Perfluoroundecanoic Acid Research Articles

Exposure to perfluoroalkyl substances in early pregnancy and the risk of hypertensive disorders of pregnancy: A nested case-control study in Guangxi, China

BackgroundPrevious epidemiological studies have examined the associations between exposure to perfluoroalkyl substances (PFASs) and the risk of hypertensive disorders of pregnancy (HDP). However, these studies have drawn discrepant conclusions and have some limitations. MethodsA nested case-control study was conducted with the Guangxi Zhuang Birth Cohort (GZBC), a prospective, ongoing birth cohort that was implemented in Guangxi, China, in June 2015. Maternal serum concentrations of nine PFASs were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The associations between PFAS exposure and the risk of HDP were assessed using logistic regression (single-exposure), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models. ResultsA total of 136 HDP cases and 408 controls were enrolled in this study. In logistic regression models, perfluoroundecanoic acid (PFUnA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorobutanesulfonic acid (PFBS) were positively associated with HDP, while perfluorohexane sulfonate (PFHxS) was inversely associated with HDP. In the BKMR analysis, the joint effect of PFASs was positively associated with HDP. PFOS and PFBS showed positive trends, while PFHxS and PFHpA showed inverse trends. In WQS regression analysis, we calculated two WQS indices that were estimated using constraints in both the positive and negative directions of effects. Both WQS indices were significantly associated with HDP (OR: 2.663, 95% CI: 1.795–3.951; OR: 0.338, 95% CI: 0.229–0.499, respectively). PFBS, PFOS and PFUnA had significant weights in the positive effect direction; PFHxS, perfluoroheptanoic acid (PFHpA) and perfluorododecanoic acid (PFDoA) had significant weights in the negative effect direction. ConclusionConsidering all model results, we found that combined exposure to nine PFASs had a positive effect on the development of HDP. Moreover, PFOS and PFBS were positively associated with the HDP risk, while PFHxS and PFHpA were negatively associated with the HDP risk in women in Guangxi, China.

Lipidomic Analyses Reveal Modulation of Lipid Metabolism by the PFAS Perfluoroundecanoic Acid (PFUnDA) in Non-Obese Diabetic Mice.

Exposure to Per- and polyfluoroalkyl substances (PFAS) has been linked to multiple undesirable health outcomes across a full lifespan, both in animal models as well as in human epidemiological studies. Immunosuppressive effects of PFAS have been reported, including increased risk of infections and suppressed vaccination responses in early childhood, as well as association with immunotoxicity and diabetes. On a mechanistic level, PFAS exposure has been linked with metabolic disturbances, particularly in lipid metabolism, but the underlying mechanisms are poorly characterized. Herein we explore lipidomic signatures of prenatal and early-life exposure to perfluoroundecanoic acid (PFUnDA) in non-obese diabetic (NOD) mice; an experimental model of autoimmune diabetes. Female NOD mice were exposed to four levels of PFUnDA in drinking water at mating, during gestation and lactation, and during the first weeks of life of female offspring. At offspring age of 11–12 weeks, insulitis and immunological endpoints were assessed, and serum samples were collected for comprehensive lipidomic analyses. We investigated the associations between exposure, lipidomic profile, insulitis grade, number of macrophages and apoptotic, active-caspase-3-positive cells in pancreatic islets. Dose-dependent changes in lipidomic profiles in mice exposed to PFUnDA were observed, with most profound changes seen at the highest exposure levels. Overall, PFUnDA exposure caused downregulation of phospholipids and triacylglycerols containing polyunsaturated fatty acids. Our results show that PFUnDA exposure in NOD mice alters lipid metabolism and is associated with pancreatic insulitis grade. Moreover, the results are in line with those reported in human studies, thus suggesting NOD mice as a suitable model to study the impacts of environmental chemicals on T1D.

