Perfluorononanoic Acid Concentrations Research Articles

Environmentally relevant concentration PFNA promotes degradation of SMAD7 to drive progression of ovarian cancer via TGF-β/SMADs signaling pathway

Perfluorononanoic acid (PFNA), an acknowledged environmental endocrine disruptor, is increasingly utilized as a substitute for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Despite its growing use, limited research has been conducted to investigate its potential impact on tumorigenesis and progression, and the potential molecular mechanisms. Earlier studies linked perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to breast and gynecological cancer progression in humans, lacking a clear understanding of the underlying mechanisms, notably in ovarian cancer. Our investigation into PFNA's effects at environmental concentrations (0.25–2 mM) showed no significant impact on cell proliferation but a notable increase in invasion and migration of ovarian cancer cells. This led to alterations in epithelial-mesenchymal transition (EMT) markers, including Claudin1, Vimentin, and Snail. Notably, PFNA exposure activated the TGF-β/SMADs signaling pathway. Crucially, SMAD7 degradation through the ubiquitin-proteasome system emerged as PFNA's pivotal molecular target for inducing EMT, corroborated in mouse models. In summary, this study presented evidence that environmentally relevant concentrations of PFNA could induce SMAD7 degradation via the proteasome pathway, subsequently activating the TGF-β/SMADs signaling pathway, and promoting EMT in ovarian cancer. These results illuminated the association between PFNA exposure and metastasis of ovarian cancer.

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.

Temporal trends of per- and polyfluoroalkyl substances concentrations: Insights from Australian human biomonitoring 2002–2021 and the U.S. NHANES programs 2003–2018

Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) are persistent contaminants detected in human blood worldwide, raising significant health concerns. In response, countries such as the United States and Australia have implemented regulatory measures to limit their use. This study analysed temporal trends in serum concentrations of these four PFAS and how these trends align with regulatory measures, using data from NHANES (2003–2004 to 2017–2018) and the Australian Human Biomonitoring Program (2002–2003 to 2020–2021). Multiple regression analyses adjusted for age and gender were performed to estimate mean concentration changes over time, and differences within each dataset were assessed. Results indicated significant reductions (p < 0.001) in PFOS, PFOA, and PFHxS concentrations post-2002-2003, while PFNA concentrations increased until 2009–2010 before declining in both Australia and the U.S. Age-related trends in the U.S. during the last monitoring period showed higher PFAS concentrations in the oldest age groups, while in Australia, this trend was evident for PFOS and PFHxS. In Australia, the age group of 0–5 years had PFOA and PFNA concentrations similar to those of adults over 46 years, indicating ongoing exposure. Gender differences were consistent in both programs, with females aged 6–15, 31–45, and 46–60 years exhibiting lower serum concentrations, particularly in the 31–45 years age group. These findings support Australian and U.S. efforts to reduce PFAS exposure through regulatory actions, highlight the need to address ongoing exposure in young children, and consider gender-specific factors affecting PFAS concentrations.

Per- and polyfluoroalkyl substances and bone mineral content in early adolescence: Modification by diet and physical activity

