Aerobic biotransformation of 6:2 fluorotelomer sulfonate in soils from two aqueous film-forming foam (AFFF)-impacted sites.

Although 6:2 fluorotelomer sulfonate (6:2 FTS) is a common ingredient in aqueous film-forming foam (AFFF) formulations, its environmental fate at AFFF-impacted sites remains poorly understood. This study investigated the biotransformation of 6:2 FTS in microcosms prepared with soils collected from two AFFF-impacted sites; the former Loring Air Force Base (AFB) and Robins AFB. The half-life of 6:2 FTS in Loring soil was 43.3 days; while >60 mol% of initially spiked 6:2 FTS remained in Robins soil microcosms after a 224-day incubation. Differences in initial sulfate concentrations and the depletion of sulfate over the incubation likely contributed to the different 6:2 FTS biotransformation rates between the two soils. At day 224, stable transformation products, i.e., C4C7 perfluoroalkyl carboxylates, were formed with combined molar yields of 13.8 mol% and 1.2 mol% in Loring and Robins soils, respectively. Based on all detected transformation products, the biotransformation pathways of 6:2 FTS in the two soils were proposed. Microbial community analysis suggests that Desulfobacterota microorganisms may promote 6:2 FTS biotransformation via more efficient desulfonation. In addition, species from the genus Sphingomonas, which exhibited higher tolerance to elevated concentrations of 6:2 FTS and its biotransformation products, are likely to have contributed to 6:2 FTS biotransformation. This study demonstrates the potential role of biotransformation processes on the fate of 6:2 FTS at AFFF-impacted sites and highlights the need to characterize site biogeochemical properties for improved assessment of 6:2 FTS biotransformation behavior.

6:2 Chlorinated Polyfluoroalkyl Ether Sulfonates Exert Stronger Thyroid Homeostasis Disruptive Effects in Newborns than Perfluorooctanesulfonate: Evidence Based on Bayesian Benchmark Dose Values from a Population Study.

Growing toxicologic evidence suggests that emerging perfluoroalkyl substances (PFASs), like chlorinated polyfluoroalkyl ether sulfonate (Cl-PFESA), may be as toxic or more toxic than perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA). However, further investigations are needed in terms of the human health risk assessment. This study examined the effects of emerging and legacy PFAS exposure on newborn thyroid homeostasis and compared the thyroid disruption caused by 6:2 Cl-PFESA and PFOS using a benchmark dose approach. The health effects of mixture and individual exposure were estimated using the partial least-squares (PLS) model and linear regression, respectively. A Bayesian benchmark dose (BMD) analysis determined the BMD value for adverse effect comparison between 6:2 Cl-PFESA and PFOS. The median (interquartile range) concentrations of 6:2 Cl-PFESA (0.573 [0.351-0.872] ng/mL), PFOS (0.674 [0.462-1.007] ng/mL), and PFOA (1.457 [1.034, 2.405] ng/mL) were found to be similar. The PLS model ranked the PFAS variables' importance in projection (VIP) scores as follows: 6:2 Cl-PFESA > PFOS > PFOA. Linear regression showed that 6:2 Cl-PFESA had a positive association with free triiodothyronine (FT3, P = 0.006) and triiodothyronine (T3, P = 0.014), while PFOS had a marginally significant positive association with FT3 alone (P = 0.042). The BMD analysis indicated that the estimated BMD10 for 6:2 Cl-PFESA (1.01 ng/mL) was lower than that for PFOS (1.66 ng/mL) in relation to a 10% increase in FT3. These findings suggest that 6:2 Cl-PFESA, an alternative to PFOS, has a more pronounced impact on newborns' thyroid homeostasis compared to PFOS and other legacy PFASs.

Target and non-target analysis of per- and polyfluoroalkyl substances in representative chrome mist suppressants on the Chinese market.

