Polyfluoroalkyl Substances Mixtures Research Articles

P-591 Per- and Polyfluoroalkyl Substances Serum Concentrations and Polycystic Ovary Syndrome among Women Attending a Fertility Clinic

Abstract Study question What is the association between serum per- and poly-fluoroalkyl substances (PFAS) concentrations and polycystic ovary syndrome (PCOS) risk in populations with low-level PFAS exposure. Summary answer Higher serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with elevated risk of PCOS among women attending a U.S. fertility clinic. What is known already Previous studies reported that exposure to high-levels of PFAS exposure was associated with elevated risk of PCOS. However, studies evaluating PCOS risk in populations with exposure to lower levels of PFAS are limited. Study design, size, duration A cohort study of 502 females who sought fertility evaluation for medically assisted reproduction in a U.S. fertility clinic and had similar PFAS exposure level as the general U.S. population. Participants/materials, setting, methods Nine PFAS were quantified in non-fasting serum samples collected at study entry. Diagnosis of PCOS was based on the Rotterdam criteria after study entry before treatment. We used logistic regression to examine the odds ratio (OR) of PCOS in relation to PFAS concentrations (continuous and by tertiles). We applied quantile g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) to examine the joint associations of PFAS mixture with PCOS. Main results and the role of chance A total of 38 (7.6%) females were diagnosed with PCOS. Doubling of serum PFOS and PFHxS concentrations were associated with higher odds of PCOS [OR (95%CI): 1.70 (1.06, 2.81) and 1.45 (1.02, 2.08), respectively]. There was a dose-response relationship of PFOS with PCOS risk (p of trend by tertiles = 0.07). Both QGC and BKMR identified PFOS as the most important contributor among the PFAS mixture to PCOS risk. No clear joint effect was found for other examined PFAS nor for PFAS as a total mixture on PCOS risk. Limitations, reasons for caution Findings in this subfertile population may not be directly generalizable to reproductive aged women in the general population. Wider implications of the findings Our findings are consistent with existing evidence from populations with higher concentrations of some of the evaluated PFAS and supports the potential adverse effects of PFAS on female reproductive function. Larger prospective studies are needed to validate the findings. Trial registration number NA

Evaluation of separation by high shear mixing for per- and poly-fluoroalkyl substances (PFAS) treatment in water

Widespread per- and poly-fluoroalkyl substances (PFAS) contamination in water, sediments and soils has driven demand for scalable and cost-effective treatments suitable for application across a range of ∑PFAS concentrations from ng/L to mg/L. One promising class of treatment technology is based on PFAS accumulation at the surface of air bubbles. In this study, hydrodynamic cavitation induced by high shear mixing generated colloidal gas aphrons (CGAs) made of different surfactants (cationic, anionic and non-ionic) to facilitate separation of PFAS differing in carbon–fluorine chain length, head group and charge. Separation efficiency was evaluated for a 600 µg/L ∑PFAS mixture of 6 PFAS each at 100 µg/L, and also for a solution spiked to 1 mg/L ∑PFAS with an aqueous film forming foam (AFFF) mixture. The choice of surfactant produced CGAs with different bubble sizes and surface properties; the non-ionic surfactant produced significantly smaller bubbles, while the cationic and anionic surfactant varied principally by charge. The ∑PFAS separation efficiency varied from < 30 % to 86 % using different surfactants after a 30 s process. The non-ionic surfactant was most effective overall, and the cationic surfactant was most efficient for short-chain PFAS, and those with the carboxylic head group due to surface charge compatibility. Zwitterionic precursor PFAS and perfluoroalkyl sulfonic acids species tested in this study were removed with > 90 % efficiency when anionic and non-ionic surfactants formed the CGAs, while short-chain perfluoroalkyl acids PFAA were removed similarly effectively by cationic surfactant-derived CGAs. While separation efficiencies were lower than the > 95 % ∑PFAS reductions reported elsewhere, the effect was achieved with a treatment time of 30 s, in contrast to the significantly longer treatment cycles applied in other studies.

Exposure to per- and polyfluoroalkyl substances and alterations in plasma microRNA profiles in children

BackgroundPer- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans. ObjectiveTo investigate associations between PFAS concentrations and miRNA levels in children. MethodsData from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs. ResultsPlasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis. ConclusionThrough miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways.

Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

An in vitro model system for testing chemical effects on microbiome-immune interactions - examples with BPX and PFAS mixtures.