Exposure to perfluoroalkyl substances was associated with estrogen homeostasis in pregnant women

Previous studies have suggested that perfluoroalkyl substances (PFASs) can act as endocrine disruptors, but few studies have investigated the effects of serum PFASs on estrogen homeostasis during pregnancy. The present study included 557 pregnant women in Tangshan City, North China, and determined 11 serum PFASs in the early term of pregnancy and three typical estrogens (estrone (E1), estradiol (E2) and estriol (E3)) in the early (n = 557), middle (n = 339), and late (n = 286) terms of pregnancy. Sociodemographic factors and diet information were obtained by structured questionnaires. After adjusting for potential confounders, multiple linear regression model demonstrated negative associations of natural logarithmic transformed serum perfluoroundecanoic acid (Ln PFUdA) with Ln E1and Ln E3 in the early term of pregnancy with β coefficients of −0.060 (95% confidence interval (CI): −0.101 to −0.019) and -0.041 (95% CI: −0.070 to −0.011), respectively. Ln perfluorodecanoic acid (PFDA) was negatively associated with averaged E1 in the early and middle (EM) terms of pregnancy with a β coefficient of −0.205 (95% CI: −0.357 to −0.053). Ln perfluorononanoic acid (PFNA) tended to be negatively associated with E2 in the late term of pregnancy with a β coefficient of −0.134 (95% CI: −0.253 to −0.016) although p-value was slightly greater than 0.05 after false discovery rate (FDR) correction. Mixed effect model found that serum PFDA was negatively associated with E1 (β = −0.123, 95% CI: −0.235 to −0.012) during the entire pregnancy. These findings suggested that exposure to PFASs disturbed estrogen homeostasis in pregnant women and the effects varied with the terms of pregnancy.

Exposure to per and polyfluoroalkyl acids (PFAAs) from diet and lifestyle factors among Inuit adults of Nunavik, Canada

BACKGROUND AND AIM: Perfluoroalkyl acids (PFAAs) are water/stain resistant compounds resistant to metabolic degradation, making them environmentally stable, mobile and bioaccumulative. This leads to high concentrations in wildlife species essential to the cultural identity and subsistence of Arctic populations, including the Inuit. Our objective was to characterize the distribution and exposure determinants of PFAAs among the Inuit adults of Nunavik. METHODS: The study included 443 randomly selected Nunavik residents (Nunavimmiut) aged 16-82 years who participated in the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey. Associations between plasma concentrations of nine PFAAs and country food consumption, drinking water source, and traditional activity participation were examined using multiple linear regression models. RESULTS:PFAAs concentrations among Nunavimmiut were up to seven times higher than those in the general adult Canadian population. After adjustment, above-median consumption of marine mammal, fish, and game bird were associated with increased concentrations of perfluorooctanoic-acid (PFOA), perfluorononanoic-acid (PFNA), perfluorodecanoic-acid (PFDA), perfluoroundecanoic-acid (PFUndA), perfluorohexanesulfonic-acid (PFHxS), and perfluorooctanesulfonic-acid (PFOS). Of note, marine mammal consumption ≥1/week was associated with a 43.2-53.5% increase in PFNA, PFDA, PFUndA, PFHxS, and PFOS (p-values≤0.008). In addition, the omega-3 to omega-6 polyunsaturated fatty acids ratio in red blood cell membranes, indicative of marine mammal and fish consumption, was linearly associated with higher long-chain PFAAs (PFNA, PFDA, PFUdA), including a 97.3% (95% CI: 81.9-115.7%) increase in PFNA, and a 146.2% (95% CI: 118.1-181.1%) increase in PFDA, when contrasting the fourth versus the first quartile of the omega-3/omega-6 ratio. There were no associations between PFAAs and drinking water sources or traditional activities. CONCLUSIONS:The results speak to the importance of characterizing PFAAs exposure in Arctic communities for improved public health messaging on country foods and to provide evidence for actions aimed at reducing PFAAs exposure in the Arctic to protect the exceptional quality of country foods in Nunavik. KEYWORDS: pfas, Community-engaged research, Environmental disparities, Exposure assessment, Long-term exposure, Environmental epidemiology

Environmental chemicals and cross-sectional cognition among adults in the National Health and Nutrition Examination Survey

