Legacy Perfluoroalkyl Substances Research Articles

Sub-acute exposure of male guppies (Poecilia reticulata) to environmentally relevant concentrations of PFOA and GenX induces significant changes in the testis transcriptome and reproductive traits

Poly- and perfluoroalkyl substances (PFAS) are frequently detected in the environment and are linked to adverse reproductive health outcomes in humans. Although legacy PFAS have been phased out due to their toxicity, alternative PFAS are increasingly used despite the fact that information on their toxic effects on reproductive traits is particularly scarce. Here, we exposed male guppies (Poecilia reticulata) for a short period (21 days) to an environmentally realistic concentration (1 ppb) of PFOA, a legacy PFAS, and its replacement compound, GenX, to assess their impact on reproductive traits and gene expression. Exposure to PFAS did not impair survival but instead caused sublethal effects. Overall, PFAS exposure caused changes in male sexual behaviour and had detrimental effects on sperm motility. Sublethal variations were also seen at the transcriptional level, with the modulation of genes involved in immune regulation, spermatogenesis, and oxidative stress. We also observed bioaccumulation of PFAS, which was higher for PFOA than for GenX. Our results offer a comprehensive comparison of these two PFAS and shed light on the toxicity of a newly emerging alternative to legacy PFAS. It is therefore evident that even at low concentrations and with short exposure, PFAS can have subtle yet significant effects on behaviour, fertility, and immunity. These findings underscore the potential ramifications of pollution under natural conditions and their impact on fish populations.

Perfluorooctanesulfonic Acid Alters Pro-Cancer Phenotypes and Metabolic and Transcriptional Signatures in Testicular Germ Cell Tumors.

The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recently emergent human and environmental health concern. There is a consistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is relatively strong evidence linking PFAS and testicular germ cell tumors (TGCTs). However, no mechanistic studies have been performed to date concerning PFAS and TGCTs. In this report, the effects of the legacy PFAS perfluorooctanesulfonic acid (PFOS) and the newer "clean energy" PFAS lithium bis(trifluoromethylsulfonyl)imide (LiTFSi, called HQ-115), on the tumorigenicity of TGCTs in mice, TGCT cell survival, and metabolite production, as well as gene regulation were investigated. In vitro, the proliferation and survival of both chemo-sensitive and -resistant TGCT cells were minimally affected by a wide range of PFOS and HQ-115 concentrations. However, both chemicals promoted the growth of TGCT cells in mouse xenografts at doses consistent with human exposure but induced minimal acute toxicity, as assessed by total body, kidney, and testis weight. PFOS, but not HQ-115, increased liver weight. Transcriptomic alterations of PFOS-exposed normal mouse testes were dominated by cancer-related pathways and gene expression alterations associated with the H3K27me3 polycomb pathway and DNA methylation, epigenetic pathways that were previously showed to be critical for the survival of TGCT cells after cisplatin-based chemotherapy. Similar patterns of PFOS-mediated gene expression occurred in PFOS-exposed cells in vitro. Metabolomic studies revealed that PFOS also altered metabolites associated with steroid biosynthesis and fatty acid metabolism in TGCT cells, consistent with the proposed ability of PFAS to mimic fatty acid-based ligands controlling lipid metabolism and the proposed role of PFAS as endocrine disrupters. Our data, is the first cell and animal based study on PFAS in TGCTs, support a pro-tumorigenic effect of PFAS on TGCT biology and suggests epigenetic, metabolic, and endocrine disruption as potential mechanisms of action that are consistent with the non-mutagenic nature of the PFAS class.

Occurrence, mass loading, and post-control temporal trend of legacy perfluoroalkyl substances (PFASs) in the middle and lower Yangtze River

Present study focused on per- and polyfluoroalkyl substances (PFASs) occurrence in dry and wet seasons in the middle and lower Yangtze River (YZR) and changing temporal trends after years of control. Results revealed that perfluorooctanoic acid (PFOA) was 75 % of total PFAS concentrations (∑11PFASs). ∑11PFASs were ranged 0.20–28.49 ng/L and 1.17–112.84 μg/kg in water and sediment. The logKoc of perfluoroalkyl carboxylic acids was positive with the carbon chain length (p < 0.05, r2 = 0.78). A meta-analysis of results from 16 peer-reviewed publications about PFASs in the YZR showed that fluorochemical industries strongly influenced the high PFAS levels in the detected scenes. PFOA was still the primary pollutant. Individual PFAS in the lower reach was higher than those in the middle reach. The mass loading of PFASs imported into the sea was 10.80 t/y. This study will help develop effective approaches for controlling emerging pollutants in the YZR.

