Serum Perfluorooctane Sulfonate Concentrations Research Articles

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.

Exposure Trends and Half-lives of Per- and Polyfluoroalkyl Substances (PFAS) in Australian Firefighters

BACKGROUND AND AIM: Per- and polyfluoroalkyl substances (PFASs) are persistent manmade compounds used in aqueous film forming foam (AFFF). The extensive use of AFFF has led to widespread environmental PFAS contamination and exposures to firefighters. The aim of this study is to determine PFAS blood serum concentration trends and apparent serum elimination half-lives in firefighters after the replacement of AFFF. METHODS: Current and former employees of an Australian corporation providing aviation firefighting services, where AFFF had been used in the past, were recruited to participate in this study. Special focus was placed on re-recruiting participants who had provided blood samples five years prior. Participants were asked to provide a blood sample and complete a questionnaire. Serum samples were analysed for 40 different PFASs using HP LC-MS/MS. RESULTS: A total of 799 participants provided blood samples. Of these, 130 previously provided blood serum five years prior. Mean serum concentrations of perfluorooctane sulfonate (PFOS, 27 ng/mL), perfluoroheptane sulfonate (PFHpS, 1.7 ng/mL) and perfluorohexane sulfonate (PFHxS, 14 ng/mL) were significantly higher than the levels in the general Australian population. Serum concentrations were associated with the use of PFOS/PFHxS based AFFF. Participants who commenced service after the replacement of this foam had serum concentrations similar to those in the general Australian population. Average individual apparent half-lives were estimated to be 5.0 years (perfluorooctanoic acid (PFOA)), 7.8 years (PFHxS), 7.4 years (PFHpS) and 6.5 years (PFOS). CONCLUSIONS: This study shows how workplace interventions such as replacement of AFFF, can benefit employees at risk of occupational exposure. KEYWORDS: Biological Monitoring Occupational Exposure Firefighters Follow-Up Studies Half-Life

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

Serum concentration trends and apparent half-lives of per- and polyfluoroalkyl substances (PFAS) in Australian firefighters.

Per- and polyfluoroalkyl substances (PFASs) are persistent manmade compounds used in aqueous film forming foam (AFFF). The extensive use of AFFF has led to widespread environmental PFAS contamination and exposures of firefighters. To determine PFAS blood serum concentration trends and apparent serum half-lives in firefighters after the replacement of AFFF. Current and former employees of an Australian corporation providing firefighting services, where AFFF formulations had been used since the 1980s up until 2010, were recruited in 2018-2019 to participate in this study. Special focus was put on re-recruiting participants who had provided blood samples five years prior (2013-2014). Participants were asked to provide a blood sample and fill in a questionnaire. Serum samples were analysed for 40 different PFASs using HP LC-MS/MS. A total of 799 participants provided blood samples in 2018-2019. Of these, 130 previously provided blood serum in 2013-2014. In 2018-2019, mean (arithmetic) serum concentrations of perfluorooctane sulfonate (PFOS, 27ng/mL), perfluoroheptane sulfonate (PFHpS, 1.7ng/mL) and perfluorohexane sulfonate (PFHxS, 14ng/mL) were higher than the levels in the general Australian population. Serum concentrations were associated with the use of PFOS/PFHxS based AFFF. Participants who commenced service after the replacement of this foam had serum concentrations similar to those in the general population. Mean (arithmetic) individual apparent half-lives were estimated to be 5.0 years (perfluorooctanoic acid (PFOA)), 7.8 years (PFHxS), 7.4 years (PFHpS) and 6.5 years (PFOS). This study shows how workplace interventions such as replacement of AFFF can benefit employees at risk of occupational exposure.