BackgroundPer- and polyfluoroalkyl substance (PFAS) exposures may negatively impact bone mineral accrual, but little is known about potential mitigators of this relation. We assessed whether associations of PFAS and their mixture with bone mineral content (BMC) in adolescence were modified by diet and physical activity. MethodsWe included 197 adolescents enrolled in a prospective pregnancy and birth cohort in Cincinnati, Ohio (2003–2006). At age 12 years, we collected serum for PFAS measurements and used dual-energy x-ray absorptiometry to measure BMC. We calculated dietary calcium intake and Health Eating Index (HEI) scores from repeated 24-h dietary recalls, physical activity scores using the Physical Activity Questionnaire for Older Children (PAQ-C), and average moderate to vigorous physical activity (MVPA) based on accelerometry. We estimated covariate-adjusted differences in BMC z-scores per interquartile range (IQR) increase of individual PFAS concentrations using linear regression and per simultaneous IQR increase in all four PFAS using g-computation. We evaluated effect measure modification (EMM) using interaction terms between each modifier and PFAS. ResultsHigher serum perfluorooctanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid concentrations and the PFAS mixture were associated with lower BMC z-scores. An IQR increase in all PFAS was associated with a 0.27 (−0.54, 0.01) lower distal radius BMC z-score. Associations with lower BMC were generally stronger among adolescents classified as < median for calcium intake, HEI scores, or MVPA compared to those ≥ median. The difference in distal radius BMC z-score per IQR increase in all PFAS was −0.38 (−0.72, −0.04) for those with <median calcium intake versus −0.03 (−0.48, 0.35) for ≥ median (EMM p-value = 0.16); the corresponding differences by MVPA were −0.42 (−0.76, −0.07) for < median and −0.05 (−0.42, 0.32) for ≥ median (EMM p-value = 0.13). ConclusionHealthy, calcium-rich diets and higher intensity physical activity may mitigate the adverse impact of PFAS on adolescent bone health.

Fluorine mass balance analysis in wild boar organs from the Bohemian Forest National Park

Wild boars have been reported as bioindicators for per- and polyfluoroalkyl substances (PFAS) in a variety of studies. However, data about PFAS levels in wild boars from sites with limited industrial and general human activity is scarce. In this study, wild boar (Sus scrofa) organs from the Bohemian Forest National Park (Czech Republic) were used as bioindicators for PFAS pollution. In this work, 29 livers and 24 kidneys from 30 wild boars (0.5–5 years) were investigated using a fluorine mass balance approach. For this, the samples were measured using high performance liquid chromatography with electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS), targeting 30 PFAS, including legacy and replacement PFAS, direct total oxidisable precursor assay (dTOPA) and combustion ion chromatography (CIC). Perfluorocarboxylic acids (PFCAs) from C7 to C14 and perfluorooctanesulfonic acid (PFOS) were detected in >50 % of samples. In the livers, PFCAs dominated the profile with median concentrations of 230 μg/kg for perfluorononanoic acid (PFNA) and 75 μg/kg perfluorooctanoic acid (PFOA). PFOA and PFNA concentrations in the livers were one order of magnitude higher than in livers from wild boars caught in rural NE Germany considered as background concentration. PFOS in liver contributed only 30 % to the Σc(PFASTarget) with a median concentration of 170 μg/kg. Kidneys and livers contain an average of 2460 μg F/kg and 6800 μg F/kg extractable organic fluorine (EOF) respectively. Σc(PFASTarget) add up to a maximum of 10 % of the extractable organic fluorine. After oxidisation of the samples, PFOA, PFNA and Σc(PFASdTOPA) increased in livers, but could not explain the EOF. The elevated concentration of PFOA and PFNA may indicate differences in biomagnification for different habitats or an unidentified PFAS source in proximity to the national park.

Association of per- and polyfluoroalkyl substances (PFAS) with periodontitis: the mediating role of sex hormones

ObjectivesTo investigate the association between serum per- and polyfluoroalkyl substances (PFAS) and periodontitis, and further explore the possible mediating role of sex hormones in this association.MethodsWe extracted data from National Health and Nutrition Examination Survey (NHANES) 2009–2014. Univariable and multivariable logistic regression models were performed to investigate the association between serum levels of seven PFASs and periodontitis. Bayesian kernel machine regression (BKMR) was conducted to assess the joint effect of PFASs in mixtures. Mediation analyses were used to explore the potential mediating role of sex hormones.ResultsParticipants with periodontitis had higher concentrations of serum perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) than those without periodontitis (both P < 0.05). In fully adjusted models, high serum concentrations of PFOS and PFNA were positively associated with periodontitis (tertile 3 vs. tertile 1: prevalence ratio (PR) = 1.19 for PFOS, 95% CI: 1.01–1.39; PR = 1.17 for PFNA, 95% CI: 1.02–1.34). The results from the BKMR models consistently showed a positive association between PFAS mixtures and periodontitis. Of note, testosterone and the ratio of testosterone to estradiol significantly mediated the relationship between high level of PFOS and periodontitis, accounting for 16.5% and 31.7% of the total effect, respectively. Sensitivity analyses yielded similar results when using periodontal clinical indices (mean loss of attachment, mean periodontal probing depth, and the number of teeth) as dependent variables.ConclusionsThese findings provide evidence to support a positive association between certain PFASs and periodontitis, which might be partially mediated by sex hormones.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