Higher serum concentrations of PFAS among pesticide exposed female greenhouse workers

BackgroundLong-chained poly- and perfluoroalkyl substances (PFAS) have been used in pesticide formulations but their potential impact on human PFAS exposure has not been addressed. ObjectivesTo investigate if occupationally pesticide exposed female greenhouse workers in Denmark had higher serum concentrations of PFAS than a comparable background population. MethodsSerum samples collected between 1996 and 2001 from 181 pregnant greenhouse workers and a contemporary urban population of 48 pregnant women were analyzed for eight PFAS: perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorooctane sulfonamide (FOSA), N-methyl perfluorooctane sulfonamido acetic acid (N-MeFOSAA), and N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA). ResultsThe concentrations of PFOA, PFOS, and the PFOS precursors N-MeFOSAA, N-EtFOSAA, and FOSA were higher, and PFHxS was lower, among greenhouse workers than the comparison population. After adjusting for age and parity, serum concentrations of N-MeFOSAA, N-EtFOSAA, and FOSA were 2-to-3-fold higher, and the major PFAS in serum, PFOS and PFOA, were 30–50 % higher among the greenhouse workers. ConclusionHigher serum concentrations of some legacy PFAS among female greenhouse workers indicate that exposure to pesticides is a potential pathway of exposure. Although PFAS use in pesticide applications may appear to be a minor source of exposure for the general population, this pathway deserves attention in risk assessment.

Legacy perfluoro-alkyl substances impair LDL-cholesterol uptake independently from PCSK9-function

Perfluoro-alkyl substances (PFAS) are pollutants, whose exposure was associated with altered levels of low-density lipoproteins (LDL) in humans. Here we investigated this clinical outcome in two groups of young male adults residing in areas of respectively low and high environmental exposure to perfluoro-octanoic-acid (PFOA). From the Regional Authority data on pollution areas, 38 not-exposed and 59 exposed age-matched participants were evaluated for serum levels of total cholesterol (Total-Chol), LDL-Chol, high-density lipoprotein cholesterol (HDL-Chol), triglycerides (Tgl) and chromatography quantified PFOA. Human hepato-carcinoma cell line HepG2 was exposed to PFOA or perfluoro-octane-sulfonate (PFOS), as legacy PFAAs, and C6O4 as new generation compound. Fluorimetry was used to evaluate the cell-uptake of labelled-LDL. Proprotein Convertase Subtilisin/Kexin 9 (PCSK9)-mediated LDL-receptor (LDL-R) degradation and sub-cellular localization of LDL-R were evaluated by western blot analysis. Serum levels of PFOA, were positively and significantly correlated with Total-Chol (ρ = 0.312, P = 0.002), LDL-Chol (ρ = 0.333, P = 0.001) and Tgl (ρ = 0.375, P < 0.001). Participants with high serum LDL-Chol and Tgl levels, according to the cardiovascular risk, were more prevalent in exposed compared to not-exposed subjects (respectively: 23.7% vs 5.3%, P = 0.023 and 18,6% vs 0%, P = 0.006). Exposure of HepG2 cells to PFOA or C6O4 100 ng/mL was associated with a significantly lower LDL uptake than controls but no major impact of any PFAAs on PCSK9-mediated LDL-R degradation was observed. Compared to controls, exposure to PFAS showed an unbalanced LDL-R partition between membrane and cytoplasm. Endocytosis inducer sphingosine restored LDL-R partition only in samples exposed to C6O4. These data suggest a novel endocytosis-based mechanism of altered lipid trafficking associated with the exposure to legacy PFAS.

Presence of Perfluoroalkyl Substances in Landfill Adjacent Surface Waters in North Carolina.

