) has been identified as one of the primary modalities of the non-pharmacological treatment of COPD. To investigate the relationship between PFAS and COPD, and whether physical activity could reduce the risk of COPD caused by PFAS exposure, we used data from the NHANES 2013-2018, a cross-sectional study. Logistic regression analysis was used to examine the associations between PFAS and COPD in adult populations, and their associations in different PA types. We finally included 4857 participants in the analysis, and found that Sm-PFOS (OR: 1.250), PFOA (OR: 1.398) and n-PFOA (OR: 1.354) were closely related to COPD; After stratified by gender, age and smoking, the results showed that Sm-PFOA (OR: 1.312) was related to COPD in female adult, and PFOA (OR: 1.398) and n-PFOA (OR: 1.354) were associated with COPD in male adults; The associations of Sm-PFOS (OR: 1.280), PFOA (OR: 1.481) and n-PFOA (OR: 1.424)with COPD tended to be stronger and more consistent in over 50 years old adults; Sm-PFOS was related to COPD in current smoker (OR: 1.408), and PFOA was related to COPD in former smoker (OR: 1.487); Besides, in moderate-intensity PA group, there were no associations of Sm-PFOS, PFOA and n-PFOA with COPD stratified by gender, age and smoking. PFAS exposure may increase the risk of developing COPD, but regular moderate-intensity physical activity can protect individuals from evolving to the disease. However, longitudinal studies are needed to support these preliminary findings.

Associations of perfluoroalkyl substances with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2017-2018.

This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis. Our sample included 696 participants (≥ 18years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration. A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis. The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis.

A green analytical method for the simultaneous determination of 17 perfluoroalkyl substances (PFAS) in human serum and semen by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)

The ubiquity of perfluoroalkyl substances has raised concerns about the unintended consequences of PFAS exposure on human health. In the present study, an eco-friendly ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of 17 PFAS in human serum and semen samples. QuEChERS salts MgSO4:NaCl 4:1 (w/w) were used for the extraction. The separation of analytes was performed on an ACQUITY BEH C18 column (100 × 2.1 mm, 1.7 μm), using water:methanol 95:5 and methanol as mobile phases A and B, respectively, both containing 2 mM ammonium acetate. Multiple reaction monitoring (MRM) in negative ion mode was used, selecting two transitions for each analyte, except for perfluorobutanoic acid (PFBA) and perfluoropentanoic acid (PFPeA). The analytical method was validated according to the Organization of Scientific Area Committees (OSAC) for Forensic Sciences guidelines and AGREE approach software was used to evaluate the greenness of the method. The developed procedure was applied to the analysis of 10 paired human serum and semen samples, proving the suitability in high throughput laboratories due to the easy preparation and the reduced volume of toxic solvents. Moreover, it allows to perform further investigation on the correlation between serum and semen PFAS concentration, focusing on male reproductive system correlated pathologies, such as male infertility.

Fluorine-functionalized magnetic amino microporous organic network for enrichment of perfluoroalkyl substances

Perfluoroalkyl substances (PFAS) are persistent organic pollutants that pose significant risks to human health and the environment. Efficient and selective enrichment of these compounds was crucial for their accurate detection and quantification in complex matrices. Herein, we report a novel magnetic solid-phase extraction (MSPE) method using fluorine-functionalized magnetic amino-microporous organic network (Fe3O4@MONNH2@F7) adsorbent for the efficient enrichment of PFAS from aqueous samples. The core-shell Fe3O4@MONNH2@F7 nanosphere was synthesized, featuring magnetic Fe3O4 nanoparticles as the core and a porous amino-functionalized MONs coating as the shell, which was further modified by fluorination. The synthesized adsorbent material exhibited high specific surface area, hydrophobicity, and abundant fluorine groups, facilitating efficient and selective adsorption of PFAS via electrostatic attraction, hydrophobic-hydrophobic interactions, fluorine-fluorine interactions, π-CF interactions and hydrogen bonding. Furthermore, the MSPE method coupled with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) allowed for the rapid, sensitive, and accurate determination of ultra-trace PFAS in real water samples, human serum, and human follicular fluid. Under optimal conditions, the established MSPE method demonstrated a linear range (2 to 2000 ng L−1), with a correlation coefficient exceeding 0.9977, low limits of detection ranging from 0.54 to 1.47 ng L−1, with a relative standard deviation (RSD) < 9.1%. Additionally, the method showed excellent performance in complex real samples (recovery ratio of 81.7 to 121.6 %). The adsorption mechanism was investigated through kinetic, isotherm, and molecular simulation studies, revealing that the introduction of fluorine groups enhanced the hydrophobic interaction and fluorine-fluorine attraction between the adsorbent and PFAS. This work provides a proof-of-concept strategy for designing adsorbent materials with high efficiency and selectivity by post-modification, which has great potential for the detection and analysis of PFAS in complex samples.