Low concentrations of perfluoroalkyl acids (PFAAs) in municipal drinking water associated with serum PFAA concentrations in Swedish adolescents

While highly contaminated drinking water (DW) is a major source of exposure to perfluoroalkyl acids (PFAAs), the contribution of low-level contaminated DW (i.e. < 10 ng/L of individual PFAAs) to PFAA body burdens has rarely been studied. To address this knowledge gap, we evaluated the association between concentrations of perflurooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS), and their sum (∑4PFAAs) in DW and serum in Swedish adolescents using weighted least squares regression. We paired serum PFAA concentrations in adolescents (age 10–21 years, n = 790) from the dietary survey Riksmaten Adolescents 2016–17 (RMA) with mean PFAA concentrations in water samples collected in 2018 from waterworks (n = 45) supplying DW to the participant residential and school addresses. The median concentrations of individual PFAAs in DW were < 1 ng/L. Median concentrations of PFNA and PFHxS in serum were < 1 ng/g, while those of PFOA and PFOS were 1–2 ng/g. Significant positive associations between PFAA concentrations in DW and serum were found for all four PFAAs and ∑4PFAAs, with estimated serum/DW concentration ratios ranging from 210 (PFOA) to 670 (PFHxS), taking exposure from sources other than DW (background) into consideration. The mean concentrations of PFHxS and ∑4PFAA in DW that would likely cause substantially elevated serum concentrations above background variation were estimated to 0.9 ng/L and 2.4 ng/L, respectively. The European Food Safety Authority has determined a health concern concentration of 6.9 ng ∑4PFAAs/mL serum. This level was to a large degree exceeded by RMA participants with DW ∑4PFAA concentrations above the maximum limits implemented in Denmark (2 ng ∑4PFAAs/L) and Sweden (4 ng ∑4PFAAs/L) than by RMA participants with DW concentrations below the maximum limits. In conclusion, PFAA exposure from low-level contaminated DW must be considered in risk assessment for adolescents.

Folate concentrations and serum perfluoroalkyl and polyfluoroalkyl substance concentrations in adolescents and adults in the USA (National Health and Nutrition Examination Study 2003–16): an observational study

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a family of highly fluorinated aliphatic compounds, which are widely used in commercial applications, including food packaging, textiles, and non-stick cookware. Folate might counteract the effects of environmental chemical exposures. We aimed to explore the relationship between blood folate biomarker concentrations and PFAS concentrations. This observational study pooled cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2016 cycles. NHANES is a population-based national survey that measures the health and nutritional status of the US general population every 2 years by means of questionnaires, physical examination, and biospecimen collection. Folate concentrations in red blood cells and in serum, and perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) concentrations in serum were examined. We used multivariable regression models to assess the percentage change in serum PFAS concentrations in relation to changes in folate biomarker concentrations. We additionally used models with restricted cubic splines to investigate the shape of these associations. This study included 2802 adolescents and 9159 adults who had complete data on PFAS concentrations, folate biomarkers, and covariates, were not pregnant, and had never had a cancer diagnosis at the time of the survey. The mean age was 15·4 years (SD 2·3) for adolescents and 45·5 years (17·5) for adults. The proportion of male participants was slightly higher in adolescents (1508 [54%] of 2802 participants) than in adults (3940 [49%] of 9159 participants). We found negative associations between red blood cell folate concentrations and serum concentrations of PFOS (percentage change for a 2·7 fold-increase in folate level -24·36%, 95% CI -33·21 to -14·34) and PFNA (-13·00%, -21·87 to -3·12) in adolescents, and PFOA (-12·45%, -17·28 to -7·35), PFOS (-25·30%, -29·67 to -20·65), PFNA (-21·65%, -26·19 to -16·82), and PFHxS (-11·70%, -17·32 to 5·70) in adults. Associations for serum folate concentrations and PFAS were in line with those found for red blood cell folate levels, although the magnitude of the effects was lower. Restricted cubic spline models suggested linearity of the observed associations, particularly for associations in adults. In this large-scale, nationally representative study, we found consistent inverse associations for most examined serum PFAS compounds in relation to folate concentrations measured in either red blood cells or serum among both adolescents and adults. These findings are supported by mechanistic in-vitro studies that show the potential of PFAS to compete with folate for several transporters implicated in PFAS toxicokinetics. If confirmed in experimental settings, these findings could have important implications for interventions to reduce the accumulated PFAS body burden and mitigate the related adverse health effects. United States National Institute of Environmental Health Sciences.