Fluorinated chrome mist suppressants (CMSs) have been widely used in the electroplating industry globally, including China. In compliance with the Stockholm Convention on Persistent Organic Pollutants, China has phased out perfluorooctane sulfonate (PFOS) as CMS, except for closed-loop systems, before March 2019. Since then, several alternatives have been introduced to replace PFOS, but many of them still belong to the per- and polyfluoroalkyl substances (PFASs) family. In this study, for the first time, we collected and analyzed CMS samples from the Chinese market in 2013, 2015, and 2021 to determine their PFAS composition. For products with relatively few PFAS targets, we performed a total fluorine (TF) screening test and suspect and non-target analysis. Our findings suggest that 6:2 fluorotelomer sulfonate (6:2 FTS) has become the primary alternative on the Chinese market. Surprisingly, we identified 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFAES) as the primary ingredient in a CMS product (F-115B), which is the longer chain modification of the classical CMS product (F-53B). Furthermore, we identified three novel PFASs as PFOS alternatives, including hydrogen-substituted perfluoroalkyl sulfonates (H-PFSAs) and perfluorinated ether sulfonates (O-PFSAs). We also screened and identified six hydrocarbon surfactants in PFAS-free products as the primary ingredients. Despite this, some PFOS-based CMSs remain on the Chinese market. To prevent the opportunistic use of PFOS for illegal purposes, it is essential to enforce regulations strictly and ensure that such CMSs are used only in closed-loop chrome plating systems.

Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined. OBJECTIVES: This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture. METHODS: From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners. RESULTS: After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, 1m-PFOS, Σ3,4,5m-PFOS), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [adjusted odds ratio (aOR)=1.20 (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women. CONCLUSIONS: In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.

Behavioral outcomes and exposure to perfluoroalkyl substances among children aged 6-13 years: The TEDDY child study.

BACKGROUND: Although some studies report that exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy and early life stages of a child could adversely impact neurodevelopment, literature shows mixed evidence. OBJECTIVES: Using an ecological framework for human development, we assessed the association of risk factors for environmental PFAS exposure and childhood PFAS concentrations with behavioral difficulties among school-age children exposed to PFAS from birth, while also controlling for the important influence of the parenting and familial environment. METHODS: The study participants included 331 school-age children (6-13 years) born in a PFAS-contaminated area in the Veneto Region (Italy). We study the associations between environmental risk factors of maternal PFAS exposure (residential time, consumption of tap water, residence in Red zone A or B), and breastfeeding duration with parent assessments of children's behavioral problems (using the Strengths and Difficulties Questionnaire [SDQ]), adjusting for socio-demographic, parenting and familial variables. The direct relationships between serum blood PFAS concentrations and SDQ scores was evaluated in a subset of children (n = 79), both with single PFAS and weighted quantile sum (WQS) regressions. RESULTS: Poisson regression models reported positive associations between high consumption of tap water and externalizing SDQ scores (Incidence Rate Ratio [IRR]: 1.18; 95% confidence interval [CI]: 1.04-1.32) and total difficulty scores (IRR: 1.14; 95% CI: 1.02-1.26). Childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with higher internalizing SDQ scores (4th vs. 1st quartile, PFOS IRR: 1.54, 95% CI: 1.06-2.25), externalizing scores (4th vs. 1st quartile, PFHxS IRR: 1.59, 95% CI: 1.09-2.32), and total difficulty scores (4th vs. 1st quartile, PFOS IRR: 1.37, 95% CI: 1.05-1.71; PFHxS IRR: 1.54, 95% CI: 1.09-1.90). The WQS regressions confirmed the associations reported by single-PFAS analyses. CONCLUSIONS: We observed cross-sectional associations of tap water consumption and childhood PFOS, and PFHxS concentrations with greater behavioral difficulties.

Impact Mechanisms of Humic Acid on the Transmembrane Transport of Per- and Polyfluoroalkyl Substances in Wheat at the Subcellular Level: The Important Role of Slow-Type Anion Channels.