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-() and beta-subunits (), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. Perfluorohexane sulfonic acid (PFHxS) [: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: ; 95% CI: , ) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with and positively with . Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with only in Black participants (; 95% CI: , ) and in participants with high school education or less (; 95% CI: , ); conversely, perfluorononanoic acid (PFNA) was negatively associated with only in White participants (; 95% CI: , ) and with only in participants with a college education or greater (; 95% CI: , ). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was . Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with , and PFNA with h-hCG. Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with and differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

Determination of seven perfluoroalkyl and polyfluoroalkyl substances in serum of pregnant women and evaluation of neonatal neurobehavior based on high performance liquid chromatography-tandem mass spectrometry

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively used as synthetic fluorine-containing compounds in various consumer products, including surfactants, cookware, lubricants, clothing, and food packaging, since the 1950s. Evidence has shown that PFASs cross the placental barrier and interfere with fetal thyroid hormone homeostasis, which is crucial for fetal growth and neurobehavioral development in children aged 2-9 years. However, no epidemiological data on the association between prenatal PFAS exposure and neonatal neurobehavioral development are available. In this study, we explored the association between prenatal PFAS exposure and neonatal neurobehavioral development based on the Ezhou cohort study. Blood samples (10 mL) were collected during the third trimester of pregnancy (28-36 weeks) at the Ezhou maternal and child health hospital. The blood specimens were centrifuged at 4000 r/min for 15 min immediately after collection, separated, stored at -80 ℃. The samples were analyzed for seven PFASs, namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonamide (PFOSA). The PFASs were separated using a C18 column (100 mm×2.1 mm, 1.7 μm) at an oven temperature of 40 ℃, injection volume of 10 μL, and flow rate of 0.4 mL/min via gradient elution with methanol and ammonium acetate aqueous solution. The instrument was operated in negative electrospray ionization mode with multiple reaction monitoring. The correlation coefficients (r2), limits of detection (LODs) and quantification (LOQs), and spiked recoveries of the seven PFASs were 0.993-0.999, 0.006-0.020 ng/mL, 0.020-0.066 ng/mL, and 84.6%-116.8%, respectively. Neonatal behavioral neurological assessment (NBNA) was used to evaluate newborn cognitive development 72 h after birth; this tool consisted of five clusters, including behavior (six items), passive muscle tone (four items), active muscle tone (four items), primitive reflexes (three items), and general assessment (three items). Each item was rated on a three-point scale (0, 1, or 2), with the 20 items having a maximum score of 40. A total of 379 mother-newborn pairs were included in the analysis. The PFASs with the highest exposure levels was PFOA, with median levels of 19.4 ng/mL. Linear regression models were used to test the effects of ln-converted PFAS levels in newborns. After adjusting for confounding factors, the linear regression model showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(β(95% CI): 0.36(-0.64, 0.08)) and general assessment(β(95% CI): 0.34(-0.61, 0.07)) in all newborns. Furthermore, PFNA exposure was associated with decreased passive muscle tone(β(95% CI): 0.38(-0.74, 0.01)) and total NBNA(β(95% CI): 0.37(-0.68, 0.06)). PFDA exposure was associated with decreased behavior(β(95% CI): 0.28(-0.54, 0.01)), while PFHxS exposure was associated with elevated total NBNA(β(95% CI): 0.27(0.05-0.48)). Gender stratification analysis showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(β(95% CI): 0.54(-0.73, 0.35)) and general assessment(β(95% CI): 0.50(-0.88, 0.13)), PFNA exposure during pregnancy was associated with decreased passive muscle tone(β(95% CI): 0.67(-1.2, 0.14)) and total NBNA(β(95% CI): 0.45(-0.91, 0.01)), PFDA exposure during pregnancy was associated with decreased behavior(β(95% CI): 0.44(-0.71, 0.17)), PFHxS exposure was associated with elevated total NBNA(β(95% CI): 0.41(0.02-0.80)) in male newborns, and PFOA exposure was associated with decreased general assessment(β(95% CI): -0.27(-0.51, 0.02)), and PFDA exposure was associated with elevated behavior(β(95% CI): 0.46(0.40-0.52)) in female newborns. The proposed method separates and detects various PFASs without the need for cumbersome pretreatment processes, and has the advantages of low LODs, satisfactory recoveries, and accurate precision. Thus, it allows for the simultaneous analysis of trace PFASs in microserum samples from pregnant women. Our results also showed that prenatal PFAS exposure can lead to neurobehavioral disorders in offspring, with male newborns showing greater sensitivity than female newborns.