Landfills pose an important public health risk, especially in historically disenfranchised communities that are disproportionately sited for landfills and in rural areas where private wells may be impacted. Landfills are major sources of perfluoroalkyl substances (PFAS) that migrate into the surrounding environment. This study characterized PFAS in surface waters adjacent to two landfills, one in Sampson County (SC) and one in Orange County (OC) in North Carolina. In addition to municipal solid waste and construction and demolition waste, the landfill in SC accepts industrial sludge from a chemical plant that produces proprietary PFAS. Over four months, 35 surface water samples were collected at upstream, landfill-adjacent, and downstream/downgradient sites. Thirty-four PFAS were analyzed using liquid chromatography with tandem mass spectroscopy. Of those, six novel and six legacy PFAS were detected. Legacy PFAS were detected in surface water near both landfills, with the highest concentrations adjacent to the landfill. Novel PFAS were only detected in surface water near the SC landfill and showed the highest concentrations adjacent to the landfill, indicating offsite migration of PFAS. These findings support the need for more comprehensive and frequent monitoring of groundwater and surface water wells near landfills and stricter regulation regarding the landfilling of industrial materials.

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.

Emerging poly- and perfluoroalkyl substances in water and sediment from Qiantang River-Hangzhou Bay

Many emerging poly- and perfluoroalkyl substances (PFASs) are being used in China, due to the gradual phase out of legacy PFASs. Occurrence and environmental behaviors of emerging PFASs in Chinese fresh water environment are still not well known. In this study, 31 PFASs, including 14 emerging PFASs, were measured in 29 pairs of water and sediment samples from Qiantang River-Hangzhou Bay, an important drinking water resource for cities in Yangtze River basin. Perfluorooctanoate was consistently the predominant legacy PFAS in water (8.8–130 ng/L) and sediment (3.7–49 ng/g dw). Twelve emerging PFASs were detected in water, with the dominance of 6:2 chlorinated polyfluoroalkyl ether sulfonates (6:2 Cl-PFAES; mean 11 ng/L, 0.79–57 ng/L) and 6:2 fluorotelomer sulfonate (6:2 FTS; 5.6 ng/L, < LOD–29 ng/L). Eleven emerging PFASs were found in sediment, and were also dominated by 6:2 Cl-PFAES (mean 4.3 ng/g dw, 0.19–16 ng/g dw) and 6:2 FTS (2.6 ng/g dw, < LOD–9.4 ng/g dw). Spatially, sampling sites closed to the surrounding cities had comparatively higher water concentrations of PFASs. Among emerging PFASs, 8:2 Cl-PFAES (3.0 ± 0.34) had the highest mean field-based log-transformed organic‑carbon normalized sediment-water partition coefficient (log Koc), followed by 6:2 Cl-PFAES (2.9 ± 0.35) and hexafluoropropylene oxide trimer acid (2.8 ± 0.32). p-perfluorous nonenoxybenzene sulfonate (2.3 ± 0.60) and 6:2 FTS (1.9 ± 0.54) had relatively lower mean log Koc values. To our knowledge, this is the most comprehensive study investigating the occurrence and partitioning behaviors of emerging PFASs in Qiantang River.

Emerging and Legacy Perfluoroalkyl Substances in Breastfed Chinese Infants: Renal Clearance, Body Burden, and Implications.

Human breast milk is a primary route of exposure to perfluoroalkyl substances (PFAS) in infants. To understand the associated risks, the occurrence of PFAS in human milk and the toxicokinetics of PFAS in infants need to be addressed. We determined levels of emerging and legacy PFAS in human milk and urine samples from Chinese breastfed infants, estimated renal clearance, and predicted infant serum PFAS levels. In total, human milk samples were collected from 1,151 lactating mothers in 21 cities in China. In addition, 80 paired infant cord blood and urine samples were obtained from two cities. Nine emerging PFAS and 13 legacy PFAS were analyzed in the samples using ultra high-performance liquid chromatography tandem mass spectrometry. Renal clearance rates () of PFAS were estimated in the paired samples. PFAS serum concentrations in infants ( year of age) were predicted using a first-order pharmacokinetic model. All nine emerging PFAS were detected in human milk, with the detection rates of 6:2 Cl-PFESA, PFMOAA, and PFO5DoDA all exceeding 70%. The level of 6:2 Cl-PFESA in human milk () ranked third after PFOA () and PFOS (). The estimated daily intake (EDI) values of PFOA and PFOS exceeded the reference dose (RfD) of recommended by the U.S. Environmental Protection Agency in 78% and 17% of breastfed infant samples, respectively. 6:2 Cl-PFESA had the lowest infant (), corresponding to the longest estimated half-life of 49 y. The average half-lives of PFMOAA, PFO2HxA, and PFO3OA were 0.221, 0.075, and 0.304 y, respectively. The of PFOA, PFNA, and PFDA were slower in infants than in adults. Our results demonstrate the widespread occurrence of emerging PFAS in human milk in China. The relatively high EDIs and half-lives of emerging PFAS suggest potential health risks of postnatal exposure in newborns. https://doi.org/10.1289/EHP11403.