BACKGROUND AND AIM: Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not been tested for association with cognition in an environment-wide association framework. METHODS: In the US National Health and Nutrition Examination Survey (NHANES) 1999-2002 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants 60 years of age and older. Concentrations of environmental chemicals were measured in blood or urine. Chemicals with at least 50% of measures greater than the limit of detection were included (nchemicals=124, nclasses=16). We tested for differences in cognition by natural log transformed concentration of each chemical using parallel multivariable linear regression models accounting for age, sex, race/ethnicity, and educational attainment. We calculated false discovery rates (FDR). RESULTS:Participants with complete cognition/demographic measures and at least one chemical measure (n=5,670) were mean age 70.3 years, 51% female, 43.7% college educated, and 53.2% non-Hispanic White. The mean DSST score was 43.6 (18.1 standard deviation) and 24.2% were cognitively impaired (DSST28). In adjusted analyses, 75% higher lipid adjusted blood concentration of the pesticide DDT was associated with 1.4 points lower DSST score (95% Confidence interval (CI):-2.1,-0.7, FDR:0.0001). Similarly, 75% higher heptachlor concentration was associated with 0.9 points lower DSST score (95%CI:-1.6,-0.1, FDR:0.02). For metals, we observed 75% higher blood cadmium levels were associated with 0.7 points lower DSST score (95%CI:-1.1,-0.4, FDR:5*10-5) and 75% higher blood lead levels were associated with 0.6 points lower DSST score (95%CI:-0.9,-0.2, FRD:0.002). Among perfluoroalkyl substances, 75% higher urinary concentration of perfluoroundecanoic acid was associated with 0.5 points lower DSST score (95%CI:-1.0,0.07, FDR: 0.09). CONCLUSIONS:Exposure to environmental chemicals, particularly pesticides and metals, may be modifiable factors for reduced cognition among older adults. KEYWORDS: cognition, exposome, environment-wide association study, dementia

Association between gestational PFAS exposure and Children's adiposity in a diverse population

Perfluoroalkyl substances (PFAS) are widely distributed suspected obesogens that cross the placenta. However, few data are available to assess potential fetal effects of PFAS exposure on children's adiposity in diverse populations. To address the data gap, we estimated associations between gestational PFAS concentrations and childhood adiposity in a diverse mother-child cohort. We considered 6 PFAS in first trimester blood plasma, measured using ultra-high-performance liquid chromatography with tandem mass spectrometry, collected from non-smoking women with low-risk singleton pregnancies (n = 803). Body mass index (BMI), waist circumference (WC), fat mass, fat-free mass, and % body fat were ascertained in 4–8 year old children as measures of adiposity. We estimated associations of individual gestational PFAS with children's adiposity and overweight/obesity, adjusted for confounders. There were more non-Hispanic Black (31.7 %) and Hispanic (42.6 %) children with overweight/obesity, than non-Hispanic white (18.2 %) and Asian/Pacific Islander (16.4 %) children (p < 0.0001). Perfluorooctane sulfonate (PFOS; 5.3 ng/mL) and perfluorooctanoic acid (2.0 ng/mL) had the highest median concentrations in maternal blood. Among women without obesity (n = 667), greater perfluoroundecanoic acid (PFUnDA) was associated with their children having higher WC z-score (β = 0.08, 95%CI: 0.01, 0.14; p = 0.02), fat mass (β = 0.55 kg, 95%CI: 0.21, 0.90; p = 0.002), and % body fat (β = 0.01 %; 95%CI: 0.003, 0.01; p = 0.004), although the association of PFUnDA with fat mass attenuated at the highest concentrations. Among women without obesity, the associations of PFAS and their children's adiposity varied significantly by self-reported race-ethnicity, although the direction of the associations was inconsistent. In contrast, among the children of women with obesity, greater, PFOS, perfluorononanoic acid, and perfluorodecanoic acid concentrations were associated with less adiposity (n = 136). Our results suggest that specific PFAS may be developmental obesogens, and that maternal race-ethnicity may be an important modifier of the associations among women without obesity.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent. ObjectivesWe investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). MethodsThis study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach. ResultsOdds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)]. ConclusionPrenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.

Characterization of the distribution, source, and potential ecological risk of perfluorinated alkyl substances (PFASs) in the inland river basin of Longgang District, South China

Previous studies of perfluorinated alkyl substances (PFASs) in receiving water bodies of typical industrial parks under the low-carbon development mode are scarce. In the present study, 18 PFASs were analyzed in surface water and sediment samples of the inland river basin in Longgang District in 2017. The ΣPFAS concentrations in surface water (drought and rainy periods) and sediment ranged from 15.17 to 948.50 ng/L, 11.56–561.14 ng/L, and 1.07–28.94 ng/g dw, respectively. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorobutane sulfonate (PFBS) were the dominant pollutants in surface water, with maximum concentrations of 867.68 ng/L, 288.28 ng/L, and 245.09 ng/L, respectively. Meanwhile, PFOS, perfluoroundecanoic acid (PFUdA), PFBS, and perfluorodecanoic acid (PFDA) were the major PFASs in the sediment samples, with maximum concentrations of 9.83 ng/g dw, 11.86 ng/g dw, 5.30 ng/g dw, and 5.23 ng/g dw, respectively. In addition, PFOA and PFOS resulted from similar sources in sediment and surface water samples (P < 0.05). The risk quotient value (RQ) results showed that the control of PFOS in the treatment of pollutants in the inland river basin of Longgang District deserves more attention.