Per- and polyfluoroalkyl substances (PFASs) have potential to accumulate in crops and pose health risks to humans, but it is unclear how the widely present organic matters in soil, such as humic acid (HA), affect their uptake and translocation in plants. In this study, hydroponic experiments were conducted to systematically disclose the impacts of HA on the uptake, translocation, and transmembrane transport at the subcellular level of four PFASs, including perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorohexane sulfonic acid, and 6:2 chlorinated polyfluoroalkyl ether sulfonate in wheat (Triticum aestivum L.). The results of the uptake and depuration experiments indicated that HA depressed the adsorption and absorption of PFASs in wheat roots by reducing the bioavailability of PFASs, and HA did not affect the long-range transport of PFASs to be eliminated via the phloem of wheat. However, HA facilitated their transmembrane transport in wheat roots, while the contrary effect was observed in the shoots. The inhibitor experiments coupled with transcriptomics analysis uncover that the increased transmembrane transport of PFASs stimulated by HA is mainly driven by the slow-type anion channel pathways interacting with Ca2+-dependent protein kinases (Ca2+-CDPK-SLAC1). The promoted transmembrane transport of PFASs might cause adverse effects on the plant cell wall, which causes further concerns.

[Correlation analysis between prenatal exposure of per-/polyfluoroalkyl compounds and neonatal outcome].

Objective: To investigate the correlation between the prenatal exposure of per-/polyfluoroalkyl substances (PFASs) and the neonatal outcome. Methods: A total of 506 maternal infant cohort samples were collected in Hangzhou, Zhejiang province from 2020 to 2021. The exposure levels of seven PFASs in maternal serum before delivery were detected by solid-phase extraction-ultra performance liquid chromatography tandem mass spectrometry. Multivariable linear regression model was used to analyze the influence of prenatal exposure of PFASs on birth weight, birth length and Apgar score. Results: The maternal age, prenatal body mass index and gestation age were (31.3±4.3) years old, (26.7±3.2) kg/m2 and (265.0±28.3) days, respectively. The birth weight, birth length and scores of Apgar-1 and Apgar-5 were (3.1±0.8) kg, (49.3±2.9) cm, (9.88±0.47) points and (9.99±0.13) points, respectively. PFASs were widely distributed in maternal serum, with the highest concentration of (18.453±19.557) ng/ml, (6.756±9.379) ng/ml and (5.057±8.555) ng/ml for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and 6∶2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), respectively. Maternal age, parity and delivery mode were associated with the exposure level of PFASs (P<0.05). Subgroup analysis showed that PFOS had negative effects on birth weight (ß=-0.958), birth length (ß=-0.073) and Apgar-5 score (ß=-0.288) for neonates in the low birth weight (LBW) group. 6∶2 Cl-PFESA and 8∶2 Cl-PFESA inhibited the birth weight (ß=-0.926; ß=-0.552) and length (ß=-0.074; ß=-0.045) of newborn in the LBW group. In addition, 4∶2 fluorotelomer sulfonate (FTS) was associated with increased birth weight (ß=0.111) and decreased Apgar-5 score (ß=-0.030) in the normal weight group. Conclusion: Prenatal exposure to PFASs is associated with birth weight, birth length and Apgar-5 score. It is necessary to continue to pay attention to the impact of PFASs on fetal growth and development through maternal-fetal transmission.

Perfluorinated compound correlation between human serum and drinking water: Is drinking water a significant contributor?

Perfluorinated compounds (PFASs) are a new artificial chemical. Due to its substantial toxicity and complex degradation in the natural environment, monitoring PFASs has become a hot issue for many researchers. Currently, the relationship between the concentration of PFASs in serum and the concentration of PFASs in drinking water is unclear. This paper aims to study the concentration levels of PFASs in drinking water and residents' serum in a city in northern China and the relationship between them. The results show that the concentration of PFASs in drinking water is low, and the average concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were 2.57 ± 0.69 ng/L and 0.30 ng/L, respectively, which were lower than the limits specified in China's newly introduced Standards for drinking water quality (GB 5749-2022). In the serum of residents, PFOA and PFOS were the two PFASs with the highest concentration. Spearman correlation analysis showed that perfluorohexane sulfonate (PFHxS) and PFOS concentrations were positively correlated with age, and PFHxS, PFOA, PFNA, and PFOS varied with sex. At the same time, the correlation analysis also showed no correlation between PFAS in drinking water and serum, indicating that drinking water was not the main factor causing the physical burden of PFAS in residents. The HI method was used to assess the health risks of PFASs to human beings. The risk entropy of all PFASs for human hepatotoxicity and reproductive toxicity is below 1.