Dietary per- and polyfluoroalkyl substance (PFAS) exposure in adolescents: The HOME study

BackgroundDiet is the primary exposure pathway for per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations. Few studies have examined associations of dietary quality and macronutrient intake with PFAS exposure among US adolescents. ObjectiveTo assess relationships of self-reported dietary quality and macronutrient intake with serum PFAS concentrations in adolescents. MethodsWe used cross-sectional data from 193 Cincinnati, Ohio area adolescents (median age 12.3 years) collected from 2016 to 2019. Using 24-h food recalls completed by adolescents on three separate days, we derived Healthy Eating Index (HEI) scores, HEI components, and macronutrient intake. We measured perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations in fasting serum samples. Using linear regression, we estimated covariate-adjusted associations between dietary variables and serum PFAS concentrations. ResultsThe median HEI score was 44 and median serum PFOA, PFOS, PFHxS, and PFNA concentrations were 1.3, 2.4, 0.7, and 0.3 ng/mL respectively. In adjusted models, higher total HEI scores, whole fruit and total fruit HEI component scores, and total dietary fiber intake were associated with lower concentrations of all four PFAS. For example, serum PFOA concentrations were 7% lower (95% CI: −15, 2) per standard deviation increase in total HEI score and 9% lower (95% CI: −18, 1) per standard deviation increase in dietary fiber. SignificanceGiven adverse health effects associated with PFAS exposure, it is crucial to understand modifiable exposure pathways. Findings from this study may inform future policy decisions aiming to limit human exposure to PFAS.

Association between prenatal and early postnatal exposure to perfluoroalkyl substances (PFAS) and IQ score in 7-year-old children from the Odense Child Cohort.

Perfluoroalkyl substances (PFAS) are persistent chemicals capable of crossing the placenta and passing into breastmilk. Evidence suggests that PFAS exposure may affect brain development. We investigated whether prenatal or early postnatal PFAS exposure was associated with IQ-scores in schoolchildren from the Odense Child Cohort, Denmark 2010 to 2020. We assessed perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) concentrations in maternal serum collected in the 1st trimester of pregnancy and in child serum at age 18 months. At 7 years of age children completed an abbreviated version of Wechsler Intelligence Scale for Children version-V (WISC-V) from which Full Scale Intelligence Quotient (FSIQ) and Verbal Comprehension Index (VCI) were estimated. In multiple linear regressions among 967 mother-child pairs a doubling in maternal PFOS and PFNA concentrations was associated with lower FSIQ, while no significant associations were observed for PFOA, PFHxS or PFDA. PFAS concentrations at 18 months and duration of breastfeeding were strongly correlated and even in structural equation models it was not possible to differentiate the opposite effects of PFAS exposure and duration of breastfeeding on FSIQ. As PFAS exposure is ubiquitous association with even a small reduction in IQ is of public health concern.

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Childhood Autism-related Outcomes.