The role of mouse and human peroxisome proliferator-activated receptor-α in modulating the hepatic effects of perfluorooctane sulfonate in mice

Perfluorooctane sulfonate (PFOS) is a stable environmental contaminant that can activate peroxisome proliferator-activated receptor alpha (PPARα). In the present work, the specific role of mouse and human PPARα in mediating the hepatic effects of PFOS was examined in short-term studies using wild type, Ppara-null and PPARA-humanized mice. Mice fed 0.006 % PFOS for seven days (∼10 mg/kg/day), or 0.003 % PFOS for twenty-eight days (∼5 mg/kg/day), exhibited higher liver and serum PFOS concentrations compared to controls. Relative liver weights were also higher following exposure to dietary PFOS in all three genotypes as compared vehicle fed control groups. Histopathological examination of liver sections from mice treated for twenty-eight days with 0.003 % PFOS revealed a phenotype consistent with peroxisome proliferation, in wild-type and PPARA-humanized mice that was not observed in Ppara-null mice. With both exposures, expression of the PPARα target genes, Acox1, Cyp4a10, was significantly increased in wild type mice but not in Ppara-null or PPARA-humanized mice. By contrast, expression of the constitutive androstane receptor (CAR) target gene, Cyp2b10, and the pregnane X receptor (PXR) target gene, Cyp3a11, were higher in response to PFOS administration in all three genotypes compared to controls for both exposure periods. These results indicate that mouse PPARα can be activated in the liver by PFOS causing increased expression of Acox1, Cyp4a10 and histopathological changes in the liver. While histopathological analyses indicated the presence of mouse PPARα-dependent hepatic peroxisome proliferation in wild-type (a response associated with activation of PPARα) and a similar phenotype in PPARA-humanized mice, the lack of increased Acox1 and Cyp4a10 mRNA by PFOS in PPARA-humanized mice indicates that the human PPARα was not as responsive to PFOS as mouse PPARα with this dose regimen. Moreover, results indicate that hepatomegaly caused by PFOS does not require mouse or human PPARα and could be due to effects induced by activation of CAR and/or PXR.

Umbilical cord serum concentrations of perfluorooctane sulfonate, perfluorooctanoic acid, and the body mass index changes from birth to 5 1/2\xa0years of age

Prenatal exposure to perfluoroalkyl substances (PFAS) has been reported to affect body weight from birth to childhood, but the results remain inconclusive. We investigated whether umbilical cord blood concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are associated with children’s risk trajectory for obesity. 600 children were randomly selected from the Hamamatsu Birth Cohort for Mothers and Children (HBC study) and their umbilical cord serum PFAS concentrations were quantified. Participants underwent BMI measurements at ages 1, 4, 10, 18, 24, 32, 40, 50, and 66 months. Growth curve modeling with random intercept was performed with standardized BMI as outcome variable. PFOS was negatively associated with standardized BMI (β = − 0.34; p = 0.01), with a marginally significant interaction with the child’s age (β = 0.0038; p = 0.08). PFOA was negatively associated with standardized BMI (β = − 0.26, 95% CI − 0.51, 0; p = 0.05), with a significant interaction with the child’s age (β = 0.005; p = 0.01). Stratified analysis by sex revealed that these effects were significant only among girls. Prenatal exposure to PFAS initially was associated with lower standardized BMI during infancy, but this effect dissipated over time and reversed in direction during later childhood. The effects of prenatal PFAS on higher standardized BMI is stronger in girls.

Profiling of emerging and legacy per-/polyfluoroalkyl substances in serum among pregnant women in China.

Emerging per-/polyfluoroalkyl substances (PFASs), such as chlorinated polyfluorinated ether sulfonates (Cl-PFESAs), have been detected in human samples, yet investigation on their occurrence in pregnant women remains limited. Herein, ten legacy PFASs, branched perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), two Cl-PFESAs, perfluoro-2-propoxypropanoic acid (HFPO-DA), and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA) were detected in serum samples from 480 pregnant women in Tianjin, China. The influencing effects of age, body mass index, gravidity, and parity were also evaluated. PFOS [geographic mean (GM): 7.05ng/mL], 6:2Cl-PFESA (GM: 5.31ng/mL), and PFOA (GM: 2.82ng/mL) were the dominant PFASs in the serum of pregnant women, while neither HFPO-DA nor ADONA was detectable in any serum. The serum concentration of Cl-PFESAs and 6:2Cl-PFESA/PFOS ratio in the present study were 2-5 times higher than that in previous studies of pregnant women in China. Serum concentrations of Cl-PFESAs were significantly correlated with all detected PFAAs (Spearman's Rho: 0.15-0.69, p<0.01) excepting perfluoropentanesulfonate (PFPeS), indicating common exposure sources for Cl-PFESAs and PFAAs and some particular exposure source for PFPeS. Younger age and multi-parity were associated with lower serum concentrations of PFOS and several perfluoroalkyl sulfonates but not associated with Cl-PFESAs or PFOA, suggesting an increasing exposure to Cl-PFESAs and PFOA which neutralized the impact of age and parity. Overall, this study indicated a relatively high exposure level and composition of 6:2Cl-PFESA in pregnant women in the north coast of China, which highlights the need to investigate the exposure sources in this area.