Spatio-temporal trends in livestock exposure to per- and polyfluoroalkyl substances (PFAS) inform risk assessment and management measures.

The migration of per- and polyfluoroalkyl substances (PFAS) onto agricultural properties has resulted in the accumulation of PFAS in livestock. The environmental determinants of PFAS accumulation in livestock from the grazing environment are poorly understood, resulting in limited capacity to manage livestock exposure and subsequent transfer of PFAS through the food chain. Analytical- (n = 978 samples of soil, water, pasture, and serum matrices), farm management/practice- and livestock physiology data were collated and interrogated from environmental PFAS investigations across ten farms, from four agro-ecological regions of Victoria (Australia). Statistical analysis identified perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) as key analytes of concern for livestock bioaccumulation. PFOS and PFHxS concentrations in livestock drinking water were positively correlated with serum concentrations while other intake pathways (pasture and soil) had weaker correlations. Seasonal trends in PFAS body burden (serum concentrations) were identified and suggested to be linked to seasonal grazing behaviours and physiological water requirements. The data showed for the first time that livestock exposure to PFAS is dynamic and with relatively short elimination half-lives, there is opportunity for exposure management. Meat from cattle, grazed on PFAS impacted sites, may exceed health-based guideline values for PFAS, especially for markets with low limits (like the European Commission Maximum Limits or EC MLs). This study found that sites with mean livestock drinking water concentrations as low as 0.003 µg PFOS/L may exceed the EC ML for PFOS in cattle meat. Risk assessment can be used to prioritise site cleanup and development of management plans to reduce PFAS body burden by considering timing of stock rotation and/or supplementation of primary exposure sources.

Joint effects of per- and polyfluoroalkyl substance alternatives and heavy metals on renal health: A community-based population study in China.

BACKGROUND: Previous studies have indicated that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), when used as an alternative to per- and polyfluoroalkyl substances (PFASs), result in kidney toxicity. However, their co-exposure with heavy metals, has not yet been described. OBJECTIVES: To explore the joint effects of Cl-PFESAs and heavy metal exposure on renal health in Chinese adults, and identify specific pollutants driving the associations. METHODS: Our sample consists of 1312 adults from a cross-sectional survey of general communities in Guangzhou, China. We measured Cl-PFESAs, legacy PFASs (perfluorooctanoic acid [PFOA] and perfluorooctane sulfonated [PFOS]), and heavy metals (arsenic, cadmium, and lead). The relationship between single pollutant and glomerular filtration rate (eGFR) and the odds ratio (OR) of chronic kidney disease (CKD) was studied using Generalized additive models (GAMs). Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint effects of Cl-PFESAs and heavy metals. Additionally, we conducted a sex-specific analysis to determine the modification effect of this variable. RESULTS: In single pollutant models, CI-PFESAs, PFOA, PFOS and arsenic were negatively associated with eGFR. Additionally, PFOA and heavy metals were positively correlated with the OR of CKD. For example, the estimated change with 95% confidence intervals (CI) of eGFR at from the highest quantile of 6:2 Cl-PFESA versus the lowest quantile was -5.65 ng/mL (95% CI: -8.21, -3.10). Sex played a role in modifying the association between 8:2 Cl-PFESA, PFOS and eGFR. In BKMR models, pollutant mixtures had a negative joint association with eGFR and a positive joint effect on CKD, especially in women. Arsenic appeared to be the primary contributing pollutant. CONCLUSION: We provide epidemiological evidence that Cl-PFESAs independently and jointly with heavy metals impaired kidney health. More population-based human and animal studies are needed to confirm our results.