Epidemiologic evidence linking prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with altered neurodevelopment is inconclusive, and few large studies have focused on autism-related outcomes. We investigated whether blood concentrations of PFAS in pregnancy are associated with child autism-related outcomes. We included 10 cohorts from the National Institutes of Health (NIH)-funded Environmental influences on Child Health Outcomes (ECHO) program (n = 1,429). We measured 14 PFAS analytes in maternal blood collected during pregnancy; eight analytes met detection criteria for analysis. We assessed quantitative autism-related traits in children via parent report on the Social Responsiveness Scale (SRS). In multivariable linear models, we examined relationships of each PFAS (natural log-transformed) with SRS scores. We further modeled PFAS as a complex mixture using Bayesian methods and examined modification of these relationships by child sex. Most PFAS in maternal blood were not associated with child SRS T-scores. Perfluorononanoic acid (PFNA) showed the strongest and most consistent association: each 1-unit increase in ln-transformed PFNA was associated with greater autism-related traits (adjusted β [95% confidence interval (CI)] = 1.5 [-0.1, 3.0]). The summed mixture, which included six PFAS detected in >70% of participants, was not associated with SRS T-scores (adjusted β [95% highest posterior density interval] = 0.7 [-1.4, 3.0]). We did not observe consistent evidence of sex differences. Prenatal blood concentrations of PFNA may be associated with modest increases in child autism-related traits. Future work should continue to examine the relationship between exposures to both legacy and emerging PFAS and additional dimensional, quantitative measures of childhood autism-related outcomes.

Perfluorononanoic Acid Induces Neurotoxicity via Synaptogenesis Signaling in Zebrafish.

Perfluorononanoic acid (PFNA), commonly used as an alternative polyfluorinated compound (PFC) of perfluorooctanoic acid (PFOA), has been widely detected in the aquatic environment. Previous ecotoxicological and epidemiological results suggested that some neurobehavioral effects were associated with PFC exposure; however, the ecological impacts and underlying neurotoxicity mechanisms remain unclear, particularly in aquatic organisms during sensitive, early developmental stages. In this study, zebrafish embryos were exposed to environmentally relevant concentrations of PFNA for 120 h, and the neurological effects of PFNA were comprehensively assessed using transcriptional, biochemical, morphological, and behavioral assays. RNA sequencing and advanced bioinformatics analyses predicted and characterized the key biological processes and pathways affected by PFNA exposure, which included the synaptogenesis signaling pathway, neurotransmitter synapse, and CREB signaling in neurons. Neurotransmitter levels (acetylcholine, glutamate, 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and noradrenaline) were significantly decreased in zebrafish larvae, and the Tg(gad67:GFP) transgenic line revealed a decreased number of GABAergic neurons in PFNA-treated larvae. Moreover, the swimming distance, rotation frequency, and activity degree were also significantly affected by PFNA, linking molecular-level changes to behavioral consequences.

Plasma eicosapentaenoic acid, a biomarker of fish consumption, is associated with perfluoroalkyl carboxylic acid exposure in residents of Kyoto, Japan: a cross-sectional study.

Per- and polyfluoroalkyl substances (PFASs) are highly fluorinated organic compounds that have been widely used in industry during the past few decades. The main exposure routes for PFASs are thought to be the diet, drinking water, and dust. In this study, we aimed to evaluate the relationship between perfluoroalkyl carboxylic acids (PFCAs, members of the PFAS family) and the plasma eicosapentaenoic acid-to-arachidonic acid ratio (EPA/AA), a biological indicator of seafood intake, to determine whether seafood intake may represent a means of exposure to PFASs in the Japanese population. We performed a cross-sectional study using 131 plasma samples collected from residents of Kyoto, Japan in 2013 and held in the Kyoto University biological sample bank. The concentrations of perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), EPA, and AA were quantified by gas chromatography-mass spectrometry, and multiple linear regression was used to analyze the results. In multiple linear regression analyses with age and eGFR, PFOA showed a significant positive linear association with age (p = 0.0005); PFHpA showed a significant negative linear association with estimated glomerular filtration rate (eGFR; p = 0.0338); and PFHpA, PFOA, PFNA, PFUnDA, and PFDoDA exhibited significant positive linear associations with EPA/AA (p = 0.0358, 0.0056, 0.0242, <0.0001, and <0.0001, respectively). Because only PFHpA and PFOA were associated with smoking, their concentrations were examined again with smoking variable included and neither showed an association with smoking habit. PFOA showed a significant linear association with EPA/AA ratio (p = 0.0072), but PFHpA did not (p = 0.051). The plasma concentrations of PFOA, PFNA, PFUnDA and PFDoDA significantly associated with the EPA/AA ratio in residents of Kyoto.

