Concentrations Of Perfluoroundecanoic Acid Research Articles

PFDA promotes cancer metastasis through macrophage M2 polarization mediated by Wnt/β-catenin signaling

Perfluoroundecanoic acid (PFDA) is extensively utilized in the textile and food processing industries and may have a tumor-promoting effect by modulating the tumor microenvironment. Macrophages play crucial roles in tumor microenvironment as key regulators of tumor immunity. However, further investigation is needed to elucidate how PFDA interacts with macrophages and contributes to tumor progression. In this study, we treated the macrophage cell line RAW264.7 with various concentrations of PFDA and found that RAW264.7 transitioned into an M2 tumor-promoting phenotype. Through bioinformatic analysis and subsequent verification of molecular assays, we uncovered that PFDA could activate β-catenin and enhance its nuclear translocation. Additionally, it was also observed that inhibiting β-catenin nuclear translocation partly attenuated RAW264.7 M2 polarization induced by PFDA. The conditioned medium derived from PFDA-pretreated RAW264.7 cells significantly promoted the migration and invasion abilities of human ovarian cancer cells. Furthermore, in vivo studies corroborated that PFDA-pretreated RAW264.7 could promote tumor metastasis, which could be mitigated by pretreatment with the β-catenin inhibitor ICG001. In conclusion, our study demonstrated that PFDA could promote cancer metastasis through regulating macrophage M2 polarization in a Wnt/β-catenin-dependent manner.

Associations of Pregnancy Per- and Polyfluoroalkyl Substance Concentrations and Uterine Fibroid Changes across Pregnancy: NICHD Fetal Growth Studies - Singletons Cohort.

Fibroids (hormonally responsive benign tumors) often undergo volume changes in pregnancy. Because per- and polyfluoroalkyl substances (PFAS) disrupt hormonal signaling, they might affect fibroid growth. We assessed associations between PFAS and fibroid changes in pregnancy. We analyzed seven PFAS, including perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), in plasma collected at 10-13 wk gestation from 2,621 women in the NICHD Fetal Growth Studies - Singletons cohort (2009-2013). Sonographers recorded fibroid number and volume of the three largest fibroids during up to six timed ultrasounds. Generalized linear models assessed associations of baseline PFAS and fibroid number, volume, and presence, and weighted quantile sum regression evaluated the PFAS mixture. Generalized linear mixed models with random intercepts assessed associations of PFAS and longitudinal fibroid number and total volume. Volume analyses were stratified by total volume at first visualization [equivalent to a fibroid (small), (medium), or (large) in diameter]. Fibroid prevalence was 9.4% ( women). PFAS were not associated with changes in fibroid number, but were associated with volume trajectory, depending on baseline volume. Among women with small volume, PFAS were associated with fibroid growth: Each doubling in PFHxS and PFOS concentrations was associated with 3.6% [95% confidence interval (CI): 0.2, 7.0 and 5.2% (95% CI: , 11.1)] greater weekly fibroid growth, respectively. Among women with medium volume, PFAS were associated with shrinking: Doublings in PFOS, PFDA, and PFUnDA concentrations were associated with 1.9% (95% CI: 0.4, 3.3), 1.2% (95% CI: 0.1, 2.4), and 1.6% (95% CI: 0.4, 2.8) greater weekly fibroid volume reduction, respectively. Certain PFAS were associated with fibroid growth among women with small fibroids and decreases among women with medium fibroids. PFAS were not associated with fibroid prevalence or number; therefore, PFAS may influence prevalent fibroids rather than initiating fibroid development. https://doi.org/10.1289/EHP11606.

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.

Perfluoroalkyl and polyfluoroalkyl substances in cord serum of newborns and their potential factors