Association between serum perfluoroalkyl substances concentrations and non-alcoholic fatty liver disease among Korean adults: a cross-sectional study using the National Environmental Health Survey cycle 4.

Perfluoroalkyl substances (PFAS) are widely used in industry and daily life due to their useful properties. They have a long half-life, accumulate in the body, and there is evidence that they are associated with biomarkers of lipid metabolism and liver damage. This may suggest non-alcoholic fatty liver disease (NAFLD) caused by PFAS. However, since there has been no study analyzing the relationship between PFAS and NAFLD in the entire population in Korea. We sought to confirm the relationship between serum PFAS concentration and NAFLD prevalence in Korean adults using the Korean National Environmental Health Survey (KoNEHS) cycle 4. The study was conducted on 2,529 subjects in 2018-2019 among KoNEHS participants. For the diagnosis of NAFLD, the hepatic steatosis index (HSI) was used, and the geometric mean and concentration distribution of serum PFAS were presented. Logistic regression was performed to confirm the increase in the risk of NAFLD due to changes in PFAS concentration, and the odds ratio and 95% confidence interval (CI) were calculated. In both adjusted and unadjusted models, an increased odds ratio was observed with increasing serum concentrations of total PFAS and perfluorooctane sulfonate (PFOS) in the non-obese group. In the adjusted model, the odds ratios for serum total PFAS and PFOS were 6.401 (95% CI: 1.883-21.758) and 7.018 (95% CI: 2.688-18.319). In this study, a higher risk of NAFLD based on HSI was associated with serum total PFAS, PFOS in non-obese group. Further research based on radiological or histological evidence for NAFLD diagnosis and long-term prospective studies are necessary. Accordingly, it is necessary to find ways to reduce exposure to PFAS in industry and daily life.

Relationship between crustacean consumption and serum perfluoroalkyl substances (PFAS): the Korean National Environmental Health Survey (KoNEHS) cycle 4.

Perfluoroalkyl substances (PFASs) are non-aromatic organic compounds, whose hydrogen atoms in the carbon chain substituted by fluorine atoms. PFASs exhibit developmental toxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, immunotoxicity, and hormone toxicity. PFASs are used in the production of disposable food packages, aircraft and automobile devices, cooking utensils, outdoor gear, furniture and carpets, aqueous film forming foam (AFFF), cables and wires, electronics, and semiconductors. This study aimed to determine the association between crustacean consumption and serum PFASs. Adult participants (2,993) aged ≥ 19 years were extracted from the 4th cycle data of the Korean National Environmental Health Survey (KoNEHS). Based on the 50th percentile concentrations of serum PFASs, participants were divided into the low-concentration group (LC) and the high-concentration group (HC). General characteristics, dietary factors, coated product usage, and personal care product usage, an independent t-test and χ2 test were analyzed. The odds ratio (OR) of serum PFAS concentration against crustacean consumption was estimated via logistic regression analysis adjusting for general characteristics, dietary factors, coated product usage, and personal care product usage. The OR for the HC of serum PFASs was higher in individuals with ≥once a week crustacean consumption than in those with < once a week crustacean consumption. Estimated ORs were perfluorohexanesulfonic acid 2.15 (95% confidence interval [CI]: 1.53-3.02), perfluorononanoic acid (PFNA) 1.23 (95% CI: 1.07-1.41), and perfluorodecanoic acid (PFDeA) 1.42 (95% CI: 1.17-1.74) in males, and perfluorooctanoic acid 1.48 (95% CI: 1.19-1.84), perfluorooctanesulfonic acid 1.39 (95% CI: 1.27-1.52), PFNA 1.70 (95% CI: 1.29-2.26) and PFDeA 1.43 (95% CI: 1.32-1.54) in females. This study revealed the association between the crustacean consumption and concentrations of serum PFASs in general Korean population.