More than 350,000 chemicals make up the chemical universe that surrounds us every day. The impact of this vast array of compounds on our health is still poorly understood. Manufacturers are required to carry out toxicological studies, for example on the reproductive or nervous systems, before putting a new substance on the market. However, toxicological safety does not exclude effects resulting from chronic exposure to low doses or effects on other potentially affected organ systems. This is the case for the microbiome-immune interaction, which is not yet included in any safety studies. A high-throughput in vitro model was used to elucidate the potential effects of environmental chemicals and chemical mixtures on microbiome-immune interactions. Therefore, a simplified human intestinal microbiota (SIHUMIx) consisting of eight bacterial species was cultured in vitro in a bioreactor that partially mimics intestinal conditions. The bacteria were continuously exposed to mixtures of representative and widely distributed environmental chemicals, i.e. bisphenols (BPX) and/or per- and polyfluoroalkyl substances (PFAS) at concentrations of 22 µM and 4 µM, respectively. Furthermore, changes in the immunostimulatory potential of exposed microbes were investigated using a co-culture system with human peripheral blood mononuclear cells (PBMCs). The exposure to BPX, PFAS or their mixture did not influence the community structure and the riboflavin production of SIHUMIx in vitro. However, it altered the potential of the consortium to stimulate human immune cells: in particular, activation of CD8+ MAIT cells was affected by the exposure to BPX- and PFAS mixtures-treated bacteria. The present study provides a model to investigate how environmental chemicals can indirectly affect immune cells via exposed microbes. It contributes to the much-needed knowledge on the effects of EDCs on an organ system that has been little explored in this context, especially from the perspective of cumulative exposure.

Positive Associations of Perfluoroalkyl and Polyfluoroalkyl Substances With Hypertension May Be Attenuated by Endogenous Sex Hormones: A Nationally Representative Cross-Sectional Study.

Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored. This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension. The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively. Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones.

Association between per- and polyfluoroalkyl substances with serum hepatobiliary system function biomarkers in patients with acute coronary syndrome

Previous studies have suggested that abnormal hepatobiliary system function may contribute to poor prognosis in patients with acute coronary syndrome (ACS) and that abnormal hepatobiliary system function may be associated with per- and polyfluoroalkyl substances (PFAS) exposure. However, there is limited evidence for this association in cardiovascular subpopulations, particularly in the ACS patients. Therefore, we performed this study to evaluate the association between plasma PFAS exposure and hepatobiliary system function biomarkers in patients with ACS. This study included 546 newly diagnosed ACS patients at the Second Hospital of Hebei Medical University, and data on 15 hepatobiliary system function biomarkers were obtained from medical records. Associations between single PFAS and hepatobiliary system function biomarkers were assessed using multiple linear regression models and restricted cubic spline model (RCS), and mixture effects were assessed using the Quantile g-computation model. The results showed that total bile acids (TBA) was negative associated with PFHxS (-7.69 %, 95 % CI: -12.15 %, -3.01 %). According to the RCS model, linear associations were found between TBA and PFHxS (P for overall =0.003, P for non-linear =0.234). We also have observed the association between between PFAS congeners and liver enzyme such as aspartate aminotransferase (AST) and α-l-Fucosidase (AFU), but it was not statistically significant after correction. In addition, Our results also revealed an association between prealbumin (PA) and PFAS congeners as well as mixtures. Our findings have provided a piece of epidemiological evidence on associations between PFAS congeners or mixture, and serum hepatobiliary system function biomarkers in ACS patients, which could be a basis for subsequent mechanism studies.

Identification and quantification of novel per- and polyfluoroalkyl substances (PFAS) contamination in a Great Lakes urban-dominated watershed

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic fluoro-compounds that are oil-, water-, and flame-resistant, making them useful in a wide range of commercial and consumer products, as well as resistant to environmental degradation. To assess the impact of urbanization and wastewater treatment processes, surface water and sediment samples were collected at 27 sites within the Great Lakes in the Lake Huron to Lake Erie corridor (HEC), an international waterway including the highly urbanized Detroit and Rouge Rivers. Samples were analyzed for 92 PFAS via UHPLC-MS/MS. Our previous data in the HEC found the highest amount of PFAS contamination at the Rouge River mouth. In addition to evaluating the input of the Rouge River into the HEC, we evaluated the transport of PFAS into the HEC from other major tributaries. PFAS were detected in both surface water and sediment at all sites in this study, with a total of 10 congeners quantified in all surface water samples and 16 congeners quantified in all sediment samples, indicating ubiquitous contamination. Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were pervasive in the HEC as these two compounds were detected in all sites and matrices, often at concentrations above the US EPA's recommended lifetime interim updated health advisories. Surface water samples contained more perfluorohexanoic acid (PFHxA) than any other congener, with average aqueous PFHxA across all surface water samples exceeding the average concentration previously reported in the Great Lakes. Sediment samples were dominated by PFOS, but novel congeners, notably 3-Perfluoropentyl propanoic acid (FPePA), were also quantified in sediment. The Rouge River and other tributaries contribute significantly to the PFAS burden in the HEC including Lake Erie. Overall, our results indicate the need for expanding toxicological research and risk assessment focused on congeners such as PFHxA and PFAS mixtures, as well as regulation that is tighter at the onset of production and encompasses PFAS as a group at a national level.