Perfluoroalkyl substances, glucose homeostasis, and gestational diabetes mellitus in Chinese pregnant women: A repeat measurement-based prospective study

BackgroundExposure to perfluoroalkyl substances (PFASs) can affect glucose homeostasis and has been suggested as a potential risk of diabetes mellitus, but data are limited for pregnant women. ObjectivesWe aimed to explore the associations of exposure to PFASs with glucose homeostasis and gestational diabetes mellitus (GDM) in Chinese pregnant women. MethodsThe current study was conducted in Hebei Province of Northern China between 2013 and 2014 and 560 pregnant women were recruited in their early term of pregnancy and two representative serum PFASs, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), were measured. In 385 pregnant women who completed oral glucose tolerance test (OGTT), the associations of serum PFOA and PFOS concentrations with fasting blood glucose (FBG), fasting insulin (FIns), and homeostasis model assessment of insulin resistance (HOMA-IR) in the early, middle, and late terms of pregnancy and occurrence of GDM were examined using linear and Cox proportional hazard regression models. The reproducibility of serum PFASs during pregnancy was assessed in 230 pregnant women. ResultsThe intraclass correlation coefficients of serum PFASs, covariates, and outcomes based on averaged repeat measurement (0.35–0.96) were higher than those based on single measurement (0.16–0.92). Serum PFOA was positively associated with averaged FIns and HOMA-IR in the early, middle, and late terms of pregnancy and averaged blood glucose level at 1 h and 2 h of OGTT, but serum PFOS tended to be negatively associated with averaged FBG and OGTT blood glucose. The adjusted hazard ratios of GDM associated with serum PFOA and PFOS were 1.98 (95% confidence interval: 0.70–5.57; p-value: 0.197) and 0.71 (0.29–1.75; 0.453), respectively. ConclusionsOur data raised a possibility that exposure to PFASs might have different influences on glucose homeostasis and GDM in Chinese pregnant women. More lab and human studies are needed to further test the hypothesis and investigate potential mechanisms.

Airborne Precursors Predict Maternal Serum Perfluoroalkyl Acid Concentrations.

Human exposure to persistent perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), can occur directly from contaminated food, water, air, and dust. However, precursors to PFAAs (PreFAAs), such as dipolyfluoroalkyl phosphates (diPAPs), fluorotelomer alcohols (FTOHs), perfluorooctyl sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs), which can be biotransformed to PFAAs, may also be a source of exposure. PFAAs were analyzed in 50 maternal sera samples collected in 2007-2008 from participants in Vancouver, Canada, while PFAAs and PreFAAs were measured in matching samples of residential bedroom air collected by passive sampler and in sieved vacuum dust (<150 μm). Concentrations of PreFAAs were higher than for PFAAs in air and dust. Positive associations were discovered between airborne 10:2 FTOH and serum PFOA and PFNA and between airborne MeFOSE and serum PFOS. On average, serum PFOS concentrations were 2.3 ng/mL (95%CI: 0.40, 4.3) higher in participants with airborne MeFOSE concentrations in the highest tertile relative to the lowest tertile. Among all PFAAs, only PFNA in air and vacuum dust predicted serum PFNA. Results suggest that airborne PFAA precursors were a source of PFOA, PFNA, and PFOS exposure in this population.

