Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence. METHODS: This research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003-2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis. RESULTS: Higher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98). CONCLUSIONS: This study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

PFAS Contamination in Europe: Generating Knowledge and Mapping Known and Likely Contamination with "Expert-Reviewed" Journalism.

While the extent of environmental contamination by per- and polyfluoroalkyl substances (PFAS) has mobilized considerable efforts around the globe in recent years, publicly available data on PFAS in Europe were very limited. In an unprecedented experiment of "expert-reviewed journalism" involving 29 journalists and seven scientific advisers, a cross-border collaborative project, the "Forever Pollution Project" (FPP), drew on both scientific methods and investigative journalism techniques such as open-source intelligence (OSINT) and freedom of information (FOI) requests to map contamination across Europe, making public data that previously had existed as "unseen science". The FPP identified 22,934 known contamination sites, including 20 PFAS manufacturing facilities, and 21,426 "presumptive contamination sites", including 13,745 sites presumably contaminated with fluorinated aqueous film-forming foam (AFFF) discharge, 2911 industrial facilities, and 4752 sites related to PFAS-containing waste. Additionally, the FPP identified 231 "known PFAS users", a new category for sites with an intermediate level of evidence of PFAS use and considered likely to be contamination sources. However, the true extent of contamination in Europe remains significantly underestimated due to a lack of comprehensive geolocation, sampling, and publicly available data. This model of knowledge production and dissemination offers lessons for researchers, policymakers, and journalists about cross-field collaborations and data transparency.

Development of ionic-liquid-impregnated activated carbon for sorptive removal of PFAS in drinking water treatment.

Adsorption of per- and poly-fluoroalkyl substances (PFAS) on activated carbon (AC) is considerably hindered by the surface water constituents, degrading the ability of the AC adsorption process to remove PFAS in drinking water treatment. Herein, we developed ionic-liquid-impregnated AC (IL/AC) as an alternative to AC for PFAS sorption and demonstrated its performance with real surface water for the first time. Ionic liquids (ILs) of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (IL(C2)) and 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (IL(C6)) were selected from among 272 different ILs using the conductor-like screening model for realistic solvents (COSMO-RS) simulation. Impregnation of the ILs in AC was verified using various analytical techniques. Although the synthesized IL/ACs were less effective than pristine AC in treating PFAS in deionized water, their performances were less impacted by the surface water constituents, resulting in comparable or sometimes better performances than pristine AC for treating PFAS in surface water. The removal efficiencies of 10 wt% IL(C6)/AC for six PFAS were 1.40-1.96 times higher than those of pristine AC in a surface water sample containing 2.6 mg/L dissolved organic carbon and millimolar-level divalent cation concentration. PFAS partitioning from the surface water to ILs was not hindered by dissolved organic matter and was enhanced by the divalent cations, indicating the advantages of IL/ACs for treating significant amounts of PFAS in water. The synthesized IL/ACs were effective at treating coexisting pharmaceutical and personal-care products in surface water, showcasing their versatility for treating a broad range of water micropollutants.

Association of per- and polyfluoroalkyl substances with constipation: The National Health and Nutrition Examination Survey (2005-2010).

BACKGROUND: The impact of per- and polyfluoroalkyl substances (PFAS) on constipation, as mediated through gastrointestinal absorption and perturbations to the intestinal microecology, remains poorly understood. OBJECTIVE: This study seeks to explain the relationship between PFAS and constipation. METHODS: A total of 2945 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were included in this study. Constipation was defined using the Bristol Stool Form Scale (BSFS) based on stool consistency. The relationship between PFAS and constipation was evaluated using weighted logistic regression and restricted cubic spline (RCS) analysis, while adjusting for confounding variables. RESULTS: The weighted median concentration of total PFAS (ΣPFAS) was significantly lower in individuals with constipation (19.01 µg/L) compared to those without constipation (23.30 µg/L) (p < 0.0001). Subgroup analysis revealed that the cumulative effect of PFAS was more pronounced in the elderly, men, individuals with obesity, high school education or equivalent, and high-income individuals (p < 0.05). After adjusting for confounding factors, multivariable analysis demonstrated an inverse association between PFOA [OR (95% CI), 0.666(0.486,0.914)] and PFHxS [OR (95% CI), 0.699(0.482,1.015)], and constipation. None of the personal and lifestyle factors showed a significant correlation with this negative association, as confirmed by subgroup analysis and interaction testing (p for interaction > 0.05). The RCS analysis demonstrated a linear inverse relationship between PFAS levels and constipation. CONCLUSION: The findings of this study provide evidence of a significant inverse correlation between serum concentrations of PFAS, particularly PFOA and PFHxS, and constipation.