Invited Perspective: PFAS in Breast Milk and Infant Formula-It's Time to Start Monitoring.

Invited Perspective: PFAS in Breast Milk and Infant Formula-It's Time to Start Monitoring.

Detail study on the interaction between perfluorooctanoic acid (PFOA) with human hemoglobin (Hb)

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are often referred to as legacy perfluoroalkyl substances (PFAS). Human exposure to PFAS leads to severe negative health impacts including cancers, infertility, and dysfunction in the kidneys. Steady-state absorbance, fluorescence, and circular dichroism (CD) methods were used to study the interactions between PFOA and Hb. The results demonstrate the presence of multiple PFOA binding sites on the Hb protein. The detailed analysis of the ferric hemoglobin protein (met Hb) absorbance data as a function of PFOA concentration indicates the presence of at least two binding sites with equilibrium dissociation constants of 0.8 ± (0.2) × 10−6 M and 63 ± (15) × 10−5 M. A competitive binding study with 1,8-ANS showed PFOA can bind to the same binding site as 1,8-ANS on the Hb protein. The titration curve for PFOA binding to Hb in its CO bound form (CO-Hb) yields a single equilibrium dissociation constant of 139 ± (20) × 10−6 M. PFOA binding at low concentrations occurs at the high-affinity sites leading to the destabilization of the protein structure as reflected by changes in the CD spectrum. PFOA interactions with Hb also interfere with the kinetics of CO association to this protein. The rate for CO association to Hb increases at low PFOA concentrations, whereas at elevated PFOA concentrations, the ligand association is biphasic as a new kinetic process with a different rate constant was observed. Overall, this study provides a detailed explanation of PFOA-induced structural and conformational changes to the Hb protein based on the spectroscopy data.

Experimental evidence of a limited impact of new-generation perfluoroalkyl substance C6O4 on differentiating human dopaminergic neurons from induced pluripotent stem cells.

Perfluoroalkyl substances (PFASs) are persistent pollutants, raising concerns for human health. Legacy PFAS perfluoro-octanoic acid (PFOA) accumulate in brains of people at high environmental exposure, especially in areas enriched with dopaminergic neurons (DN). In vitro exposure to 10ng/mL PFOA for 24h was also associated with an altered molecular and functional phenotype of DN differentiated from human induced pluripotent stem cells (hiPSCs). Acetic acid, 2,2-difluoro-2-((2,2,4,5-tetrafluoro-5(trifluoromethoxy)-1,3-dioxolan-4-yl)oxy)-ammonium salt (1:1), known as C6O4, is a new generation PFAS proposed to have a safer profile. Here we investigated the effect of C6O4 exposure on the molecular phenotype of hiPSC-derived DN. Cells were exposed to C6O4 for 24h, at the concentration of 10ng/mL, at neuronal commitment (DP1), neuronal precursor (DP2) and the mature dopaminergic (DP3) phases of differentiation. Liquid-chromatography/mass-spectrometry showed negligible cell accumulation of C6O4 at each differentiation stage and by staining with Merocyanine-540 we observed unaltered cell membrane fluidity. Immunofluorescence showed that the expression of tyrosine hydroxylase (TH) and βIII-Tubulin was unaffected by the exposure to C6O4 at each differentiation phase (respectively: DP1, p=0.332; DP2, p=0.623; DP3, p=0.816, with respect to control unexposed conditions). Exposure to C6O4 is presumed to have minor effects on cell molecular/functional phenotype of developing human DN cells, requiring confirm on in vivo models.

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.

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.

Boron-doped diamond electrodes degrade short- and long-chain per- and polyfluorinated alkyl substances in real industrial wastewaters

Electrochemical oxidation (ECO) with boron-doped diamond (BDD) electrode of six legacy perfluoroalkyl substances (PFAS) present in semiconductor fabrication wastewaters was investigated in single-solutes, multi-solutes, and real wastewater matrices. ECO degradation kinetics decreased as carbon length decreased in single-solute systems. Because heterogeneous catalysis involves PFAS interacting at the electrode surface, the impact of PFAS in solution on altering the potential affinity for PFAS itself on the surface was quantified. The BDD electrode surface wettability, defined by the surface contact angle, increased with longer chain length and diminished with increasing PFAS concentration. PFASs with a sulfonated head group degraded 2–3x faster than their carboxylic counterparts. Industrial wastewaters can have high background organic concentrations and have a large pH range prior to discharge, offering different opportunities to treat for PFAS near the semiconductor manufacturing tool or prior to pH adjustment and discharge to sanitary sewers. Increasing pH (up to 12) decreased the evolution of reactive oxygen species on the electrode surface and therefore decreased removal kinetics compared to pH 3 and 7. The presence of surfactants (tetramethylammonium hydroxide [TMAH] and sodium dodecyl sulfonate [SDS]) in the wastewater significantly reduced the degradation efficiency of ECO. However, compared to single-solute PFAS systems, multi-solute solutions (mixture of 6 PFASs) had higher degradation rates during ECO. In a real wastewater (originated from RO concentrate), PFASs were efficiently removed in ~320 min reaction time. These results demonstrated the promise for ECO to treat PFAS contained in industrial manufacturing processes at both tool level and blended wastewater.

Maternal Levels of Perfluoroalkyl Substances (PFAS) during Early Pregnancy in Relation to Preeclampsia Subtypes and Biomarkers of Preeclampsia Risk.

Background:Prenatal exposure to perfluoroalkyl substances (PFAS) has been previously associated with preeclampsia, although findings are mixed with respect to the direction and magnitude of effect. To our knowledge, no studies have examined associations between PFAS and preeclampsia subtypes, which may have distinct etiologies.Objective:We examined associations between PFAS, any preeclampsia diagnosis, and early- and late-onset preeclampsia. In addition, we estimated associations between PFAS and the angiogenic biomarkers soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF), which provide an estimate of pro- and anti-angiogenic activity within the placenta.Methods:This case–control study ( cases, controls) was sampled from the LIFECODES birth cohort. Nine legacy PFAS were quantified in maternal plasma from early pregnancy ( 10 wk) and angiogenic biomarkers were quantified in maternal plasma from four study visits ( 10, 18, 26, and 35 wk). Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the association between an interquartile range (IQR)-increase in PFAS and preeclampsia outcomes. Linear regression was used to estimate associations between an IQR-increase in PFAS and concentrations of angiogenic biomarkers.Results:Both perfluorodecanoic acid ( 1.64, 95% CI: 1.08, 2.47) and perfluorooctanesulfonic acid ( 1.60, 95% CI: 1.06, 2.43) were associated with higher odds of late-onset preeclampsia. Associations tended to be below the null for early-onset preeclampsia, although findings were imprecise. Few associations were noted between PFAS and angiogenic biomarkers.Discussion:Maternal PFAS concentrations were associated with higher odds of late-onset preeclampsia. Heterogeneity of preeclampsia should be considered in future studies because populations may have different distributions of disease subtypes. https://doi.org/10.1289/EHP9091

Maternal levels of perfluoroalkyl substances (PFAS) during early pregnancy in relation to preeclampsia subtypes