Fate and redistribution of perfluoroalkyl acids through AFFF-impacted groundwater

Leaching of perfluoroalkyl acids (PFAAs) from a local point source, a fire-fighting training area, has led to extensive contamination of a groundwater aquifer which has spread underneath part of a nearby town, Oakey, situated in the State of Queensland, Australia. Groundwater is extracted by residents from privately owned wells for daily activities such as watering livestock and garden beds. The concentration of 10 PFAAs in environmental and biological samples (water, soil, grass, chicken egg yolk, serum of horses, cattle and sheep), as well as human serum was investigated to determine the extent of contamination in the town and discuss fate and redistribution of PFAAs. Perfluorooctane sulfonate (PFOS) was the dominant PFAA in all matrices investigated, followed by perfluorohexane sulfonate (PFHxS). PFOS concentrations measured in water ranged between <0.17–14μg/L, concentrations of PFHxS measured between <0.07–6μg/L. PFAAs were detected in backyards (soil, grass), livestock and chicken egg yolk. Significant differences (p<0.01) in PFOS and PFHxS concentrations in two groups of cattle were found, one held within the contamination plume, the other in the vicinity but outside of the contamination plume. In human serum PFOS concentrations ranged from 38 to 381μg/L, while PFHxS ranged from 39 to 214μg/L. Highest PFOS concentrations measured in human serum were >30-fold higher compared to the general Australian population. Through use of contaminated groundwater secondary sources of PFAA contamination are created on private property, leading to further redistribution of contamination and creation of additional human exposure pathways.

Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice.

The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD diet supplemented with 0.012% PFOS compared with those fed the control diet supplemented with 0.012% PFOS. Surprisingly, serum PFOS concentrations were higher while liver PFOS concentrations were lower in mMCD-fed mice compared with corresponding control-fed mice. To determine if supplemental dietary choline could prevent PFOS-induced hepatic effects, C57BL/6 mice were fed a control diet, or a choline supplemental diet (1.2%) with or without 0.003% PFOS. Lipidomic analysis demonstrated that PFOS caused alterations in hepatic lipid metabolism in the PFOS-fed mice compared with controls, and supplemental dietary choline prevented these PFOS-induced changes. Interestingly, dietary choline supplementation also prevented PFOS-induced oxidative damage. These studies are the first to suggest that PFOS may cause hepatic steatosis and oxidative stress by effectively reducing the choline required for hepatic VLDL production and export by forming an ion pair with choline, and suggest that choline supplementation may prevent and/or treat PFOS-induced hepatic steatosis and oxidative stress.

Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort.

Background:Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known.Objectives:We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth.Methods:We studied 1,507 mothers and their children from the Aarhus Birth Cohort (2008–2013). Nulliparous women were included during pregnancy, and serum levels of 16 PFAAs were measured between 9 and 20 completed gestational weeks (96% within 13 weeks). For compounds with quantifiable values in > 50% of samples (7 compounds), we report the associations with birth weight, birth length, and head circumference at birth determined by multivariable linear regression.Results:Estimated mean birth weights were lower among women with serum perfluorohexane sulfonate, perfluoroheptane sulfonate, and PFOS concentrations above the lowest exposure quartile, but we found no consistent monotonic dose–response patterns. These associations were stronger when the population was restricted to term births (n = 1,426). For PFOS, the birth weight estimates for the highest versus lowest quartile were –50 g (95% CI: –123, 23 g) in all births and –62 g (95% CI: –126, 3 g) in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth.Conclusions:Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those with exposures above the lowest quartile for some compounds.Citation:Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB. 2016. Perfluoroalkyl acids in maternal serum and indices of fetal growth: the Aarhus Birth Cohort. Environ Health Perspect 124:848–854; http://dx.doi.org/10.1289/ehp.1510046

Intra-Individual Differences in Serum Concentrations of PFOS and PFOA in Swedish Men between 1990/91 and 2002/03

BACKGROUND The knowledge about the intra-individual variations over time of the endocrine disruptors perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in the general populations is...

Fetal exposure to perfluorinated compounds and attention deficit hyperactivity disorder in childhood.