Assessment of regional and temporal trends in per- and polyfluoroalkyl substances using the Oriental Magpie (Pica serica) in Korea

Per- and polyfluoroalkyl substances (PFASs) are used in industrial and commercial products due to their amphiphilic properties. Birds have been utilized as biomonitoring species due to their environmental pollutant vulnerability and wide distribution. The Oriental Magpie (Pica serica) is a representative residential species inhabiting terrestrial environments. In this study, we measured PFAS concentrations in Magpie liver tissue (n = 253) collected from 12 Korean regions in 2004 and 2017. The predominant compounds were perfluorooctanesulfonic acid (PFOS; mean: 23.8 ng/g wet weight), perfluorotridecanoic acid (PFTrDA; 2.79 ng/g), and perfluoroundecanoic acid (PFUnDA: 2.11 ng/g). We observed significant correlations between Magpie PFAS measurements, indicating similar sources and bioaccumulation processes. Adult females showed significantly lower PFOS concentrations than adult males and young males and females, indicating that avian sex is a crucial physiological factor of PFAS accumulation. PFOS, perfluorodecanoic acid (PFDA), and perfluorotetradecanoic acid (PFTeDA) concentrations in urban regions were significantly higher than rural regions. PFOS concentrations in Magpie livers increased significantly between sampling years, whereas C11–C13 carboxylic acids (PFCAs) decreased. This suggests that urbanization and population are major factors in Magpie PFAS accumulation. Almost all hepatic PFOS concentrations were below the threshold values proposed by previous studies, implying limited risks. Our findings suggest that the Oriental Magpies are PFAS sentinel in residential environments. This is the first comprehensive report on biomonitoring of PFASs using the Oriental Magpie.

Temporal trends, 2000–2017, of perfluoroalkyl acid (PFAA) concentrations in serum of Swedish adolescents

Per- and polyfluoroalkyl substances (PFAS) have been extensively used as surfactants because of their high stability and good water/oil-repellent properties. PFASs, especially perfluoroalkyl acids (PFAAs), have long biological half-lives, and exposure may cause adverse health effects in humans. We assessed temporal trends of concentrations of eight PFAAs in serum of Swedish adolescents (age 16–21 years) from the general population, and estimated the stability of PFAAs and serum samples after 6 years of storage. Repeated cross-sectional sampling was performed on five occasions (covering in total 1213 individuals, 83% males) in southern Sweden between 2000 and 2017. We analyzed serum for perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) using liquid chromatography-tandem mass spectrometry. We assessed time trends using linear regression, long-term stability was assessed by reanalyzing samples collected 2013, and the comparison was done using Pearson correlation and Bland-Altman plots.PFHxS, PFOS, and PFOA decreased by 6.7% (CI: –7.0, –6.3%), 12.6% (CI: –12.9, –12.3%), and 6.5% (CI: –6.8, –6.1%) per year, respectively, and year of sampling explained 48–81% of the variation in concentrations. PFNA and PFDA seemed to increase up to 2009 and decrease thereafter. The trends were consistent after sensitivity analyses excluding women. Strong correlations of 94–97% were observed for concentrations of all compounds, except PFHxS, after storage. The observed trends closely followed the timing of manufacturers’ voluntary phase-out initiatives, and of regulatory measures governing the compounds implemented in the EU and USA. This indicates that these actions mitigated the population’s exposure to PFHxS, PFOS, and PFOA and, in recent years, to PFNA and PFDA, in southern Sweden. Furthermore, the results suggest that PFAAs remain stable in serum samples after long-term storage.

Perfluoroalkyl Substances in Plasma of Smallmouth Bass from the Chesapeake Bay Watershed.