The demonstrated developmental and reproductive toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), coupled with the increasing production and use of emerging per- and polyfluoroalkyl substances (PFASs) has resulted in progressively higher human exposure levels. This has raised concerns about PFAS exposure levels in the fetus, which is highly susceptible to the potential effects of hazardous environmental chemicals. However, in utero exposure to PFASs and health implications have not been fully characterized in China. To fill this gap, we analyzed 19 PFASs in umbilical cord serum samples (n = 66). Information about the mothers and newborns was obtained through questionnaires. Associations between maternal characteristics and neonatal birth weight and PFAS concentrations were analyzed using nonparametric tests. As results, PFOA was detected in all serum samples. The highest median concentration of PFOS in umbilical serum was 1.092 ng·mL-1, followed by perfluoropentanoic acid (median: 0.633 ng·mL-1). Trifluroacetic acid and perfluoropropanoic acid were detected in cord serum for the first time, and their median concentrations were 0.229 and 0.266 ng·mL-1, respectively. Neonatal birth weight was negatively correlated with long-chain PFOS (r = −0.319, P < 0.05), and the concentrations of perfluoroundecanoic acid and perfluorododecanoic acid were significantly different between the birth weight groups. Maternal age, maternal education, diet, and nutritional supplementation during pregnancy can all affect umbilical serum exposure to PFASs. These results demonstrate that legacy PFASs remain major contributors to the composition of human PFASs, while the concentration levels of emerging short-chain alternatives have increased significantly. Modifying the mother's diet may reduce the risk of intrauterine PFAS exposure. Special attention to exposure to highly novel PFASs and confirmation of potential determinants should be taken as a priority in the plan for risk management and actions in this area.

Association of maternal perfluoroalkyl substance exposure with postpartum haemorrhage in Guangxi, China

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (β: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (β: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage.

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

Maternal levels of perfluoroalkyl substances (PFASs) during pregnancy and childhood allergy and asthma related outcomes and infections in the Norwegian Mother and Child (MoBa) cohort

IntroductionPrenatal exposure to perfluoroalkyl substances (PFASs) has been inconsistently associated with asthma and allergic diseases and increased number of infections in early childhood. We examined the association of PFASs measured in pregnancy with childhood asthma, allergies and common infectious diseases in a prospective pregnancy cohort followed to age 7 years. Material and methodsSix PFASs (out of 19 measured) with at least 80% of measurements above the limit of quantification (LOQ) in maternal plasma during pregnancy in two subcohorts of the Norwegian Mother and Child Cohort Study (MoBa) were analyzed in relation to health outcomes: perfluorooctane sulfonic acid (PFOS), acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluoroheptane sulfonic acid (PFHpS). Follow-up questionnaires were completed at 3 years by 1270 women and at 7 years by 972 women among the 1943 with pregnancy questionnaire and PFAS measures. Health outcomes included parent reports of child's symptoms or doctor diagnosed asthma and allergic conditions at age 7 years and parent-reported frequency of various infections at 3 and 7 years of age. Logistic and Poisson regression were used. The false discovery rate was controlled at 5%. Sensitivity analyses on gender were performed. ResultsAmong the allergy and asthma outcomes, a statistically significant inverse association was seen between PFUnDA concentrations and ever having atopic eczema in girls. PFUnDA also tended to be inversely associated with both wheeze and asthma. For infections from 0 to 3 and 6 to 7 years, 11 significant positive associations were seen between PFASs and airways infections (bronchitis/pneumonia, throat infection, pseudocroup), ear infection and gastric flu/diarrhea; whereas 6 inverse associations were seen for pseudocroup, ear infections and urinary tract infections. The majority of the findings with respect to infectious diseases were found in girls only. DiscussionWith the exception of an inverse association between PFUnDA and eczema, and a tendency of a similar association for wheeze and asthma, maternal PFAS levels during pregnancy showed little association with asthma or allergy related outcomes. Findings from the present study suggest immunosuppressive effects of PFASs on airways infections, such as bronchitis/pneumonia and throat infections, as well as diarrhea/gastric flu. Our results indicate a possible role of gender in the PFAS-health outcome associations.

Perfluoroalkyl Acids in Marine Organisms from Lake Shihwa, Korea

To our knowledge, this is the first report of concentrations of perfluorooctanesulfonate (PFOS) and other perfluoroalkyl acids (PFAs) in marine organisms from the industrialized region of Korea. Concentrations of eight PFAs were determined in three species of fish (mullet, shad, and rockfish) and three species of marine invertebrates (blue crab, oyster, and mussel) from Lake Shihwa, Korea. This is an area in which relatively great concentrations of PFAs in water and in adjacent industrial effluents have been reported. PFOS was the dominant PFA in marine organisms and most PFOS concentrations were greater than the sum of all other PFAs. The mean concentrations of PFOS were 8.1 x 10 and 3.6 x 10 ng/g, wet weight in liver and blood of fish, respectively. Perfluorocarboxylic acids (PFCAs) were also found in fish, but their concentrations were 10-fold less than those for PFOS. Of the PFCAs measured in fish, concentrations of the longer-chain perfluoroundecanoic acid (PFUnA) were the greatest. Concentrations of PFOS in soft tissues of blue crabs decreased as a function of distance from the shore where inputs from the industrialized areas are discharged into Lake Shihwa. PFOS was the only PFA detectable in mussels and oysters with a mean of 0.5 +/- 0.2 and 1.1 +/- 0.3 ng/g, wet weight, respectively. Concentrations of PFUnA were positively correlated with perfluorodecanoic acid (PFDA) in both the liver and blood of fish, which suggests a common source of these two PFCAs in this area. Hazard quotients developed for fish species were all less than 1.0 for fish collected in Lake Shihwa.