Association between the dietary inflammatory index and serum perfluoroalkyl and polyfluoroalkyl substance concentrations: evidence from NANHES 2007-2018.

Diet is an important source of perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure, and the dietary inflammatory index (DII) is a tool used to assess the inflammatory potential of an individual's diet. However, limited research has explored the association between the DII and PFAS exposure in humans. This study is the first to analyze the association between the five PFASs and DII using the National Health and Nutrition Examination Survey (NHANES) 2007-2018 database. Additionally, we assessed the interaction between the DII and PFASs regarding oxidative stress and inflammatory markers, including alkaline phosphatase, albumin, neutrophil count, lymphocyte count, total bilirubin, and serum iron based on a previous study. A series of covariates were included in the analysis to reduce the confounding bias. The study included 7773 and 5933 participants based on the different models. The DII was significantly associated with serum perfluorooctanoic acid, perfluorononanoic acid, perfluorooctane sulfonic acid, and sum-PFAS. Some of the food parameters used to calculate the DII also showed associations with special PFAS serum concentrations. Specifically, dietary fiber, n-3 polyunsaturated fatty acids, energy intake, and vitamin D were associated with more than three PFASs. Higher DII levels in participants were linked to a more significant association between bilirubin (the interaction P-value is not significant), alkaline phosphatase, serum iron, neutrophil counts, and some PFASs. In conclusion, this study clarified the association between the three PFASs and DII, highlighting the diverse effects of PFASs on oxidative stress and inflammatory markers across different DII levels.

Association between probiotic consumption and serum perfluoroalkyl and polyfluoroalkyl substances (PFAS): results from NHANES, 2003–2018

BackgroundPerfluoroalkyl and polyfluoroalkyl substances (PFAS) represent a category of pervasive and enduring environmental pollutants that present a risk to human health. Although growing evidence suggests that probiotics can potentially alleviate the adverse effects of PFAS, large cross-sectional studies on the relationship between probiotic consumption and PFAS remain lacking.ObjectiveThe objective of this study is to assess the association between the exposure of probiotics and serum levels of PFAS.MethodsThis analysis included individuals aged 20 and above who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018. Probiotic consumption was considered when a participant reported consuming yogurt during the two 24-h dietary recall or using a probiotic supplement in dietary supplement questionnaires over the past 30 days.ResultsThis study involved 9469 adults, out of which 1333 had been exposed to probiotics. We found negative associations between probiotic consumption and serum concentrations of perfluorooctanoic acid (PFOA) (β: − 0.19, 95% CI − 0.35 to − 0.02; P = 0.027), and perfluorooctane sulfonic acid (PFOS) (β: − 0.1.27, 95% CI − 2.23 to − 0.32; P = 0.010). The consumption of probiotic supplements alone was associated with reduced perfluorononanoic acid (PFNA) (β: − 0.19, 95% CI − 0.28 to − 0.10; P < 0.001). No statistically significant association was identified between probiotic consumption and perfluorohexane sulphonic acid (PFHxS).ConclusionIn this cross-sectional, nationally representative study, probiotic ingestion was negatively associated with several serum PFAS compounds. These findings carry substantial implications for designing interventions that target the reduction of accumulated PFAS levels in the body and mitigating the resulting adverse health effects.

The Association of Perfluoroalkyl Substance Exposure and a Serum Liver Function Marker in Korean Adults.

Perfluoroalkyl substances (PFAS), widely used throughout industry and daily life, are currently one of the environmental pollutants garnering the most attention worldwide. Recently, environmental pollutants have had a high profile as one of the main causes of chronic liver disease, such as non-alcoholic fatty liver disease. Research on PFAS is actively underway. Although Korea has a remarkably high prevalence of chronic liver disease, and it continues to increase, only a few studies have revealed the relationship between PFAS and liver disease. In addition, regulations on PFAS in Korea are delayed compared to developed countries, such as Europe and the United States, and public interest is insufficient compared to others. Therefore, we would like to investigate the exposure of Koreans to PFAS in the blood and examine the relationship between these substances and markers of liver function (AST, ALT, and GGT). This study was based on the results of the Korean National Environmental Health Survey (KoNEHS) 2015-2017 (Cycle 3), and a total of 2961 subjects were selected. The concentration of PFAS in the blood of Korean adults was measured to be significantly higher based on the geometric mean compared to the results of recently investigated American adults based on the National Health and Nutrition Examination Survey (NHANES, 2017-2018). A multivariable linear regression analysis adjusted for age, sex, body mass index (BMI), smoking status, alcohol intake, and regular exercise was performed to examine changes in three liver function markers as the serum PFAS concentration increased. We found that some of the five PFAS (PFOA, PFOS, PFHxS, PFNA, and PFDeA) were significantly associated with increased liver enzymes. It is necessary to recognize the threat of PFAS to the human body and to discuss regulations and alternatives in earnest. Continuous follow-up studies are required through a well-designed cohort.