Smallmouth bass Micropterus dolomieu is an economically important sportfish and within the Chesapeake Bay watershed has experienced a high prevalence of external lesions, infectious disease, mortality events, reproductive endocrine disruption and population declines. To date, no clear or consistent associations with contaminants measured in fish tissue or surface water have been found. Therefore, plasma samples from two sites in the Potomac River and two in the Susquehanna River drainage basins, differing in land-use characteristics, were utilized to determine if perfluoroalkyl substances were present. Four compounds, perfluorooctane sulphonic acid (PFOS), perfluoroundecanoic acid (PFUnA), perfluorodecanoic acid (PFDA) and perfluorododecanoic acid (PFDoA), were detected in every fish. Two additional compounds, perfluorooctane sulphonamide (PFOSA) and perfluorononanoic acid (PFNA), were less commonly detected at lower concentrations, depending on the site. Concentrations of PFOS (up to 574 ng/mL) were the highest detected and varied significantly among sites. No seasonal differences (spring versus fall) in plasma concentrations were observed. Concentrations of PFOS were not significantly different between the sexes. However, PFUnA and PFDoA concentrations were higher in males than females. Both agricultural and developed land-use appeared to be associated with exposure. Further research is needed to determine if these compounds could be affecting the health of smallmouth bass and identify sources.

Impact of the increasing concentrations of selected perfluoroalkyl acids on the observed concentrations of red blood cell folate among US adults aged ≥20 years.

For the first time (N = 6291), a study was undertaken to estimate associations between the concentratio ns of red blood cell folate (RBCF) and concentration of six perfluoroalkyl acids (PFAAs), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) for US adults aged ≥20 years by fitting regression models for the data from National Health and Nutrition Examination Survey for 2007-2014. In almost consistent fashion, increasing concentrations of PFAAs were associated with decreasing concentrations of RBCF. For the total population, for a 10% increase in the concentrations of PFOA, PFOS, PFDA, PFHxS, PFNA, and PFUnDA, percent decreases in RBCF concentrations were found to be 0.33%, 0.66%, 0.83%, 0.16%, 0.89%, and 0.43%, respectively. RBCF concentrations of PFAAs were found to be 1104, 1042, 100, and 936 nmol/L across the four quartiles of PFOS; 112, 1068, 1009, and 948 nmol/L across the four quartiles of PFDA; 1125, 1054, 1005, and 967 nmol/L across the four quartiles of PFNA; and 1099, 1094, 989, and 952 nmol/L across the four quartiles of PFUnDA. Perfluorinated carboxylic acids with carbon chain length > 8 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 8. Perfluorinated chemicals with a sulfonic group with carbon chain length > 6 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 6. The degree to which concentrations of RBCF decrease varied by age, gender, and race/ethnicity. Non-Hispanic blacks as compared to non-Hispanic whites and Hispanics had the lowest decreases in RBCF concentrations. Mechanisms responsible for negative associations between RBCF and PFAA concentrations are not known and will need to be researched further.

Exposure to novel and legacy per- and polyfluoroalkyl substances (PFASs) and associations with type 2 diabetes: A case-control study in East China.

Associations between per- and polyfluoroalkyl substances (PFASs) and the incidence of type 2 diabetes are controversial in epidemiological studies. In addition, limited data are available for assessing the health effects of novel PFAS alternatives. Our study evaluated the effects of PFAS exposure on type 2 diabetes by estimating the associations of PFASs in human serum with the risk of type 2 diabetes and levels of glycemic biomarkers and lipid fractions. The case-control study consisted of 304 participants from Shandong Province, East China, half of which were diagnosed with type 2 diabetes. Logistic regression showed that most PFASs were inversely associated with the risk of type 2 diabetes after adjusting for age, sex, and body mass index. However, concentrations of perfluorooctanoic acid (PFOA) in the control group were positively associated with fasting plasma glucose levels (β=0.04, 95% confidence interval (CI): 0.0003, 0.08), which may promote the development of type 2 diabetes. Furthermore, each log-unit increase in the concentrations of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESA) were associated with a total cholesterol increase (i.e., 17.49% (95% CI: 0.93%, 34.90%), 17.49% (95% CI: 4.71%, 31.83%), and 17.49% (95% CI: 4.71%, 31.83%), respectively). Positive associations were also observed between PFNA, PFUnDA, perfluorooctane sulfonate (PFOS), and 6:2 Cl-PFESA and low-density lipoprotein cholesterol. However, no associations between PFASs and hemoglobin A1c, triglycerides, or high-density lipoprotein cholesterol reached statistical significance, nor associations between PFAS mixtures and outcomes of interest. In conclusion, the significant correlations between serum PFASs and glycemic biomarkers and lipid fractions indicated that PFAS exposure may be a potential diabetogenic factor. To the best of our knowledge, this is the first study to assess the associations between novel Cl-PFESAs and type 2 diabetes, although the inverse associations observed require clarification in future studies.