Contamination and Effects of Perfluorochemicals in Baikal Seal (Pusa sibirica). 1. Residue Level, Tissue Distribution, and Temporal Trend

Concentrations of perfluorochemicals (PFCs) including perfluoroalkylsulfonates (PFSAs) and perfluoroalkylcarboxylates (PFCAs) were determined in liver and serum of Baikal seals (Pusa sibirica) collected from Lake Baikal, Russia in 2005. Among the 10 PFC compounds measured, perfluorononanoic acid (PFNA, 3.3-72 ng/g wet wt) concentrations were the highest in liver, followed by perfluorooctanesulfonate (PFOS, 2.6-38 ng/g). The accumulation profile of long-chain (C7-C12) PFCAs in particular, the predominance of PFNA, indicated that 8:2 fluorotelomer alcohol or commercially manufactured PFNA is a major local source of PFCs in Lake Baikal. No gender-related differences in the concentrations of individual PFCs or total PFCs were found. Tissues from pups and juveniles contained relatively higher concentrations of PFCs than tissues from subadults and adults, suggesting that maternal transfer of PFCs is of critical importance. Comparison of concentrations of PFCs in livers and sera collected from the same individuals of Baikal seals revealed that residue levels of PFOS, PFNA, perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were significantly higher in liver than in serum. The concentration ratios of PFNA and PFDA between liver and serum were calculated to be 14 and 15, respectively, whereas the ratio of PFOS was 2.4. This suggests preferential retention of both PFNA and PFDA in liver. Concentrations of PFOS, PFNA, and PFDA in liver were significantly correlated with those in serum, whereas concentrations of PFUnDA were not correlated in between the two tissues, suggesting differences in pharmacokinetics among these PFCs. Temporal comparisons of hepatic PFC concentrations in seals collected between 1992 and 2005 showed that the concentrations of PFOS (p = 0.0006), PFNA (p = 0.061) and PFDA (p = 0.017) were higher in animals collected in recentyears, indicating ongoing sources of PFC contamination in Lake Baikal.

Identification of adenylate cyclase-coupled beta-adrenergic receptors with radiolabeled beta-adrenergic antagonists

The demonstrated developmental and reproductive toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), coupled with the increasing production and use of emerging per- and polyfluoroalkyl substances (PFASs) has resulted in progressively higher human exposure levels. This has raised concerns about PFAS exposure levels in the fetus, which is highly susceptible to the potential effects of hazardous environmental chemicals. However, in utero exposure to PFASs and health implications have not been fully characterized in China. To fill this gap, we analyzed 19 PFASs in umbilical cord serum samples (n = 66). Information about the mothers and newborns was obtained through questionnaires. Associations between maternal characteristics and neonatal birth weight and PFAS concentrations were analyzed using nonparametric tests. As results, PFOA was detected in all serum samples. The highest median concentration of PFOS in umbilical serum was 1.092 ng·mL-1, followed by perfluoropentanoic acid (median: 0.633 ng·mL-1). Trifluroacetic acid and perfluoropropanoic acid were detected in cord serum for the first time, and their median concentrations were 0.229 and 0.266 ng·mL-1, respectively. Neonatal birth weight was negatively correlated with long-chain PFOS (r = −0.319, P < 0.05), and the concentrations of perfluoroundecanoic acid and perfluorododecanoic acid were significantly different between the birth weight groups. Maternal age, maternal education, diet, and nutritional supplementation during pregnancy can all affect umbilical serum exposure to PFASs. These results demonstrate that legacy PFASs remain major contributors to the composition of human PFASs, while the concentration levels of emerging short-chain alternatives have increased significantly. Modifying the mother's diet may reduce the risk of intrauterine PFAS exposure. Special attention to exposure to highly novel PFASs and confirmation of potential determinants should be taken as a priority in the plan for risk management and actions in this area.