Correlation analysis between prenatal exposure of per-/polyfluoroalkyl compounds and neonatal outcome / 中华预防医学杂志

Objective: To investigate the correlation between the prenatal exposure of per-/polyfluoroalkyl substances (PFASs) and the neonatal outcome. Methods: A total of 506 maternal infant cohort samples were collected in Hangzhou, Zhejiang province from 2020 to 2021. The exposure levels of seven PFASs in maternal serum before delivery were detected by solid-phase extraction-ultra performance liquid chromatography tandem mass spectrometry. Multivariable linear regression model was used to analyze the influence of prenatal exposure of PFASs on birth weight, birth length and Apgar score. Results: The maternal age, prenatal body mass index and gestation age were (31.3±4.3) years old, (26.7±3.2) kg/m2 and (265.0±28.3) days, respectively. The birth weight, birth length and scores of Apgar-1 and Apgar-5 were (3.1±0.8) kg, (49.3±2.9) cm, (9.88±0.47) points and (9.99±0.13) points, respectively. PFASs were widely distributed in maternal serum, with the highest concentration of (18.453±19.557) ng/ml, (6.756±9.379) ng/ml and (5.057±8.555) ng/ml for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and 6∶2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), respectively. Maternal age, parity and delivery mode were associated with the exposure level of PFASs (P<0.05). Subgroup analysis showed that PFOS had negative effects on birth weight (β=-0.958), birth length (β=-0.073) and Apgar-5 score (β=-0.288) for neonates in the low birth weight (LBW) group. 6∶2 Cl-PFESA and 8∶2 Cl-PFESA inhibited the birth weight (β=-0.926; β=-0.552) and length (β=-0.074; β=-0.045) of newborn in the LBW group. In addition, 4∶2 fluorotelomer sulfonate (FTS) was associated with increased birth weight (β=0.111) and decreased Apgar-5 score (β=-0.030) in the normal weight group. Conclusion: Prenatal exposure to PFASs is associated with birth weight, birth length and Apgar-5 score. It is necessary to continue to pay attention to the impact of PFASs on fetal growth and development through maternal-fetal transmission.

Environmentally relevant concentrations of F-53B induce eye development disorders-mediated locomotor behavior in zebrafish larvae.

The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 µg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis.

Bioaccumulation and trophic magnification of emerging and legacy per- and polyfluoroalkyl substances (PFAS) in a St. Lawrence River food web.

Research on per- and polyfluoroalkyl substances (PFAS) in freshwater ecosystems has focused primarily on legacy compounds and little is still known on the presence of emerging PFAS. Here, we investigated the occurrence of 60 anionic, zwitterionic, and cationic PFAS in a food web of the St. Lawrence River (Quebec, Canada) near a major metropolitan area. Water, sediments, aquatic vegetation, invertebrates, and 14 fish species were targeted for analysis. Levels of perfluorobutanoic acid (PFBA) in river water exceeded those of perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS), and a zwitterionic betaine was observed for the first time in the St. Lawrence River. The highest mean PFAS concentrations were observed for the benthopelagic top predator Smallmouth bass (Micropterus dolomieu, Σ60PFAS âˆ¼ 92 ± 34 ng/g wet weight whole-body) and the lowest for aquatic plants (0.52-2.3 ng/g). Up to 33 PFAS were detected in biotic samples, with frequent occurrences of emerging PFAS such as perfluorobutane sulfonamide (FBSA) and perfluoroethyl cyclohexane sulfonate (PFECHS), while targeted ether-PFAS all remained undetected. PFOS and long-chain perfluorocarboxylates (C10-C13 PFCAs) dominated the contamination profiles in biota except for insects where PFBA was predominant. Gammarids, molluscs, and insects also had frequent detections of PFOA and fluorotelomer sulfonates, an important distinction with fish and presumably due to different metabolism. Based on bioaccumulation factors >5000 and trophic magnification factors >1, long-chain (C10-C13) PFCAs, PFOS, perfluorodecane sulfonate, and perfluorooctane sulfonamide qualified as very bioaccumulative and biomagnifying. Newly monitored PFAS such as FBSA and PFECHS were biomagnified but moderately bioaccumulative, while PFOA was biodiluted.

Exposure to per- and polyfluoroalkyl substances as a risk factor for gestational diabetes mellitus through interference with glucose homeostasis.