Biomarkers of poly- and perfluoroalkyl substances (PFAS) in Sub-Arctic and Arctic communities in Canada.

Polyfluoroalkyl substances and perfluoroalkyl substances (PFAS) are a family of anthropogenic chemicals that are used in food packaging, waterproof clothing, and firefighting foams for their water and oil resistant properties. Though levels of some PFAS appear to be decreasing in Canada's south, environmental levels have been increasing in the Arctic due to long-range transport. However, the implications of this on human exposures in sub-Arctic and Arctic populations in Canada have yet to be established. To address this data gap, human biomonitoring research was completed in Old Crow, Yukon, and the Dehcho region, Northwest Territories. Blood samples were collected from adults residing in seven northern First Nations and were analyzed by liquid chromatography mass spectrometry. A total of nine PFAS were quantified: perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOS), perfluorohexane sulphonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA), perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluorobutane sulphonic acid (PFBS). In the Dehcho (n=124), five PFAS had a detection rate greater than 50% including PFOS, PFOA, PFHxS, PFNA, and PFDA. In addition to these PFAS, PFUdA was also detected in at least half of the samples collected in Old Crow (n=54). Generally, male participants had higher concentrations of PFAS compared to female participants, and PFAS concentrations tended to increase with age. For most PFAS, Old Crow and Dehcho levels were similar or lower to those measured in the general Canadian population (as measured through the Canadian Health Measures Survey or CHMS) and other First Nations populations in Canada (as measured through the First Nations Biomonitoring Initiative or FNBI). The key exception to this was for PFNA which, relative to the CHMS (0.51μg/L), was approximately 1.8 times higher in Old Crow (0.94μg/L) and 2.8 times higher in Dehcho (1.42μg/L) than observed in the general Canadian population. This project provides baseline PFAS levels for participating communities, improving understanding of human exposures to PFAS in Canada. Future research should investigate site-specific PFNA exposure sources and monitor temporal trends in these regions.

Time Trend of Persistent Organic Pollutants and Metals in Greenlandic Inuit during 1994-2015.

Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs), organchlorine pesticides and perfluoroalkylated substances (PFASs) and heavy metals bioaccumulate in the marine food chain in the Arctic regions, and thus, the Greenlandic population has a higher body burden due to relatively high intake of marine mammals. We assessed the temporal trend for POPs, including PCB 153; 1,1-dichloro−2,2-bis (p-chlorophenyl)-ethylene (p,p’-DDE); oxychlordane; six PFASs; mercury; lead and selenium in Inuit from Ilulissat, Nuuk, and across Greenland (including thirteen towns/districts), from 1994 to 2015. Data showed a significant annual decrease of 6.85–8.61% for PCB153, 6.67–8.61% for p,p’-DDE, 6.11–9.52% for oxychlordane, 5.92–6.76% for mercury and 6.48–9.43% for lead in Inuit women from Nuuk, Ilulissat, and across thirteen Greenlandic districts. The blood selenium level of all Greenlandic women increased 1.01% annually, while the trend direction was negative for Nuuk women. A similar pattern was seen for men across Greenland, with a yearly decrease of 11.3% for PCB 153, 8.61% for p,p’-DDE, 15.6% for oxychlordane, 13.1% for mercury and 12.2% for lead. Perfluorooctane sulfonate, perfluorohexane sulfonate and perfluorooctanoic acid significantly decreased 5.82–11.7% annually for both women and men across Greenland. For perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid, we observed an increasing trend for women across Greenland. In conclusion, there was a decreasing trend of the regulated POPs and metals but a potential increasing trend of the nonregulated PFASs in the Greenlandic population between 1994 and 2015. The continuing biomonitoring of contaminants of concern is important to protect the Arctic population heath.