Higher serum concentrations of PFAS among pesticide exposed female greenhouse workers

BackgroundLong-chained poly- and perfluoroalkyl substances (PFAS) have been used in pesticide formulations but their potential impact on human PFAS exposure has not been addressed. ObjectivesTo investigate if occupationally pesticide exposed female greenhouse workers in Denmark had higher serum concentrations of PFAS than a comparable background population. MethodsSerum samples collected between 1996 and 2001 from 181 pregnant greenhouse workers and a contemporary urban population of 48 pregnant women were analyzed for eight PFAS: perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorooctane sulfonamide (FOSA), N-methyl perfluorooctane sulfonamido acetic acid (N-MeFOSAA), and N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA). ResultsThe concentrations of PFOA, PFOS, and the PFOS precursors N-MeFOSAA, N-EtFOSAA, and FOSA were higher, and PFHxS was lower, among greenhouse workers than the comparison population. After adjusting for age and parity, serum concentrations of N-MeFOSAA, N-EtFOSAA, and FOSA were 2-to-3-fold higher, and the major PFAS in serum, PFOS and PFOA, were 30–50 % higher among the greenhouse workers. ConclusionHigher serum concentrations of some legacy PFAS among female greenhouse workers indicate that exposure to pesticides is a potential pathway of exposure. Although PFAS use in pesticide applications may appear to be a minor source of exposure for the general population, this pathway deserves attention in risk assessment.

Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. ObjectivesWe aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. MethodsOne hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0–F1 fibrosis), 33 with fibrotic NASH (NASH and F2–F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at −80 °C. ResultsThe median age was 60 years, 61 % of patients were male, 46 % had diabetes and the median body mass index (BMI) was 32 kg/m2. Long-chain PFAS were associated with steatosis grade (p = 0.03). Among the nine PFAS detected in > 50 % of the patients, Perfluoro-n-heptanoic acid (PFHpA) showed significantly higher concentrations in grade 3 steatosis versus grade 1 (p = 0.02). Perfluoro-n-dodecanoic acid (PFDoA) concentrations were higher in patients with significant fibrosis (p = 0.04) and PFHpA in patients with advanced fibrosis (p = 0.02). The association between PFHpA and steatosis grade remained significant in multivariate analysis adjusted for age, gender, BMI, diabetes presence and dyslipidemia (p = 0.004). DiscussionOur study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through β-oxidation and biosynthesis of fatty acids.

Serum perfluoroalkyl substances and growth and development in US adolescents: a nationally representative cross-sectional study.

Our findings indicate a negative association between serum PFAS levels and weight, and BMI among adolescents, and we observed that the negative association was sex-specific in weight. • Wide exposure to PFAS has led to concerns about its adverse effects, especially for children during their growth and development. • So far, much research has evaluated the effects of prenatal PFAS exposures on children, and the current results are mixed, with some research showing that there are sex differences. • This study investigated the relationship between serum PFAS levels and height and weight in adolescents and is a good addition to current research. • Our study found that exposure to PFAS negatively affects adolescent growth and development and that this effect is sex-specific.

Perfluoroalkyl substances (PFAS) and lead (Pb) as “cardiovascular disruptors” in 9–11-year-old children living in Syracuse, New York, United States

ObjectivePer- and polyfluoro–alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). MethodsWe assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9–11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). ResultsSignificant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater “vascular reactivity” (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (β = 0.21, p = 0.010). ConclusionTo our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as “cardiovascular disruptors” in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.

Decreased levels of perfluoroalkyl substances in patients receiving hemodialysis treatment

Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS.