Perfluorooctanesulfonate Alternatives Research Articles

Photo-reductive decomposition of perfluorooctane sulfonate (PFOS) and its common alternatives by UV/VUV/sulfite process: Mechanism, kinetic modeling, and water matrix effects

The present study investigated the photo-reduction of perfluorooctane sulfonate (PFOS) and its alternatives, focusing on decomposition mechanisms, active species involvement, the influence of background water constituents, and kinetic model development. The decomposition and defluorination rates followed the order of PFOS > PFHxS > 6:2 FTSA > PFBS, with shorter chains and CH2 linkers enhancing the resistance of PFOS alternatives against the attack of hydrated electrons (eaq−). Two primary pathways were identified during the photodegradation of PFAS: (i) H/F exchange at CF bonds with the lowest bond dissociation energies (BDEs) and (ii) functional group cleavage followed by short-chain PFCAs formation, with OH playing a crucial role in transforming intermediates. Adding iodide and elevated temperatures demonstrated a synergistic effect on PFBS decomposition and defluorination, with high temperatures promoting functional group cleavage as the preferred defluorination pathway. The study examined the impact of background water constituents in different aqueous environments, from surface waters to wastewater streams and ion-exchange brine concentrates. Chloride exhibited a concentration-based dual impact on the UV/VUV/sulfite process: promotive effects at low dosages (1–10 mM) by acting as a secondary eaq− mediator, and adverse effects at high dosages (20–500 mM) due to the scavenging effect of generated chlorine radicals (Cl). High ionic strength adversely affected eaq− quantum efficiency. Additionally, bicarbonate and natural organic matter (NOM) had opposing effects on PFOS photo-reduction, primarily through eaq− scavenging and pH alteration. Kinetic modeling revealed reaction rate constants of the studied PFAS with eaq− ranging from 1.8 × 106 to 1.3 × 109 M−1 s−1, corroborating the concentration profiles of active species and highlighting the reductive nature of sulfite-mediated processes.

Hepatotoxicity induced in rats by chronic exposure to F–53B, an emerging replacement of perfluorooctane sulfonate (PFOS)

A plethora of studies have shown the prominent hepatotoxicity caused by perfluorooctane sulfonate (PFOS), yet the research on the causality of F–53 B (an alternative for PFOS) exposure and liver toxicity, especially in mammals, is largely limited. To investigate the effects that chronic exposure to F–53 B exert on livers, in the present study, male SD rats were administrated with F–53 B in a certain dose range (0, 1, 10, 100, 1000 μg/L, eight rats per group) for 6 months via drinking water and the hepatotoxicity resulted in was explored. We reported that chronic exposure to 100 and 1000 μg/L F–53 B induced remarkable histopathological changes in liver tissues such as distinct swollen cells and portal vein congestion. In addition, the increase of cytokines IL-6, IL-2, and IL-8 upon long-term administration of F–53 B demonstrated the high level of inflammation. Moreover, F–53 B exposure was revealed to disrupt the lipid metabolism in the rat livers, mainly manifesting as the upregulation of some proteins involved in lipid synthesis and degradation, including ACC, FASN, SREBP-1c as well as ACOX1. These findings provided new evidence for the adverse effects caused by chronic exposure to F–53 B in rodents. It is crucial for industries, regulatory agencies as well as the public to remain vigilant about the adverse health effects associated with the emerging PFOS substitutes such as F–53 B. Implementation of regular monitoring and risk assessments is of great importance to alleviate environmental concerns towards PFOS alternatives exposure, and furthermore, to minimize the latent health risks to the public health.

Occurrence, source apportionment, and ecological risk of legacy and emerging per- and poly-fluoroalkyl substances (PFASs) in the Dahei river basin of a typical arid region in China

Per- and poly-fluoroalkyl substances (PFASs) are artificial chemicals with broad commercial and industrial applications. Many studies about PFASs have been conducted in densely industrial and populated regions. However, fewer studies have focused on the PFASs’ status in a typical arid region. Here, we investigated 30 legacy and emerging PFASs in surface water from the mainstream and tributaries of the Dahei River. Our results revealed that total PFASs concentrations (∑30PFASs) in water ranged from 3.13 to 289.1 ng/L (mean: 25.40 ng/L). Perfluorooctanoic acid (PFOA) had the highest mean concentration of 2.44 ng/L with a 100% detection frequency (DF), followed by perfluorohexanoic acid (PFHxA) (mean concentration: 1.34 ng/L, DF: 59.26%). Also, perfluorohexane sulfonate (DF: 44.44%), perfluorobutane sulfonate (DF: 88.89%), and perfluorooctane sulfonate (PFOS) (DF: 92.59%) had mean concentrations of 12.94, 2.00, and 1.05 ng/L, respectively. Source apportionment through ratio analysis and principal component analysis-multiple linear regression analysis showed that treated or untreated sewage, aqueous film-forming foam, degradation of precursors, and fluoropolymer production were the primary sources. The PFOS alternatives were more prevalent than those of PFOA. Conductivity, total phosphorus, and chlorophyll a positively correlated with Σ30PFASs and total perfluoroalkane sulfonates concentrations. Furthermore, ecological risk assessment showed that more attention should be paid to perfluorooctadecanoic acid, perfluorohexadecanoic acid, perfluorooctane sulfonate, perfluorohexane sulfonate, and (6:2 and 6:2/8:2) polyfluoroalkyl phosphate mono- and di-esters. The mass load of PFASs to the Yellow River was 1.28 kg/year due to the low annual runoff in the Dahei River in the arid region. This study provides baseline data for PFASs in the Dahei River that can aid in the development of effective management strategies for controlling PFASs pollution in typical arid regions in China.

Adverse impacts of environmentally relevant PFOS alternatives on mice pancreatic tissues

Perfluorooctane sulfonate (PFOS) alternatives are chemicals that are used to make a range of products. Researchers have found that PFOS alternatives are probably no less toxic than PFOS, which has aroused concern. It has also revealed that the pancreas may be harmed by exposure to PFOS alternatives. However, there is insufficient evidence to demonstrate the toxicity mechanisms of PFOS alternatives. This study demonstrates the adverse effects of three PFOS alternatives on the pancreatic health of mice. After subchronic exposure to PFOS alternatives at environmentally relevant concentrations (800 μg/L perfluorohexanesulfonate, 800 μg/L perfluorobutanesulfonate, and 3 μg/L sodium ρ-perfluorous nonenoxybenzene sulfonate) via drinking water for 6 weeks, toxicity mechanisms were elucidated by examining histopathology, immunity, endoplasmic reticulum stress, 16S rRNA, and short-chain fatty acid targeted metabolomics. Sodium ρ-perfluorous nonenoxybenzene sulfonate significantly increased levels of TNF-α, IL-6, p-PERK, and ATF-4 and decreased the abundance of Akkermansia muciniphila and Lactobacillus reuteri. In addition, the three PFOS alternatives changed the composition of the gut microbiota in mice. Short-chain fatty acids, which are metabolites of the gut microbiota, also significantly decreased. Correlation analysis demonstrates that the alteration of gut microbes is related to the adverse effects on the mice pancreas. Results suggest that the murine pancreas may be toxic endpoints of PFOS alternatives. This study alerts the threats to human health and accelerates the toxicology research of an increasing number of emerging PFOS alternatives.

Bioaccumulation, tissue distribution, and maternal transfer of novel PFOS alternatives (6:2 Cl-PFESA and OBS) in wild freshwater fish from Poyang Lake, China

As emerging alternatives to perfluorooctane sulfonate (PFOS), 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and sodium p-perfluorous nonenox-benzenesulfonate (OBS) were frequently detected in the four freshwater fish species collected from Poyang Lake. Median concentrations of 6:2 Cl-PFESA and OBS in fish tissues were 0.046–6.0 and 0.46–5.1 ng/g wet weight, respectively. The highest concentrations of 6:2 Cl-PFESA was found in fish livers, whereas OBS was found in the pancreas, brain, gonads, and skin. The tissue distribution pattern of 6:2 Cl-PFESA is similar to that of PFOS. The tissue/liver ratios of OBS were higher than those of PFOS, suggesting that OBS has a greater tendency to transfer from the liver to other tissues. The logarithmic bioaccumulation factors (log BAFs) of 6:2 Cl-PFESA in three carnivorous fish species were greater than 3.7, whereas those of OBS were less than 3.7, indicating that 6:2 Cl-PFESA had a strong bioaccumulation potential. Notably, sex- and tissue-specific bioaccumulation of OBS has also been observed in catfish. Most tissues (except the gonads) exhibited higher OBS concentrations in males than in females. However, no differences were found for 6:2 Cl-PFESA and PFOS. Maternal transfer efficiency of OBS was higher than that of 6:2 Cl-PFESA and PFOS in catfish (p < 0.05), indicating that OBS presents a higher risk of exposure to males and offspring through maternal offloading.