BackgroundThe association between exposure to perfluorinated compounds (PFCs) and attention deficit hyperactivity disorder (ADHD) diagnosis has been sparsely investigated in humans and the findings are inconsistent.ObjectivesA matched case-control study was conducted to investigate the association between fetal exposure to PFCs and ADHD diagnosis in childhood.MethodsThe study base comprised children born in Malmö, Sweden, between 1978 and 2000 that were followed up until 2005. Children with ADHD (n = 206) were identified at the Department of Child and Adolescent Psychiatry. Controls (n = 206) were selected from the study base and were matched for year of birth and maternal country of birth. PFC concentrations were measured in umbilical cord serum samples. The differences of the PFC concentrations between cases and controls were investigated using Wilcoxon's paired test. Possible threshold effects (above the upper quartile for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and above limit of detection [LOD] for perfluorononanoic acid (PFNA)) were evaluated by conditional logistic regression.ResultsThe median umbilical cord serum concentrations of PFOS were 6.92 ng/ml in the cases and 6.77 ng/ml in the controls. The corresponding concentrations of PFOA were 1.80 and 1.83 ng/ml. No associations between PFCs and ADHD were observed. Odds ratios adjusted for smoking status, parity, and gestational age were 0.81 (95% confidence interval [CI] 0.50 to 1.32) for PFOS, 1.07 (95% CI 0.67 to 1.7) for PFOA, and 1.1 (95% CI 0.75 to 1.7) for PFNA.ConclusionsThe current study revealed no support for an association between fetal exposure to PFOS, PFOA, or PFNA and ADHD.

Influenza Vaccine Response in Adults Exposed to Perfluorooctanoate and Perfluorooctanesulfonate

Supported by several epidemiological studies and a large number of animal studies, certain polyfluorinated alkyl acids are believed to be immunotoxic, affecting particularly humoral immunity. Our aim was to investigate the relationship between the antibody response following vaccination with an inactivated trivalent influenza vaccine and circulating levels of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS). The study population consisted of 411 adults living in the mid-Ohio region of Ohio and West Virginia where public drinking water had been inadvertently contaminated with PFOA. They participated in a larger cross-sectional study in 2005/2006 and were followed up in 2010, by which time serum levels of PFOA had been substantially reduced but were still well above those found in the general population. Hemagglutination inhibition tests were conducted on serum samples collected preinfluenza vaccination and 21 ± 3 days postvaccination in 2010. Serum samples were also analyzed for PFOA and PFOS concentrations (median: 31.5 and 9.2 ng/ml, respectively). Questionnaires were conducted regarding the occurrence and frequency of recent (during the last 12 months) respiratory infections. Our findings indicated that elevated PFOA serum concentrations are associated with reduced antibody titer rise, particularly to A/H3N2 influenza virus, and an increased risk of not attaining the antibody threshold considered to offer long-term protection. Although the direct relationship between weakened antibody response and clinical risk of influenza is not clear, we did not find evidence for an association between self-reported colds or influenza and PFOA levels nor between PFOS serum concentrations and any of the endpoints examined.

Breastfeeding: A Potential Excretion Route for Mothers and Implications for Infant Exposure to Perfluoroalkyl Acids

Background: The presence of perfluoroalkyl acids (PFAAs) in breast milk has been documented, but their lactational transfer has been rarely studied. Determination of the elimination rates of these chemicals during breastfeeding is important and critical for assessing exposure in mothers and infants.Objectives: We aimed to investigate the association between breastfeeding and maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). For a subset of the population, for whom we also have their infants’ measurements, we investigated associations of breastfeeding with infant serum PFAA concentrations.Methods: The present analysis included 633 women from the C8 Science Panel Study who had a child < 3.5 years of age and who provided blood samples and reported detailed information on breastfeeding at the time of survey. PFAA serum concentrations were available for all mothers and 8% (n = 49) of the infants. Maternal and infant serum concentrations were regressed on duration of breastfeeding.Results: Each month of breastfeeding was associated with lower maternal serum concentrations of PFOA (–3%; 95% CI: –5, –2%), PFOS (–3%; 95% CI: –3, –2%), PFNA (–2%; 95% CI: –2, –1%), and PFHxS (–1%; 95% CI: –2, 0%). The infant PFOA and PFOS serum concentrations were 6% (95% CI: 1, 10%) and 4% (95% CI: 1, 7%) higher per month of breastfeeding.Conclusions: Breast milk is the optimal food for infants, but is also a PFAA excretion route for lactating mothers and exposure route for nursing infants.Citation: Mondal D, Weldon RH, Armstrong BG, Gibson LJ, Lopez-Espinosa MJ, Shin HM, Fletcher T. 2014. Breastfeeding: a potential excretion route for mothers and implications for infant exposure to perfluoroalkyl acids. Environ Health Perspect 122:187–192; http://dx.doi.org/10.1289/ehp.1306613

Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study

Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine). Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.