Co-variate adjusted associations between serum concentrations of selected perfluoroalkyl substances and urinary concentrations of selected arsenic species.

Data from National Health and Nutrition Examination Survey for 2011-2012 were used to estimate associations of the serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluoroundecanoic acid (PFUnDA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA) with urinary concentrations of total arsenic (UAS), inorganic arsenic (IAS), arsenobetaine (UAB), and dimethyl arsinic acid (UDMA) among US adults aged > = 20years. Concentrations of PFNA were positively associated with all four arsenic variables but statistical significance was observed for IAS only (β = 0.33364, P = 0.04). Concentrations of PFDA were positively associated with UAS (β = 0.20688, P = 0.01), IAS (β = 0.23712, P = 0.02), and UAB (β = 0.26049, P = 0.02). Concentrations of PFUnDA were positively associated with UAS (β = 0.49946, P < 0.01), IAS (β = 0.51782, P < 0.01), UAB (β = 0.62924, P < 0.01), and UDMA (β = 0.26375, P < 0.01). Concentrations of Me-PFOSA with PFAS were inversely associated with every PFAS but statistical significance was observed for UDMA only (β = - 0.05613, P = 0.03). PFOA, PFHxS, and PFOS were, in general, negatively associated with concentrations of all four arsenic variables but without reaching statistical significance. Positive associations of PFDA, PFNA, and PFUnDA with arsenic necessitate investigation about impact of the co-exposure of these PFAS with arsenic and their impact on health. Fluorinated carbon chain length > 8 as opposed to ≤ 8 may have a role in defining associations of PFAS with arsenic.

Sublethal Exposure of Per- and Polyfluoroalkyl Substances of Varying Chain Length and Polar Functionality Results in Distinct Metabolic Responses in Daphnia magna.

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants used in industrial applications because of their physicochemical properties, which results in their ubiquitous presence across environmental matrices. To date, legacy PFAS have been well studied; however, the concentration of alternative PFAS may exceed the concentration of legacy pollutants, and more information is needed regarding the sublethal toxicity at the molecular level of aquatic model organisms, such as Daphnia magna. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) are four widely detected PFAS alternatives of varying chain length and polar functionality that are quantified in aquatic environments. The present study examines the metabolic perturbations of PFAS with varying chemistries to D. magna using targeted mass spectrometry-based metabolomics. Daphnia were acutely exposed to sublethal concentrations of PFBA, PFHxA, PFHxS, and PFNA before the polar metabolite profile was extracted from single organisms. Multivariate analysis demonstrated significant separation between the sublethal concentrations of PFHxA, PFHxS, and PFNA relative to the controls; in sum, longer chain lengths demonstrated greater overall perturbations to the extracted metabolic profiles. Univariate statistics revealed significant perturbations in the concentrations of several amino acids, nucleotides/nucleosides, and neurotransmitters with exposure to PFAS. These metabolic perturbations are consistent with disruptions in energy metabolism (pantothenate and coenzyme A metabolism, histidine metabolism) and protein synthesis (aminoacyl-transfer RNA biosynthesis and amino acid metabolism), which were identified through biochemical pathway analysis. These results provide evidence that although PFAS chemistry (chain length and polar functional group) invokes unique metabolic responses, there is also an underlying toxic mode of action that is common with select PFAS exposure. Overall, the present study highlights the capabilities of environmental metabolomics to elucidate the molecular-level perturbations of pollutants within the same chemical class to model aquatic organisms, which can be used to prioritize risk assessment of substituted PFAS alternatives. Environ Toxicol Chem 2023;42:242-256. © 2022 SETAC.