Evolutionary obstacles and not C-F bond strength make PFAS persistent.

The fate of organic matter in the environment, including anthropogenic chemicals, is largely predicated on the enzymatic capabilities of microorganisms. Microbes readily degrade, and thus recycle, most of the ~100,000 commercial chemicals used in modern society. Per- and polyfluorinated compounds (PFAS) are different. Many research papers posit that the general resistance of PFAS to microbial degradation is based in chemistry and that argument relates to the strength of the C-F bond. Here, I advance the opinion that the low biodegradability of PFAS is best formulated as a biological optimization problem, hence evolution. The framing of the problem is important. If it is framed around C-F bond strength, the major effort should focus on finding and engineering new C-F cleaving enzymes. The alternative, and preferred approach suggested here, is to focus on the directed evolution of biological systems containing known C-F cleaving systems. There are now reports of bacteria degrading and/or growing on multiply fluorinated arenes, alkenoic and alkanoic acids. The impediment to more efficient and widespread biodegradation in these systems is biological, not chemical. The rationale for this argument is made in the five sections below that follow the Introduction.

On the Feasibility of Rugose Lipid Microparticles in Pressurized Metered Dose Inhalers with Established and New Propellants.

Pressurized metered dose inhalers (pMDIs) require optimized formulations to provide stable, consistent lung delivery. This study investigates the feasibility of novel rugose lipid particles (RLPs) as potential drug carriers in pMDI formulations. The physical stability of RLPs was assessed in three different propellants: the established HFA-134a and HFA-227ea and the new low global-warming-potential (GWP) propellant HFO-1234ze. A feedstock containing DSPC and calcium chloride was prepared without pore forming agent to spray dry two RLP batches at inlet temperatures of 55 °C (RLP55) and 75 °C (RLP75). RLPs performance in pMDI formulations was compared to two reference samples that exhibit significantly different performance when suspended in propellants: well-established engineered porous particles and particles containing 80% trehalose and 20% leucine (80T20L). An accelerated stability study at 40 °C and relative humidity of 7% ± 5% was conducted over 3 months. At different time points, a shadowgraphic imaging technique was used to evaluate the colloidal stability of particles in pMDIs. Field emission electron microscopy with energy dispersive X-ray spectroscopy was used to evaluate the morphology and elemental composition of particles extracted from the pMDIs. After 2 weeks, all 80T20L formulations rapidly aggregated upon agitation and exhibited significantly inferior colloidal stability compared to the other samples. In comparison, both the RLP55 and RLP75 formulations, regardless of the propellant used, retained their rugose structure and demonstrated excellent suspension stability comparable with the engineered porous particles. The studied RLPs demonstrate great potential for use in pMDI formulations with HFA propellants and the next-generation low-GWP propellant HFO-1234ze.

Investigating the sources and fate of per- and polyfluoroalkyl substances (PFAS) in food waste compost.

Composting municipal food waste is a key strategy for beneficially reusing methane-producing waste that would otherwise occupy landfill space. However, land-applied compost can cycle per- and polyfluoroalkyl substances (PFAS) back into the food supply and the environment. We partnered with a pilot-scale windrow composting facility to investigate the sources and fate of 40 PFAS in food waste compost. A comparison of feedstock materials yielded concentrations of ∑PFAS under 1 ng g-1 in mulch and food waste and at 1380 ng g-1 in leachate from used compostable food contact materials. Concentrations of targeted ∑PFAS increased with compost maturity along the windrow (1.85-23.1 ng g-1) and in mature stockpiles of increasing curing age (12.6-84.3 ng g-1). Among 15 PFAS quantified in compost, short-chain perfluorocarboxylic acids (PFCAs) - C5 and C6 PFCAs in particular - led the increasing trend, suggesting biotransformation of precursor PFAS into these terminal PFAS through aerobic decomposition. Several precursor PFAS were also measured, including fluorotelomer carboxylic acids (FTCAs) and polyfluorinated phosphate diesters (PAPs). However, since most targeted analytical methods and proposed regulations prioritize terminal PFAS, testing fully matured compost would provide the most relevant snapshot of PFAS that could be land applied. In addition, removing co-disposed food contact materials from the FW feedstock onsite yielded only a 37 % reduction of PFAS loads in subsequent compost, likely due to PFAS leaching during co-disposal. Source-separation of food contact materials is currently the best management practice for meaningful reduction of PFAS in food waste composts intended for land application.