96 Menstrual cycle characteristics in European and Inuit women exposed to perfluorinated chemicals: preliminary findings from a cross-sectional study

ObjectivesPerfluorooctanate (PFOA) and perfluorooctane sulfonate (PFOS) are ubiquitous man-made compounds. Studies suggest that they are possible hormonal disruptors, but findings are inconsistent. We examined the association between measured PFOS and...

THE ROLE OF CHOLINE DEPLETION IN PERFLUOROOCTANESULFONATE‐INDUCED HEPATIC STEATOSIS

Perfluorooctanesulfonate (PFOS) exposure has resulted in hepatic steatosis and hypolipidemia, believed to be the result of decreased production and secretion of VLDL and HDL and increased uptake of VLDL‐triglyceride. The hypothesis that PFOS produces hepatic steatosis via ionic sequestration of available choline necessary for the production of VLDL was examined. Plausibility was supported by identification of an ion‐triad between two molecules of choline and one molecule of PFOS in vitro. We fed male C57BL/6 mice either a control diet or a marginal methionine/choline‐deficient (mMCD) diet, both with and without PFOS. After a two‐week run‐in period on diets without PFOS, control or mMCD diets containing 0, 30, 60, or 120 mg K+PFOS/kg diet were fed for three weeks. There was a dose‐dependent increase in the relative liver weight in both control and mMCD fed mice. Dietary PFOS was also associated with dose‐dependent decreases in body weight, increases in hepatic triglyceride concentration, and increases in serum ALT, ALP, and bile acids, all with larger effects observed in mice fed mMCD compared to those fed the control diet. Serum and liver concentrations of PFOS were increased in a dose‐dependent manner on both diets; however, serum PFOS concentrations were higher and liver concentrations lower in mMCD‐fed mice compared to corresponding control‐fed mice. Metabolomic analysis demonstrated that PFOS caused a significant decrease in the hepatic concentration of many phosphatidylcholines in the PFOS‐fed mice compared to controls. Further, the average serum concentration of choline was reduced by dietary PFOS. These studies are the first to provide evidence that PFOS may cause hepatic steatosis through depletion of choline required for hepatic VLDL production and export.

Association of Osteoarthritis with Perfluorooctanoate and Perfluorooctane Sulfonate in NHANES 2003–2008

Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent, synthetic industrial chemicals. Perfluorinated compounds are linked to health impacts that may be relevant to osteoarthritis, cartilage repair, and inflammatory responses.Objectives: We investigated whether PFOA and PFOS exposures are associated with prevalence of osteoarthritis, and whether associations differ between men and women.Methods: We used multiple logistic regression to estimate associations between serum PFOA and PFOS concentrations and self-reported diagnosis of osteoarthritis in persons 20–84 years of age who participated in NHANES during 2003–2008. We adjusted for potential confounders including age, income, and race/ethnicity. Effects by sex were estimated using stratified models and interaction terms.Results: Those in the highest exposure quartile had higher odds of osteoarthritis compared with those in the lowest quartile [odds ratio (OR) for PFOA = 1.55; 95% CI: 0.99, 2.43; OR for PFOS = 1.77; 95% CI: 1.05, 2.96]. When stratifying by sex, we found positive associations for women, but not men. Women in the highest quartiles of PFOA and PFOS exposure had higher odds of osteoarthritis compared with those in the lowest quartiles (OR for PFOA = 1.98; 95% CI: 1.24, 3.19 and OR for PFOS = 1.73; 95% CI: 0.97, 3.10).Conclusions: Higher concentrations of serum PFOA were associated with osteoarthritis in women, but not men. PFOS was also associated with osteoarthritis in women only, though effect estimates for women were not significant. More research is needed to clarify potential differences in susceptibility between women and men with regard to possible effects of these and other endocrine-disrupting chemicals.