Occurrence of perfluorinated carboxylic acids in Mexico City's wastewater: A monitoring study in the sewerage and a mega wastewater treatment plant

An analytical method based on liquid chromatography coupled to mass spectrometry was validated to quantify five perfluorinated carboxylic acids (PFCA) namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), and perfluoroundecanoic acid (PFUnA), in wastewater produced in a megacity. Sampling was performed on a monthly basis, obtaining samples from the undergrounded sewerage system and the main open-air canal transporting wastewater out the city. Steady levels of the sum of the target PFCA (ƩPFCA) were determined on both sites through the study: 419.4 ± 24.3 ng L−1 in undergrounded sewage and 591.1 ± 39 ng L−1 in the open-air canal. Short-chain PFCA (PFBA, PFHxA, and PFHpA) were abundant, while concentrations of PFOA and PFUnA remained lower in both sampling sites. The open-air canal was transected in four sampling points, which were sampled throughout the monitoring campaign, finding that furtive discharges of municipal and industrial wastewater increased the levels of short-chain PFCA, while those of PFOA and PFUnA were depleted. Relevant concentrations of PFBA (176.9 ± 3.3 ng L−1), PFHxA (133.4 ± 2.5 ng L−1), PFHpA (116.6 ± 3.9 ng L−1), PFOA (133.1 ± 3.5 ng L−1), and PFUnA (23.5 ± 6.5 ng L−1) were found 60 km downstream, where the wastewater transported by the open-air canal is used in irrigation. A fraction of sewage is treated in a conventional wastewater treatment plant. The concentration of short-chain PFCA increased in effluent, adding extra loads of PFBA, PFHxA, and PFHpA to the environment.

Perfluoroundecanoic acid inhibits Leydig cell development in pubertal male rats via inducing oxidative stress and autophagy

Perfluoroundecanoic acid (PFUnA) is one of long-chain perfluoroalkyl carboxylic acids. However, the effect of PFUnA on pubertal development of Leydig cells remains unclear. The goal of this study was to investigate the effect of PFUnA on Leydig cell development in pubertal male rats. We orally dosed male Sprague-Dawley rats (age 35 days) with PFUnA at doses of 0, 1, 5, and 10 mg/kg/day from postnatal day (PND) 35 to PND 56. Serum testosterone and luteinizing hormone levels were remarkably reduced by PFUnA at ≥1 mg/kg while serum follicle-stimulating hormone levels were lowered at 5 and 10 mg/kg. PFUnA down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Hsd11b1, Insl3, Nr5a1, Fshr, Dhh, Sod1, and Sod2 and their proteins in the testis and the expression of Lhb and Fshb in the pituitary. PFUnA reduced Leydig cell number at 5 and 10 mg/kg. PFUnA induced oxidative stress and increased autophagy. These may result from the inhibition of phosphorylation of mTOR, AKT1, AKT2, and ERK1/2 in the testis. In conclusion, PFUnA exhibits inhibitory effects on pubertal Leydig cell development possibly via inducing oxidative stress and increasing autophagy.

Associations between concentrations of selected perfluoroalkyl acids and concentrations of blood cadmium, lead, and total mercury.

Data (N = 2552) from National Health and Nutrition Examination Survey for US adults aged ≥ 20 years for 2011-2016 were analyzed to estimate the associations between the concentrations of blood cadmium, lead, and total mercury and the concentrations of seven perfluoroalkyl acids (PFAA), namely, 2-(N-Methyl-perfluorooctane sulfonamido) acetic acid (MPAH), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS). Concentrations of blood cadmium were negatively associated with the concentrations of PFHxS (β = - 0.05428, p < 0.01) and PFOS (β = - 0.0212, p = 0.02). Concentrations of blood lead were positively associated with the concentrations of MPAH (β = 0.03301, p < 0.01), PFOA (β = 0.04783, p = 0.01), PFNA (β = 0.11761, p < 0.01), PFDA (β = 0.08007, p < 0.01), PFUA (β = 0.11382, p < 0.01), and PFOS (β = 0.04996, p = 0.02). Percent increases in the concentration of blood lead were 0.32%, 0.46%, 1.13%, 0.77%, 1.09%, and 0.48% for 10% increases in the concentrations of MPAH, PFOA, PFNA, PFDA, PFUA, and PFOS, respectively. Concentrations of blood total mercury were positively associated with the concentrations of PFNA (β = 0.37105, p < 0.01), PFDA (β = 0.46875, p < 0.01), PFUA (β = 0.56934, p < 0.01), and PFOS (β = 0.17557, p < 0.01). Percent increases in the concentration of blood total mercury were 3.6%, 4.57%, 5.58%, and 1.69% for 10% increases in the concentrations of PFNA, PFDA, PFUA, and PFOS, respectively. Associations between the concentrations of PFAAs with blood total mercury were substantially stronger than the concentrations with blood lead. Higher the carbon chain length for PFAAs, stronger were the associations between PFAAs with lead and mercury.