Insights into the circadian rhythm alterations of the novel PFOS substitutes F-53B and OBS on adult zebrafish

As alternatives to perfluorooctane sulfonate (PFOS), 6:2 Cl-PFESA (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) are frequently detected in aquatic environments, but little is known about their neurotoxicity, especially in terms of circadian rhythms. In this study, adult zebrafish were chronically exposed to 1 μM PFOS, F-53B and OBS for 21 days taking circadian rhythm-dopamine (DA) regulatory network as an entry point to comparatively investigate their neurotoxicity and underlying mechanisms. The results showed that PFOS may affect the response to heat rather than circadian rhythms by reducing DA secretion due to disruption of calcium signaling pathway transduction caused by midbrain swelling. In contrast, F-53B and OBS altered the circadian rhythms of adult zebrafish, but their mechanisms of action were different. Specifically, F-53B might alter circadian rhythms by interfering with amino acid neurotransmitter metabolism and disrupting blood-brain barrier (BBB) formation, whereas OBS mainly inhibited canonical Wnt signaling transduction by reducing cilia formation in ependymal cells and induced midbrain ventriculomegaly, finally triggering imbalance in DA secretion and circadian rhythm changes. Our study highlights the need to focus on the environmental exposure risks of PFOS alternatives and the sequential and interactive mechanisms of their multiple toxicities.

Aberrant hepatic lipid metabolism associated with gut microbiota dysbiosis triggers hepatotoxicity of novel PFOS alternatives in adult zebrafish.

Perfluorooctane sulfonate (PFOS) has been reported to induce hepatotoxicity in wildlife and humans. Novel PFOS alternatives have been widely used following restrictions on PFOS, but little is known about their potential toxicity. Here, the first comprehensive investigation on the chronic hepatotoxicity and underlying molecular mechanisms of PFOS, 6:2Cl-PFESA (F-53B), and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) was carried out on adult zebrafish through a histopathological examination, biochemical measurement, and multi-omics analysis. PFOS and its alternatives caused changes in liver histopathology and liver function indices in the order of F-53B>PFOS>OBS, which was consistent with their concentration in the liver. In silico modeling and transcriptional profiles suggested that the aberrant hepatic lipid metabolism induced by F-53B and PFOS was initiated by the action on peroxisome proliferator-activated receptor γ (PPARγ), which triggered changes in downstream genes transcription and led to an imbalance between lipid synthesis and expenditure. Gut microbiome analysis provided another novel mechanistic perspective that changes in the abundance of Legionella, Ralstonia, Brevundimonas, Alphaproteobacteria, Plesiomonas, and Hyphomicrobium might link to alterations in the PPAR pathway based on their significant correlation. This study provides insight into the molecular mechanisms of hepatotoxicity induced by PFOS and its novel alternatives and highlights the need for concern about their environmental exposure risks.

Concentration-dependent toxicokinetics of novel PFOS alternatives and their chronic combined toxicity in adult zebrafish

The increasing use of perfluorooctanesulfonate (PFOS) alternatives has led to their release into the aquatic environment. This study sought to determine the effects of exposure concentration on the toxicokinetics of PFOS and its alternatives, including perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzenesulfonate (OBS) in adult zebrafish by exposure to mixtures of the five per- and polyfluoroalkyl substances (PFAS) at 1, 10, and 100 ng/mL for 28-day, followed by a 14-day depuration. PFAS predominantly accumulated in the blood and liver, and the bioconcentration factor (BCF) decreased in the order of F-53B > PFOS > OBS ≫ PFHxS > PFBS in whole-fish homogenates. The uptake rate constants and BCF of the short-chain PFAS (≤C6) positively correlated with increasing exposure concentration, while the long-chain PFAS (≥C8) exhibited a pattern of first increasing and then decreasing. A consistent increase in the elimination rate constants of short- and long-chain PFAS was observed with increasing exposure concentration. All PFAS form tight conformations with ZSA and ZL-FABP via hydrogen bonding as revealed by molecular docking analysis. Furthermore, chronic combined exposure to PFAS induced the occurrence of vacuolation and oxidative stress in the zebrafish liver. Our findings uniquely inform the concentration-dependent bioconcentration potential and health risks to aquatic organisms of these PFOS alternatives in the environment.

Chlorinated Polyfluorinated Ether Sulfonates and Thyroid Hormone Levels in Adults: Isomers of C8 Health Project in China.

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (μIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

An Investigation of Thermal Air Degradation and Pyrolysis of Per- and Polyfluoroalkyl Substances and Aqueous Film-Forming Foams in Soil

In this study, we found that thermal decomposition of per- and polyfluoroalkyl substances (PFAS) in soil was rapid at moderate temperatures of 400–500 °C, regardless of whether the soil was contaminated by a single PFAS compound or a PFAS mixture in aqueous film-forming foams. Substantial degradation (>99%) of PFAS in soil, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), short-chain homologues, cationic and zwitterionic precursors, and PFOA and PFOS alternatives, occurred in 30 min at 500 °C in both a sealed reactor in air and a horizontal reactor under a continuous flow of N2. The effect of the initial PFAS level in soil (0.001–10 μmol/g) and soil texture was insignificant, provided a sufficiently high temperature was applied. Furthermore, this study showed, for the first time, that kaolinite dramatically decreased the apparent yield of F from PFAS heated at >300 °C, likely due to the chemisorption of F radicals on kaolinite. This phenomenon was not observed when kaolinite and an inorganic fluoride salt (NaF) were thermally treated. Lastly, various nonpolar thermal degradation products of PFOA and PFOS were reported for the first time. The profile of fluorinated volatiles, particularly perfluoroalkenes, was similar between these two chemicals. The results support a radical-mediated degradation pathway of PFAS.

Perfluorooctane sulfonate alternatives and metabolic syndrome in adults: New evidence from the Isomers of C8 Health Project in China

Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives.

Novel and legacy poly- and perfluoroalkyl substances (PFASs) in indoor dust from urban, industrial, and e-waste dismantling areas: The emergence of PFAS alternatives in China

With the phase out of perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), the composition profiles of poly- and perfluoroalkyl substance (PFAS) in our living environment are unclear. In this study, 25 PFASs were analyzed in indoor dust samples collected from urban, industrial, and e-waste dismantling areas in China. PFOS alternatives, including 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) (median: 5.52 ng/g) and 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA) (1.81 ng/g), were frequently detected. By contrast, PFOA alternatives, such as hexafluoropropylene oxide dimer acid (HPFO-DA, Gen-X) and ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA), were not found in any of the dust samples. As expected, all legacy PFASs were widely observed in indoor dust, and 4 PFAS precursors were also detected. Dust concentrations of 6:2 Cl-PFESA were strongly correlated (p < 0.05) with those of 8:2 Cl-PFESA regardless of sampling sites. 6:2 Cl-PFESA was also significantly associated with that of PFOS in industrial and e-waste (p < 0.01) areas. Association analysis suggested that the sources of PFOS and its alternatives are common or related. Although ∑Cl-PFESA concentration was lower than that of PFOS (17.4 ng/g), industrial areas had the highest 6:2 Cl-PFESA/PFOS ratio (0.63). Composition profiles of PFASs in the industrial area showed the forefront of fluorine change. Thus, the present findings suggested that Cl-PFESAs are widely used as PFOS alternatives in China, and high levels of human Cl-PFESA exposure are expected in the future. Short-chain PFASs (C4–C7) were the predominant PFASs found in dust samples, contributing to over 40% of ∑total PFASs. Furthermore, perfluoro-1-butanesulfonate/PFOS and perfluoro-n-butanoic acid (PFBA)/PFOA ratios were 2.8 and 0.72, respectively. These findings suggested shifting to the short-chain PFASs in the environment in China. To the authors knowledge this is the first study to document the levels of 6:2 Cl-PFESA, 8:2 Cl-PFESA in indoor dust.