BACKGROUND AND AIM: Prenatal exposure to perfluoroalkyl substances (PFAS) has been previously associated with preeclampsia, although findings are mixed. However, no studies have examined associations between PFAS and preeclampsia subtypes, which may have distinct etiologies. Thus, we examined associations between PFAS and individual preeclampsia subtypes (i.e. early- and late-onset) using both single- and multi-pollutant approaches. METHODS: This case-control study (n = 75 cases, n = 75 controls) was sampled from the prospective LIFECODES birth cohort. Within the sample of preeclampsia cases, 21 were defined as early-onset ( 34 weeks gestation) and 54 were defined as late-onset (≥ 34 weeks). Nine legacy PFAS were quantified in maternal plasma from early pregnancy (median 10 weeks). As a single-pollutant approach, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) of the association between an interquartile range (IQR)-increase in PFAS and preeclampsia subtypes. As a multi-pollutant approach, we used quantile g-computation to estimate the joint association of PFAS with preeclampsia subtypes. RESULTS:After adjusting for potential confounders, both perfluorodecanoic acid (PFDA; OR: 1.76, 95% CI: 1.07, 2.91) and perfluorooctane sulfonic acid (PFOS; OR: 2.29, 95% CI: 1.21, 4.35) were associated with higher odds of late-onset preeclampsia. Using quantile g-computation, a simultaneous one-quartile increase in all PFAS was also associated with higher odds of late-onset preeclampsia (OR: 2.28, 95% CI: 1.12, 4.64). Individual and joint associations between PFAS and early-onset preeclampsia were null, as were associations with overall preeclampsia diagnosis. CONCLUSIONS:Maternal PFAS concentrations were associated with odds of late-onset preeclampsia, though associations were null for early-onset preeclampsia. These findings suggest that PFAS exposure may be more closely associated with late-onset preeclampsia and warrant further study. In addition, heterogeneity of preeclampsia should be considered in future studies as populations may have different distributions of disease subtypes. KEYWORDS: PFAS, Pregnancy outcomes, Mixtures

Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence.

Polyfluoro- and perfluoro–alkyl substances (PFAS) are organic chemicals extensively used worldwide for industry and consumer products. Due to their chemical stability, PFAS represent a major cause of environmental pollution. PFAS accumulate in animal and human blood and tissues exerting their toxicity. We performed a review of the epidemiological studies exploring the relationship between exposure to PFAS and thromboembolic cardiovascular disease. An increase in cardiovascular disease or death related to PFAS exposure has been reported from cross-sectional and longitudinal observational studies with evidence concerning the relation with early vascular lesions and atherosclerosis. Several studies indicate an alteration in lipid and glucose metabolism disorders and increased blood pressure as a possible link with cardiovascular thromboembolic events. We also examined the recent evidence indicating that legacy and new PFAS can be incorporated in platelet cell membranes giving a solid rationale to the observed increase risk of cardiovascular events in the populations exposed to PFAS by directly promoting thrombus formation. Exposure to PFAS has been related to altered plasma membrane fluidity and associated with altered calcium signal and increased platelet response to agonists, both in vitro and ex vivo in subjects exposed to PFAS. All the functional responses are increased in platelets by incorporation of PFAS: adhesion, aggregation, microvesicles release and experimental thrombus formation. These findings offer mechanistic support the hypothesis that platelet-centred mechanisms may be implicated in the increase in cardiovascular events observed in populations chronically exposed to PFAS.

Levels, distributions, and sources of legacy and novel per- and perfluoroalkyl substances (PFAS) in the topsoil of Tianjin, China

Soil is a major sink for per- and perfluoroalkyl substances (PFAS), wherein PFAS may be transferred through the food chain to predators at upper trophic levels, which poses a threat to human health. Herein, the concentrations and distributions of legacy and novel PFAS in topsoil samples from different functional areas in Tianjin were comprehensively investigated. Seventeen PFAS congeners were identified, with concentrations ranging from 0.21 ng/g to 5.35 ng/g, with a mean concentration of 1.25 ng/g. The main PFAS in the topsoil was perfluorooctanoic acid (PFOA). 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA; <MDL–1.95 ng/g, mean 0.11 ng/g), as an emerging substitute for perfluorooctane sulfonate (PFOS), was also detected in the topsoil. It showed slightly higher concentrations than PFOS (<MDL–1.62 ng/g, mean 0.10 ng/g), indicating it has gradually replaced legacy PFOS in this area. Based on the positive-definite matrix factor (PMF) receptor model, the major PFAS sources was dominated by textile treatment, metal electroplating plants, and some potential precursors of PFAS with longer chains (>C8) were the major sources (43.4%), followed by food packaging as well as coating materials (25.5%). In addition, Spearman correlation analysis and the structural equation model showed that population density significantly impacted the PFAS distribution in the topsoil of Tianjin.

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.