Considerations and challenges in support of science and communication of fish consumption advisories for per- and polyfluoroalkyl substances.

Federal, state, tribal, or local entities in the United States issue fish consumption advisories (FCAs) as guidance for safer consumption of locally caught fish containing contaminants. Fish consumption advisories have been developed for commonly detected compounds such as mercury and polychlorinated biphenyls. The existing national guidance does not specifically address the unique challenges associated with bioaccumulation and consumption risk related to per- and polyfluoroalkyl substances (PFAS). As a result, several states have derived their own PFAS-related consumption guidelines, many of which focus on one frequently detected PFAS, known as perfluorooctane sulfonic acid (PFOS). However, there can be significant variation between tissue concentrations or trigger concentrations (TCs) of PFOS that support the individual state-issued FCAs. This variation in TCs can create challenges for risk assessors and risk communicators in their efforts to protect public health. The objective of this article is to review existing challenges, knowledge gaps, and needs related to issuing PFAS-related FCAs and to provide key considerations for the development of protective fish consumption guidance. The current state of the science and variability in FCA derivation, considerations for sampling and analytical methodologies, risk management, risk communication, and policy challenges are discussed. How to best address PFAS mixtures in the development of FCAs, in risk assessment, and establishment of effect thresholds remains a major challenge, as well as a source of uncertainty and scrutiny. This includes developments better elucidating toxicity factors, exposures to PFAS mixtures, community fish consumption behaviors, and evolving technology and analytical instrumentation, methods, and the associated detection limits. Given the evolving science and public interests informing PFAS-related FCAs, continued review and revision of FCA approaches and best practices are vital. Nonetheless, consistent, widely applicable, PFAS-specific approaches informing methods, critical concentration thresholds, and priority compounds may assist practitioners in PFAS-related FCA development and possibly reduce variability between states and jurisdictions. Integr Environ Assess Manag 2024;20:1839-1858. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Per- and Polyfluoroalkyl Substances May Be Correlated With Chlamydia trachomatis: Data From the National Health and Nutrition Examination Survey 2003-2016.

Per- and polyfluoroalkyl substances (PFAS) alter immune function increasing infectious diseases risk. We examined the relationship between PFAS and chlamydia. A total of 3965 nonpregnant adults ages 18-39 years from the National Nutrition Examination Survey 2003-2016 cycles were included. Poisson regression with robust error variance estimated the prevalence ratio and 95% confidence intervals for the association between PFAS and chlamydia. A g computation model was used to examine PFAS mixtures and chlamydia. In adjusted age and sex-stratified models, an increase in PFAS mixtures by one quintile was associated with chlamydia in older males and younger females. Associations were not observed before stratification. PFAS exposure associated with higher chlamydia prevalence, but only in stratified models suggesting biological differences by gender and age. However, small sample sizes could have affected the precision of our models.

Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Associations between per- and polyfluoroalkyl chemicals and abdominal aortic calcification in middle-aged and older adults