The occurrence of PFAS in human placenta and their binding abilities to human serum albumin and organic anion transporter 4.

Both legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been found to be threats to human health. In particular, fetuses are sensitive to xenobiotics and the placenta functions as a significant barrier for environmental pollutants. The placental transfer of PFAS is closely related to their interactions with proteins. In this study, 54 human placental samples were collected to investigate the occurrence of legacy and emerging PFAS in human placenta, including perfluorinated carboxylates (PFCAs), perfluorinated sulfonates (PFSAs), chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs), and fluorotelomer sulfonates (FTSAs). Among the legacy PFAS, perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in all samples, with PFOS and PFOA being the two predominant (mean: 0.457 and 0.242ng/g wet weight, respectively). Among the emerging PFAS, 6:2 Cl-PFESA was detected in all samples with the mean value of 0.104ng/g wet weight, while the detect frequency (DF) of 8:2 Cl-PFESAs was only 24%. The concentration and DF of the four FTSA congeners were low in the placentas. Molecular docking calculation results showed that the binding affinities of PFAS to the human serum albumin (HSA) were increased with chain length in each category except for the PFCAs, of which the perfluoroundecanoic acid (PFUnDA) was the turning point of binding affinity to HSA. For PFSAs, their binding affinities to organic anion transporter 4 (OAT4) were increased with the chain length except for the sodium perfluoro-1-heptanesulfonate (PFHpS) and sodium perfluoro-1-nonanesulfonate (PFNS). The calculation results demonstrated that the placental transfer of PFAS is closely related to chain length. The findings in the study can help better understand the occurrence of the PFAS in the human placenta and the placental transfer mechanisms of PFAS in human beings.

Analysis of PFAS Levels and Associations with Adolescent Anthropometric Outcomes in NHANES

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are found in some consumer products due to their heat resistance and durability. However, there is potential for these substances to bioaccumulate in humans. It is relevant to investigate biological effects of these chemicals, as studies have suggested early life exposure may impact human developmental outcomes such as infant birth weight and youth adiposity. The objective of the current study was to determine if a relationship exists between increasing levels of certain PFAS and anthropometrics in adolescents ages 12 - 18. The three PFAS examined were: perfluorodecanoic acid (PFDeA), 2-(N-methyl-perfluoroctane sulfonamido) acetic acid (Me-PFOSA-AcOH), and perfluoroundecanoic acid (PFUA). The data was obtained from the National Health and Nutrition Examination Survey (NHANES) from the years 2011-2012 (N = 287) and 2013-2014 (N = 344). An additional analysis combined data from 3 NHANES survey cycles using sampling weights for the years 2011-2016 (N = 875) to generate a larger sample size of detectable PFAS. PFAS concentrations were classified as above or below the lower limit of detection (LLOD) to evaluate differences in weight, waist circumference, BMI (body mass index), and height using Student’s t-tests. These same anthropometric outcomes were examined as continuous variables in linear regression models and were stratified by sex. In the 2013-2014 dataset, there were significant inverse associations between female concentrations of PFUA and PFDeA with waist circumference (PFUA β = −0.056; 95% CI, −0.106, −0.005; PFDeA β = −0.06; 95% CI, −0.10, −0.02), weight-for-age z-score (PFUA β = −0.40; 95% CI, −0.74, −0.05; PFDeA β = −0.38; 95% CI, −0.64, −0.12), and BMI-for-age z-score (PFUA β = −0.48; 95% CI, −0.86, −0.10; PFDeA β = −0.45; 95% CI, −0.73, −0.16). In the 2011-2012 dataset, males displayed a significant inverse relationship between PFDeA and waist circumference (β = −0.08; 95% CI, −0.14, −0.02), weight-for-age z-score (β = −0.49; 95% CI, −0.88, −0.11), and BMI-for-age z-score (β = −0.44; 95% CI, −0.84, −0.05). In the combined analysis of NHANES years 2011-2016, there were significant inverse associations with PFUA and PFDeA and weight-for-age z-score, waist circumference, and BMI-for-age z-score. In the given sample years, there was no compelling evidence for a relationship between any of the perfluoroalkyl chemicals and height, nor between Me-PFOSA-AcOH and any of the body measures after adjusting for age, sex, and race/ethnicity. This suggests that PFUA and PFDeA exposure in adolescents may be related to smaller waist circumference, weight, and BMI, but longitudinal studies are recommended to confirm these findings.