Legacy per- and polyfluoroalkyl substances (PFASs) and alternatives (short-chain analogues, F-53B, GenX and FC-98) in residential soils of China: Present implications of replacing legacy PFASs

With the worldwide regulation of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the alternatives (short chain analogues and emerging per- and polyfluoroalkyl substances, PFASs) have gradually attracted global attention. This study analysed the replacing of legacy PFASs in China using PFASs data from residential soils, which might be good environmental indicators of their present usage. The total concentrations of 21 PFASs ranged from 244 to 13564 pg/g, and PFOA was the dominant compound among the studied PFASs, with a concentration of 354 ± 439 pg/g. Serious PFASs pollution in residential soils mainly occurred in Eastern Coastal China as a result of locally developed industry and economies. Weak but significant correlations were found between PFASs and environmental and socioeconomic factors, suggesting that various factors determine PFASs contamination in residential soils. The concentration and detection frequency (DF) of short-chain analogues (C < 8) (375 ± 509 pg/g and 100%), and F-53B (216 ± 306 pg/g and 98.9%) were higher than those for PFOS (193 ± 502 pg/g and 85.4%), indicating that these compounds have been widely used as PFOS alternatives and their consumption has already exceeded that of PFOS in China. In addition, GenX (the PFOA alternative) had a concentration and DF of 19.1 ± 104 pg/g and 40.5%, respectively. These values were much lower than those for PFOA (354 ± 439 pg/g and 96.6%), indicating GenX consumption is still limited at the national scale of China, despite its use as a PFOA replacement. Moreover, the low concentration and DF of FC-98 (2.31 ± 11.1 pg/g and 27.0%) indicate that its consumption might be negligible. Our study demonstrated that short chain analogues and emerging alternatives have become the dominant PFAS pollutants in Chinese residential soils, and further studies need to be conducted to understand their toxicity and environmental risks.

Are perfluorooctane sulfonate alternatives safer? New insights from a birth cohort study

BackgroundExperimental studies show that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA 6:2 and 8:2), one of perfluoroalkyl substances (PFAS) used as perfluorooctane sulfonate (PFOS) alternatives, are reproductive toxicants in vivo and in vitro. However, the associations between gestational exposure to Cl-PFESAs and birth outcomes are unknown. ObjectivesWe investigated associations between 6:2 Cl-PFESA and 8:2 Cl-PFESA in maternal serum and birth outcomes. MethodsWe measured four PFAS, including 6:2 Cl-PFESA, 8:2 Cl-PFESA, PFOS, and perfluorooctanoic acid (PFOA) in third-trimester maternal serum collected from 372 mother-child dyads participating in the Guangzhou Birth Cohort Study. Characteristics of mothers and infants were gathered from medical records and by interviewer-administered questionnaires. ResultsPFOS was the most abundant PFAS in maternal serum (median: 7.15 ng/mL), followed by 6:2 Cl-PFESA (median: 2.41 ng/mL). Greater maternal serum levels of all PFAS alternatives were significantly associated with lower birth weight, adjusted for confounding variables. For example, each ln-ng/mL greater concentration of 6:2 Cl-PFESA and 8:2 Cl-PFESA was associated with a 54.44 g [95% confidence interval (CI): −95.66, −13.22] and 21.15 g (95% CI: −41.44, −0.86) lower birth weight, respectively. Greater continuous maternal serum 6:2 Cl-PFESA (OR: 2.67, 95% CI: 1.73, 4.15) and PFOS (OR: 2.03, 95% CI: 1.24, 3.32) were also associated with higher risks for preterm birth, adjusted for confounders, with a possible threshold effect at the highest quartile of 6:2 Cl-PFESA. ConclusionsFor the first time, we report associations between maternal serum 6:2 Cl-PFESA and 8:2 Cl-PFESA concentrations and adverse birth outcomes. Our findings suggest that PFOS alternatives may be reproductive toxicants in human populations and should be considered with caution before widespread use. Given the preliminary nature of our results, additional epidemiological and toxicological investigations are needed to more definitively assess the risks.

Screening of Potential PFOS Alternatives To Decrease Liver Bioaccumulation: Experimental and Computational Approaches

Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant with significant bioaccumulation potential in liver tissues. Exposure to PFOS could cause increase of liver weight, induce adenomas of the liver, and cause hepatomegaly. Alternatives of PFOS might be designed and synthesized that have significantly lower liver bioaccumulation. In this study, we conducted animal exposure experiments to investigate tissue accumulations of 14 per- and polyfluoroalkyl substances. Correlation analysis demonstrated that accumulation of the compounds in rat liver had strong correlations with their binding affinities of liver fatty acid binding protein (LFABP). Thus, we combined a quantitative structure-activity relationship model with molecular dynamics (MD) simulations to develop computational models to predict the LFABP binding affinities of two newly synthesized alternatives, perfluorodecalin-2-sulfonic acid and N-diperfluorobutanoic acid. The binding characteristics of the PFOS alternatives for LFABP were elaborated to explore how the different structural modifications of molecules influenced the underlying binding mechanisms. Subsequent animal experiments demonstrated that the binding free energy calculations based on the MD simulations provided a good indicator to reflect the relative degree of liver accumulation of the PFOS alternatives in the same exposure doses and durations. Our findings from the combination of experimental exposure and computational model can provide helpful information to design potential alternatives of PFOS with weak LFABP binding capability and low liver accumulation.

Developmental Toxicity of Perfluorooctanesulfonate (PFOS) and Its Chlorinated Polyfluoroalkyl Ether Sulfonate Alternative F-53B in the Domestic Chicken.

The chlorinated polyfluoroalkyl ether sulfonate F-53B is used as a mist suppressant in the Chinese electroplating industry. Because of the regulations on perfluorooctanesulfonate (PFOS), its use is expected to increase. Until now, F-53B toxicity data have been scarce and are, to our knowledge, lacking for birds. This study therefore investigated the effects of PFOS and F-53B, separately and as mixtures, on the development of the chicken ( Gallus gallus domesticus). Compounds were injected in ovo, before incubation, at 150 and 1500 ng/g egg. At embryonic day 20, a significantly lower heart rate was observed in all treated groups compared to the control group and hatchlings exposed to the high dose of F-53B had a significantly enlarged liver (8%). Embryonic survival was not affected and no significant effects on hatchling body mass or oxidative stress parameters were found. Our results suggest that these compounds likely have different toxicity thresholds for the investigated endpoints, and/or different modes of action. This study thereby underlines the potential developmental toxicity of PFOS and F-53B at environmentally relevant concentrations. Assessment of PFOS alternatives should therefore continue, preferably prior to their large scale use, as they should be ensured to be less harmful than PFOS itself.

Elevated concentrations of perfluorohexanesulfonate and other per- and polyfluoroalkyl substances in Baiyangdian Lake (China): Source characterization and exposure assessment

Novel 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) and legacy PFASs, such as perfluorohexane sulfonate (PFHxS), have been used to replace perfluorooctane sulfonate (PFOS), a known persistent organic pollutant. Thus, it is critical to understand these PFOS alternatives regarding their sources and concentrations in the natural environment. In this study, 41 surface water samples as well as edible aquatic organisms were collected from Baiyangdian Lake, the largest freshwater lake in Hebei Province, China. Perfluorooctanoate acid (PFOA) and PFHxS were the predominant PFASs detected in the surface water, reaching concentrations of 8 397.23 ng/L and 1 478.03 ng/L, respectively, with PFHxS accounting for the greatest proportion (∼80.00%) in most water samples. PFHxS (mean: 87.53 ng/g) and PFOS (mean: 35.94 ng/g) were also the most prevalent compounds detected in aquatic organisms. Estimated daily intake (EDI) values of PFOS (16.56 ng/kg bw/d) and PFHxS (16.11 ng/kg bw/d) via aquatic food and drinking water were the highest among PFASs, indicating potential exposure risks to residents. In addition, fish product consumption was the important exposure pathway for residents to PFOA, PFHxS, PFOS, and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA). This study reports on the highest PFHxS levels ever recorded in surface water, suggesting that further quantification of PFHxS in human serum and assessment of its health risks to local residents are warranted and critical.

Distribution, source identification and health risk assessment of PFASs and two PFOS alternatives in groundwater from non-industrial areas

Little research has been carried out for the per- and polyfluoroalkyl substances (PFASs) in groundwater from non-industrial areas, even though it has been proved that PFASs can transport for long distance. In this study, the concentration profiles and geographical distribution of 14 PFASs, including two alternatives of perfluorooctane sulfonate (PFOS), 6:2 fluorotelomer sulfonate (6:2 FTS) and potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B), were analyzed in groundwater samples (n = 102) collected from water wells in non-industrial areas. The total concentrations of PFASs (Σ14PFASs) in groundwater samples ranged from 2.69 to 556 ng/L (mean 43.1 ng/L). The detection rates of shorter chain (C4-C9) PFASs were 62.75–100%, higher than those of long chain (> C10) PFASs with detection rates of less than 40%. The source identification using hierarchical cluster analysis and Spearman rank correlation analysis suggested that domestic sewage and atmospheric deposition may contribute significantly to the PFAS occurrence in groundwater in non-industrial areas, while the nearby industrial parks may contribute some, but not at a significant level. Furthermore, the human health risk assessment analysis shows that the health hazards associated with perfluorooctanoic acid (PFOA) and PFOS, two of the main PFAS constituents in groundwater from non-industrial areas, were one or two orders of magnitude higher than those in a previous study, but were unlikely to cause long-term harm to the residents via the drinking water exposure pathway alone.