Per- and polyfluoroalkyl substances (PFASs) are hypothesized to trigger gestational diabetes mellitus (GDM) through modulation of glucose metabolism. However, studies investigating links between joint PFASs to GDM are limited and led to discrepant conclusions. This study included 171 women with GDM development in pregnancy and 169 healthy controls from Hangzhou, China between October 2020 and September 2021. By using the solid-phase extraction (SPE)-ultra performance liquid chromatography-tandem-mass-spectrometry (UPLC/MS-MS), 15 PFASs were detected to be widely distributed in maternal serum, with highest median concentrations of 7.43, 4.23, and 3.64 ng/mL for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonates (6:2 Cl-PFESA). Multivariable logistic regressions suggested that the adjusted odds ratios (ORs) with 95% confidence intervals (CI) of GDM for second and highest tertiles of PFOA were 2.57 (1.24, 4.86), p = 0.001 and 1.98 (1.06, 3.65), p = 0.023. Compared with the reference tertile, the ORs of GDM were also significantly increased at the highest tertile of perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoA), PFOS and 6:2Cl-PFESA. Multiple linear regressions further indicated that exposure to these PFASs congeners were positively associated with continuous glycemic outcomes of fasting blood glucose (FBG), 1-h, and 2-h glucose after 75 g oral glucose tolerance (OGTT) test as well as glycohemoglobin (HbA1c). Nevertheless, perfluorohexane sulfonic acid (PFHxS), 4:2 fluorotelomer sulfonates (FTSs), and 3H-perfluoro-3-[(3-methoxy-propoxy) propanoic acid] (ADONA) exhibited protective effects on some of these glycemic outcomes. When assessing the PFASs as mixtures by conducting the Bayesian kernel machine regression (BKMR), the risks of GDM and values of glycemic outcomes increased significantly as the concentrations of the PFASs mixture increased, with PFOA being the largest contributor. We therefore propose that although the effects on glucose homeostasis varied between different PFAS congeners, the elevated combined exposures to PFASs may be associated with substantially increased GDM risks by altering glucose metabolism.

Tissue-Specific Uptake, Depuration Kinetics, and Suspected Metabolites of Three Emerging Per- and Polyfluoroalkyl Substances (PFASs) in Marine Medaka.

Restrictions on legacy per- and polyfluoroalkyl substances (PFASs) have led to the widespread use of emerging PFASs. However, their toxicokinetics have rarely been reported. Here, tissue-specific uptake and depuration kinetics of perfluoroethylcyclohexanesulfonate (PFECHS) and 6:2 and 8:2 chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs) were studied in marine medaka (Oryzias melastigma). The fish were exposed to these substances for 28 days (0.2 µg/L), followed by a clearance period of 14 days. The depuration constant (kd) of PFECHS [0.103 ± 0.009 day-1 (mean ± standard deviation)] was reported for the first time. Among the six studied tissues, the highest concentrations of 6:2 Cl-PFESA, 8:2 Cl-PFESA, and PFECHS were found in the liver [1540, 1230, and 188 ng (g of wet weight)-1, respectively] on day 28 while the longest residence times were found in the eyes (t1/2 values of 21.7 ± 4.3, 23.9 ± 1.5, and 17.3 ± 0.8 days, respectively). No significant positive correlation was found between the bioconcentration factors of the studied PFASs and the phospholipid or protein contents in different tissues of the studied fish. Potential metabolites of Cl-PFESAs, i.e., their hydrogen-substituted analogues (H-PFESAs), were identified by time-of-flight mass spectrometry. However, the biotransformation rates were low (<0.19%), indicating the poor capacity of marine medaka to metabolize Cl-PFESAs to H-PFESAs.

Environmental exposure to legacy poly/perfluoroalkyl substances, emerging alternatives and isomers and semen quality in men: A mixture analysis.