Plasma concentrations of perfluoroalkyl acids and their determinants in youth and adults from Nunavik, Canada

Perfluoroalkyl acids (PFAAs), a subset of per- and poly-fluoroalkyl substances (PFAS), are environmentally stable, mobile and bioaccumulative compounds. This leads to high concentrations in wildlife species essential to the cultural identity and subsistence of Arctic populations. Our objective was to characterize the distribution and exposure determinants of PFAAs among Nunavik Inuit adults. The study included up to 1322 Nunavik residents aged 16–80 years who participated in the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017). Plasma concentrations were compared to those the general Canadian population using data from the Canadian Health Measures Survey Cycle 5 (2016–2017). Associations between plasma concentrations of nine PFAAs, determined by liquid chromatography-tandem mass spectrometry, and sociodemographic factors and traditional activity participation were examined using multiple linear regression models. Overall exposure to PFAAs was twice as high compared to the general Canadian population and less regulated perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) concentrations were 7-fold higher, and perfluorodecanoic acid (PFDA) concentrations were 4-fold higher. Males had higher concentrations of perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS), whereas females had higher concentrations of PFDA and PFUnDA. PFAAs concentrations increased with age and were highest among those aged 60+ years. PFNA and PFOA concentrations followed a J-shaped pattern: those aged 16–29 years had higher concentrations than those aged 20–29 and 30–39 years. Ungava Bay generally had lower concentrations of all PFAAs congeners compared to Hudson Bay and Hudson Strait, with the exception of PFNA, which tended to have the lowest concentration in Hudson Strait. PFAAs concentrations were highly associated with hunting activity, omega-3 polyunsaturated fatty acids, and drinking water from environmental sources. The results highlight the importance of characterizing PFAAs exposure sources in Arctic communities and provide further evidence for the long-range transport of long-chain PFAAs and their precursors that necessitate international action.

Association between perfluoroalkyl substances concentration and bone mineral density in the US adolescents aged 12-19 years in NHANES 2005-2010.

BackgroundReports on the association of perfluoroalkyl substances (PFASs) exposure with adolescent bone health are scarce, and studies have primarily targeted maternal serum.ObjectiveWe evaluated the relationship between autologous serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) levels and bone mineral density (BMD) in adolescents.MethodsWe analyzed data from 1228 adolescents aged 12-19 years in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 and used multiple regression analysis to identify the relationship between serum PFOA, PFOS, PFHxS, and PFNA concentrations and total femur, femoral neck, and lumbar spine BMD, in addition to multiple stratified subgroup analyses.ResultsThe mean age of participants was 15 years, males had higher serum PFAS concentrations than females. The results of multiple regression analysis showed that the natural log(ln)-transformed serum PFOA, PFOS, and PFNA concentrations were negatively correlated with total femur, femoral neck, and lumbar spine BMD (all p < 0.05), and ln-PFHxS was positively correlated with total femur and femoral neck BMD (all p< 0.05). In males, ln-PFOA was negatively associated with total femur and lumbar spine BMD (all p< 0.05), ln-PFOS was associated with the reduced total femur, femoral neck, and lumbar spine BMD (all p< 0.05), while ln-PFHxS and ln-PFNA were not observed to correlate with BMD at these three sites. In females, both ln-PFOA and ln-PFOS were negatively correlated with total femur and lumbar spine BMD (all p< 0.05), ln-PFHxS is associated with the increased total femur and femoral neck BMD (all p< 0.05), and ln-PFNA was negatively correlated with total femur and femoral neck BMD (all p< 0.05), most of the associations were confined to females. The associations of ln-PFOS with femoral neck BMD and ln-PFNA with total femur BMD were more significant in those who were overweight/obese and had anemia, respectively (all p for interaction < 0.05).ConclusionsIn this representative sample of US adolescents aged 12-19 years, certain PFAS were associated with lower bone mineral density, and most of the associations were confined to females. The negative effect of PFAS on BMD is more pronounced in those who are overweight/obese and have anemia. However, further studies are needed to confirm this finding.