Chlorinated Polyfluorinated Ether Sulfonates Exhibit Higher Activity toward Peroxisome Proliferator-Activated Receptors Signaling Pathways than Perfluorooctanesulfonate.

Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs) are the alternative products of perfluorooctanesulfonate (PFOS) in the metal plating industry in China. The similarity in chemical structures between Cl-PFAESs and PFOS makes it reasonable to assume they possess similar biological activities. In the present study, we investigated whether Cl-PFAESs could induce cellular effects through peroxisome proliferator-activated receptors (PPARs) signaling pathways like PFOS. By using fluorescence competitive binding assay, we found two dominant Cl-PFAESs (6:2 Cl-PFAES and 8:2 Cl-PFAES) bound to PPARs with affinity higher than PFOS. Based on the luciferase reporter gene transcription assay, the two Cl-PFAESs also showed agonistic activity toward PPARs signaling pathways with potency similar to (6:2 Cl-PFAES) or higher than (8:2 Cl-PFAES) PFOS. Molecular docking simulation showed the two Cl-PFAESs fitted into the ligand binding pockets of PPARs with very similar binding mode as PFOS. The cell function results showed Cl-PFAESs promoted the process of adipogenesis in 3T3-L1 cells with potency higher than PFOS. Taken together, we found for the first time that Cl-PFAESs have the ability to interfere with PPARs signaling pathways, and current exposure level of 6:2 Cl-PFAES in occupational workers has exceeded the margin of safety. Our study highlights the potential health risks of Cl-PFAESs as PFOS alternatives.

Chlorinated Polyfluoroalkyl Ether Sulfonic Acids in Matched Maternal, Cord, and Placenta Samples: A Study of Transplacental Transfer.

Currently, information regarding concentrations of chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) in human placenta does not exist. The main objective of this study was to assess the occurrence and distribution of two Cl-PFESAs, 6:2 Cl-PFESA and 8:2 Cl-PFESA, in maternal serum, umbilical cord serum, and placenta to better assess the transport pathways related to human prenatal exposure. The widely studied perfluorooctanesulfonate (PFOS) was studied for comparison. This study was a hospital-based survey involving quantitative determination of Cl-PFESA and PFOS concentrations in maternal serum (n = 32), cord serum (n = 32), and placenta (n = 32) samples from women in Wuhan, China. The results indicate that Cl-PFESAs can efficiently be transported across placenta, with median exposure levels of 0.60 and 0.01 ng/mL for 6:2 Cl-PFESA and 8:2 Cl-PFESA in the cord sera, respectively. Concentrations of the target compounds in maternal sera, cord sera, and placentas decreased in the following order: PFOS > 6:2 Cl-PFESA > 8:2 Cl-PFESA. Similar patterns were observed in maternal sera, cord sera, and placentas for Cl-PFESAs, with concentrations decreasing in the following order: maternal sera > cord sera > placentas. Significant correlations were observed among 6:2 Cl-PFESA, 8:2 Cl-PFESA, and PFOS concentrations in the maternal serum, cord serum, and placenta samples (r > 0.7; p < 0.001). The median value of RCM (ratio of cord serum to maternal serum concentration) of 6:2 Cl-PFESA was 0.403, indicating a relatively high (∼40%) placental transfer efficiency. 8:2 Cl-PFESA was transported across placenta to a greater extent than 6:2 Cl-PFESA was, likely because of its higher hydrophobicity and lower plasma protein binding affinity. To the best of our knowledge, this is the first study to report the occurrence and distribution of 6:2 Cl-PFESA and 8:2 Cl-PFESA in human placenta. The findings improve our understanding of the mechanisms of transplacental transfer and neonatal exposure to these important PFOS alternatives.