BACKGROUND/OBJECTIVES: Multiple studies have examined the relationship between PFAS and semen quality, but none has explored the associations of PFAS mixture that includes emerging alternatives and branched isomers. METHODS: 22 PFAS, including 10 linear legacy PFAS, 7 branched isomers, 3 short chain alternatives and 2 components of F53B [e.g., 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA)] were quantified in blood plasma among 740 healthy men. Five semen quality parameters (i.e., volume, count, concentration, total motility and progressive rate) were assessed. Multiple linear regression and three multiple pollutant models (i.e., adaptive elastic net regression, quantile based g-computation, and XGBoost method) were used to assess the associations of individual PFAS and PFAS mixture with semen quality and the potential interactive effects among congeners. RESULTS: After adjusting for selected confounders, perfluorobutane sulfonate (PFBS) and perfluorohexane sulfonate (PFHxS) presented significant and negative associations with sperm count [ßAENET = -0.09 (95%CI: -0.14, -0.03) for PFBS, and -0.16 (95%CI: -0.25, -0.07) for PFHxS] and sperm concentration [-0.04 (95%CI: -0.08, -0.001) for PFBS and -0.11 (95%CI: -0.17, -0.04) for PFHxS]. 6:2 Cl-PFESA showed negative associations with total motility (-2.33, 95%CI: -3.80, -0.86) and progressive rate (-1.46, 95%CI: -2.79, -0.12). But perfluoroheptanesulfonic acid (PFHpS) was positively associated with sperm count and concentration. These associations were supported by the importance assessment of these four congeners in XGBoost analyses. However, no associations were found between PFAS mixture or branched isomers and semen quality; nor were there significant interactions among PFAS congeners. CONCLUSIONS: In the current cross-sectional study, we found that two emerging PFAS replacements (i.e., 6:2 Cl-PFESA and PFBS) and PFHxS exposure were associated with reduced semen concentration, total sperm count and motility in men. Meanwhile, significant positive associations between PFHpS and sperm count and concentration were also observed. But there were no consistent associations between PFAS mixture, branched isomers and semen quality.

Quantifying Indirect Contribution from Precursors to Human Body Burden of Legacy PFASs Based on Paired Blood and One-Week Duplicate Diet.

The restriction on legacy perfluoroalkyl substances (PFASs) has led to increasing application and contamination of their precursors and novel alternatives. However, the indirect contribution from precursors has not been well characterized. In this study, 24 PFASs were measured in the paired human blood and urine from general volunteers (n = 20), as well as their corresponding exposure matrices (7 day duplicate diet, drinking water and dust). Perfluorooctanoic acid (PFOA) was predominant, followed by 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), contributing 21.6-47.0 and 6.6-20.0% of the total concentrations, respectively. Total oxidable precursor (TOP) assay and isomeric analysis coupled with a toxicokinetic model suggested that around 19% of perfluorooctane sulfonate (PFOS) in human was contributed by its precursors. The strong correlation between the estimated daily intake (EDI) and human blood concentration for 6:2 Cl-PFESA suggested that it was mainly contributed by direct exposure. The bioavailability of 6:2 Cl-PFESA in the food matrices was estimated as 18.6% by comparing the estimated and measured blood concentrations, implying that human exposure might be overestimated if the bioavailability of PFASs in food was not considered. Assuming that they had a similar bioavailability, it was estimated that ca. 20% of PFOS body burden was from indirect exposure to its precursors, which was supported by TOP assay.

Aerobic biotransformation of 6:2 fluorotelomer sulfonate by Dietzia aurantiaca J3 under sulfur-limiting conditions.

The polyfluorinated alkyl substance 6:2 fluorotelomer sulfonate (6:2 FTS) has been detected in diverse environments impacted by aqueous film-forming foams used for firefighting. In this study, a bacterial strain (J3) using 6:2 FTS as a sulfur source was isolated from landfill leachate previously exposed to polyfluoroalkyl substances in New South Wales, Australia. Strain J3 shares 99.9% similarity with the 16S rRNA gene of Dietzia aurantiaca CCUG 35676T. Genome sequencing yielded a draft genome sequence of 37 contigs with a G + C content of 69.7%. A gene cluster related to organic sulfur utilisation and assimilation was identified, that included an alkanesulfonate monooxygenase component B (ssuD), an alkanesulfonate permease protein (ssuC), an ABC transporter (ssuB), and an alkanesulfonate-binding protein (ssuA). Proteomic analyses comparing strain J3 cultures using sulfate and 6:2 FTS as sulfur source indicated that the ssu gene cluster was involved in 6:2 FTS biodegradation. Upregulated proteins included the SsuD monooxygenase, the SsuB transporter, the ABC transporter permease (SsuC), an alkanesulfonate-binding protein (SsuA), and a nitrilotriacetate monooxygenase component B. 6:2 Fluorotelomer carboxylic acid (6:2 FTCA) and 6:2 fluorotelomer unsaturated acid (6:2 FTUA) were detected as early degradation products in cultures (after 72 h) while 5:3 fluorotelomer acid (5:3 FTCA), perfluorohexanoic acid (PFHxA) and perfluoropentanoic acid (PFPeA) were detected as later degradation products (after 168 h). This work provides biochemical and metabolic insights into 6:2 FTS biodegradation by the Actinobacterium D. aurantiaca J3, informing the fate of PFAS in the environment.