Elevated exposure to long-chain perfluoroalkyl and polyfluoroalkyl substances (PFAS) in Inuit from Nunavik, Arctic Canada: a call for global action

BACKGROUND AND AIM: The Inuit of Nunavik are exposed to perfluoroalkyl acids (PFAAs) via long-rang transport from southern to northern latitudes and biomagnification of PFAAs in Arctic food webs. Our objective was to document plasma PFAAs levels and compare them to previously documented levels and the general Canadian population. METHODS: The study included 1326 Nunavimmiut aged 16-82 years from the population representative survey, Qanuilirpitaa? 2017 Nunavik Inuit Health Survey. Concentrations of nine PFAAs were assessed, including perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUdA). Concentrations were compared to Nunavik levels in 2004, other Arctic regions, and the Canadian Health Measures Survey (CHMS) Cycle 5 2016-2017. Multiple linear regression analyses compared concentrations by demographics and lifestyle. RESULTS: There were elevated concentrations of various PFAAs congeners compared to CHMS, including PFOS, and long-chain PFAS congeners, PFNA, PFDA, and PFUnDA. PFNA and PFUdA concentrations were 7-fold higher than the CHMS concentrations, and PFDA concentrations were almost 4-fold higher than the CHMS concentrations. Short-chain congeners were largely undetected. Concentrations differed by sex, age, region, and indicators of seafood and marine mammal consumption. Males had higher concentrations of PFOA and PFHxS, whereas females had higher concentrations of PFDA and PFUdA. PFAAs concentrations increased with age and were highest among those aged 50+ years, such that serum PFOS concentrations were 2.5 times higher in those aged 50+ years compared to those aged 16-29 years. PFNA concentrations followed a U-shaped curve with increasing age. CONCLUSIONS: Our findings indicate a decrease in older PFAAs, but concentrations of many PFAAs in Nunavik remain several-fold higher compared to the general Canadian population. Evidence also points to an increase in exposure to long-chain PFAAs, which are an emerging public health concern in the Arctic. KEYWORDS: PFAS, Indigenous, Environmental justice, Exposure

Association between serum per- and polyfluoroalkyl substances concentrations and common cold among children and adolescents in the United States.

Per- and polyfluoroalkyl substances (PFAS) exert immunosuppressive effects in experimental animals. Few epidemiologic studies investigated PFAS exposure and immune-related clinical outcomes such as common cold, especially during childhood when the immune system is developing. This study used data from the National Health and Nutrition Examination Survey and included 517 children 3-11years (2013-2014 cycle) and 2732 adolescents 12-19years (2003-2016 cycles). Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were quantified. Common cold was self-reported by the participant or parent as having a head cold or chest cold in the last month. Multivariable logistic regression models were applied to examine the covariate-adjusted odds ratios (ORs) between individual PFAS concentrations and common cold incidence in the past month. The joint effect of PFAS mixtures was evaluated using Probit Bayesian Kernel Machine Regression (BKMR). A doubling of serum PFHxS concentration was associated with a 31% higher odds (OR=1.31, 95% CI: 1.06, 1.62) of common cold among children. Serum PFNA (OR=1.36, 95% CI: 0.93, 1.98) and PFOA (OR=1.32, 95% CI: 0.67, 2.62) concentrations were also related to common cold among children, as were serum PFOS concentrations among adolescents (OR=1.13, 95% CI: 0.96, 1.32). ORs were higher in male than female children and adolescents. BKMR showed a clear increasing trend of common cold estimates across quantiles of the total PFAS mixture concentration among children, while no obvious pattern emerged in adolescents. Among children in the United States, serum concentrations of PFAS mixtures, especially PFHxS and PFNA, were associated with higher odds of common cold. Among adolescents, PFOS was associated with increased common cold in the last month. This study contributes to the existing evidence supporting the immunotoxicity of PFAS in childhood and adolescence.