IntroductionPer- and polyfluoroalkyl substances (PFAS) have infiltrated countless everyday products, raising concerns about potential effects on human health, specifically on the cardiovascular system and the development of abdominal aortic calcification (AAC). However, our understanding of this relationship is still limited. ObjectivesThis study aims to investigate the effects of PFAS on AAC using machine learning algorithms. MethodsLeveraging the power of machine learning (ML) technique, extreme gradient boosting (XGBoost), we assessed the relationship between PFAS exposure and AAC risk. We focused on three PFAS compounds, perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) through multiple logistic regression, restricted cubic spline (RCS), and quantile g-computation (QGC) models. To get more insight into the underlying mechanisms, mediation analyses are used to investigate the potential mediating role of fatty acids and blood cell fractions in AAC. ResultsOur findings indicate that elevated serum levels of PFHxS and PFDeA are associated with the increased risk of AAC. The QGC analyses underscore the overall positive association between the PFAS mixture and AAC risk, with PFHxS carrying the greatest weight, followed by PFDeA. The RCS analyses reveal a dose-dependent increase between serum PFHxS concentration and AAC risk in an inverted V-shape way. Moreover, age and PFHxS exposure are identified as the primary factors contributing to abdominal aortic calcification risk in SHapley Additive exPlanation (SHAP) summary plot combined with XGBoost technique. Although PFAS significantly change the profile of fatty acids, we do not find any mediating roles of them in AAC. Despite strong associations between PFAS exposure and hematological indicators, our analysis does not find evidence that these indicators mediate the development of AAC. ConclusionsIn summary, our study highlights the detrimental impact of PFAS on abdominal aortic health and emphasizes the need for further research to understand the underlying mechanisms involved.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. ObjectivesThis study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. MethodsThe study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. ResultsThe molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: −12.21, −0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: −18.33, −0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. ConclusionsIncreased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

Individual and joint associations of per- and polyfluoroalkyl substances (PFAS) with gallstone disease in adults: A cross-sectional study

Disturbances in the enterohepatic circulation are important biological mechanisms for causing gallstones and also have important effects on the metabolism of Per- and polyfluoroalkyl substances (PFAS). Moreover, PFAS is associated with sex hormone disorder which is another important cause of gallstones. However, it remains unclear whether PFAS is associated with gallstones. In this study, we used logistic regression, restricted cubic spline (RCS), quantile g-computation (qg-comp), Bayesian kernel machine regression (BKMR), and subgroup analysis to assess the individual and joint associations of PFAS with gallstones and effect modifiers. We observed that the individual associations of perfluorodecanoic acid (PFDeA) (OR: 0.600, 95% CI: 0.444 to 0.811), perfluoroundecanoic acid (PFUA) (OR: 0.630, 95% CI: 0.453 to 0.877), n-perfluorooctane sulfonic acid (n-PFOS) (OR: 0.719, 95% CI: 0.571 to 0.906), and perfluoromethylheptane sulfonic acid isomers (Sm-PFOS) (OR: 0.768, 95% CI: 0.602 to 0.981) with gallstones were linearly negative. Qg-comp showed that the PFAS mixture (OR: 0.777, 95% CI: 0.514 to 1.175) was negatively associated with gallstones, but the difference was not statistically significant, and PFDeA had the highest negative association. Moreover, smoking modified the association of perfluorononanoic acid (PFNA) with gallstones. BKMR showed that PFDeA, PFNA, and PFUA had the highest groupPIP (groupPIP = 0.93); PFDeA (condPIP = 0.82), n-perfluorooctanoic acid (n-PFOA) (condPIP = 0.68), and n-PFOS (condPIP = 0.56) also had high condPIPs. Compared with the median level, the joint association of the PFAS mixture with gallstones showed a negative trend; when the PFAS mixture level was at the 70th percentile or higher, they were negatively associated with gallstones. Meanwhile, when other PFAS were fixed at the 25th, 50th, and 75th percentiles, PFDeA had negative associations with gallstones. Our evidence emphasizes that PFAS is negatively associated with gallstones, and more studies are needed in the future to definite the associations of PFAS with gallstones and explore the underlying biological mechanisms.

Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones

Background/AimsPregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development. MethodsIn Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp). ResultsInterquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: −0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: −5.7; 95%CI: −10.3, −0.8, and %Δ: −4.1; 95%CI: −7.6, −0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: −5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: −7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: −9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: −17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: −16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: −3.7, 20.9). ConclusionPFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings.

Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women

BackgroundPer- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes. ObjectiveIn a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations. MethodsWe analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders. ResultsBaseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (β = 0.03; 95 % CrI = 0.20, 0.25), 50th (β = 0.02; 95 % CrI = -0.16, 0.19), and 90th (β = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture. ConclusionIn this prospective cohort study, PFAS concentrations—assessed individually or as a mixture—were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with hypertensive disorders of pregnancy in the Atlanta African American Maternal-Child cohort

BackgroundPer- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. MethodsParticipants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. ResultsThe geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. ConclusionsIn this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.

Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003–2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.

Exposure to per- and polyfluoroalkyl substances in lung cancer patients and their associations with clinical health indicators

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27–152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.