Legacy and Emerging Poly- and Perfluoroalkyl Substances in Finless Porpoises from East China Sea: Temporal Trends and Tissue-Specific Accumulation.

Perfluoroalkyl sulfonates (PFSAs), perfluoroalkyl carboxylates (PFCAs), and emerging alternatives and precursors of these compounds were determined in tissues of finless porpoise (Neophocaena asiaeorientalis sunameri) collected from East China Sea in 2009-2010 and 2018-2019. The median hepatic concentrations of emerging poly- and perfluoroalkyl substances (PFASs), including 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), 2,3,3,3-tetrafluoro-2-propanoate (HFPO-DA), and 4,8-dioxa-3H-perfluorononanoate (ADONA) were 16.2, 2.16, < LOQ (limit of quantification) and < LOQ ng/g ww (wet weight), respectively. The concentrations of legacy substances, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA), were 86.9 and 1.95 ng/g ww, respectively. The liver concentrations of 6:2 Cl-PFESA, HFPO-DA, and perfluorohexanesulfonate (PFHxS) increased with time between 2009-2010 and 2018-2019. Further, concentrations of PFOA showed a declining trend in finless porpoise, whereas PFOS and its precursor (i.e., perfluorooctane sulfonamide [FOSA]) showed an increasing trend with time between 2009-2010 and 2018-2019. Analysis of PFASs in nine different tissues/organs of finless porpoise (i.e., liver, heart, intestine, spleen, kidney, stomach, lung, muscle, and skin) revealed a similar distribution pattern between 6:2 Cl-PFESA and PFOS; however, the tissue distribution patterns differed between HFPO-DA and PFOA. The concentrations of PFAS alternatives in kidney were similar or lower than the prototype compounds PFOS and PFOA (i.e., 8:2 Cl-PFESA < 6:2 Cl-PFESA ≈ PFOS; HFPO-DA < PFOA), implying slow renal excretion of PFAS alternatives as that of legacy PFASs. The estimates of body burdens of PFASs in porpoises suggested comparable accumulation of PFAS alternatives and legacy PFSAs and PFCAs. This study provides novel information on temporal trends and tissue distribution of emerging PFASs in marine mammals in China.

Monitoring Analysis of Perfluoroalkyl Substances and F-53B in Bottled Water, Tea and Juice Samples by LC-MS/MS.

Monitoring analysis of 14 per- and polyfluoroalkyl substances (PFAS), 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B) and dodecafluoro-3H-4,8-dioxanonanoate (ADONA) in bottled drinking water, tea and juice samples was performed using LC coupled with tandem mass spectrometry (LC-MS/MS) and solid-phase extraction (SPE). In the electrospray negative ion mode, the limit of detection and limit of quantification (LOQ) values were 0.1 to 0.8 ng/mL and 0.2 to 1.6 ng/mL, respectively. The calibration curves were linear from LOQ to 50 ng/mL (r2 > 0.999). The SPE procedure (Presep PFC-II) was utilized for sample preparation and recovery rates for three standards (35, 70 and 140 ng/L) were 80.4-118.8% with relative standard deviation (RSD) ≤ 0.6%. Using the developed method, various samples (n = 54) from Japanese markets were investigated for PFAS and F-53B contamination, and values below the LOQ were observed. It is concluded that for monitoring products in the Japanese market, our method represents a significant improvement over complex techniques for the quantification of PFAS and related compounds from various foods.