Poly- and perfluoroalkyl substances (PFASs) in amphibians and reptiles - exposure and health effects.

Poly- and perfluoroalkyl substances (PFASs) are commonly used in various industries and everyday products, including clothing, electronics, furniture, paints, and many others. PFASs are primarily found in aquatic environments, but also present in soil, air and plants, making them one of the most important and dangerous pollutants of the natural environment. PFASs bioaccumulate in living organisms and are especially dangerous to aquatic and semi-aquatic animals. As endocrine disruptors, PFASs affect many internal organs and systems, including reproductive, endocrine, nervous, cardiovascular, and immune systems. This manuscript represents the first comprehensive review exclusively focusing on PFASs in amphibians and reptiles. Both groups of animals are highly vulnerable to PFASs in the natural habitats. Amphibians and reptiles, renowned for their sensitivity to environmental changes, are often used as crucial bioindicators to monitor ecosystem health and environmental pollution levels. Furthermore, the decline in amphibian and reptile populations worldwide may be related to increasing environmental pollution. Therefore, studies investigating the exposure of amphibians and reptiles to PFASs, as well as their impacts on these organisms are essential in modern toxicology. Summarizing the current knowledge on PFASs in amphibians and reptiles in a single manuscript will facilitate the exploration of new research topics in this field. Such a comprehensive review will aid researchers in understanding the implications of PFASs exposure on amphibians and reptiles, guiding future investigations to mitigate their adverse effects of these vital components of ecosystems.

Per- and polyfluoroalkyls used as cosmetic ingredients - Qualitative study of 765 cosmetic products.

Per- and polyfluoroalkyl substances (PFAS) form a vast family comprising more than 4700 synthetic compounds. Their molecules contain a terminal functional group and a hydrophobic carbon tail (alkyl group) at which the hydrogen atoms are totally (in the case of perfluorinated compounds) or partially (in the case of polyfluorinated compounds) replaced by fluorine atoms. Due to the very specific properties of their structure, they have been used in a vast range of applications over the last 70 years. These substances are considered to be of concern for the environment. Their effects on human health are still poorly understood because studies are still too rare, but the cutaneous route could be a significant pathway of penetration. In this context, we made a qualitative study to assess the presence of PFAS in various cosmetics such as hygiene products, skin care products, make-up and perfumes. Among the 765 products studied, we found 11 different PFAS. Polytetrafluoroethylene (PTFE) and perfluorodecalin, present in 25.9% and 22.2% of products containing it, respectively, were the most frequent. Although the presence of this type of ingredient seems to be limited in Europe, make-up appears to be the type of product most likely to contain PFAS.

A complementary method with PFBBr-derivatization based on a GC-EI-MS platform for the simultaneous quantitation of short-, medium- and long-chain fatty acids in murine plasma and feces samples.

Fatty acids (FAs) are essential molecules in all organisms and are involved in various physiological and pathophysiological processes. Pentafluorobenzyl bromide (PFBBr) is commonly used for FA derivatization for gas chromatography-mass spectrometry (GC-MS) quantification by chemical ionization (CI). While CI is the conventional ionization mode for PFBBr derivatization, the electron ionization (EI) source has also demonstrated efficacy in achieving satisfactory analytical performance for the analysis of PFB esters. In this study, we present a novel approach utilizing PFBBr-derivatization on a GC-EI-MS platform to quantitatively analyze a comprehensive range of 44 fatty acids (FAs) spanning from C2 to C24. The method's sensitivity, precision, accuracy, linearity, recovery, and matrix effect were rigorously validated against predetermined acceptance criteria. In comparison to the conventional CI ionization mode, the utilization of PFBBr-derivatization in GC-EI-MS exhibits a wider range of applications and achieves comparable sensitivity levels to the conventional CI platform. By using this method, we successfully quantified 44 FAs in plasma and feces samples from the mice with deoxynivalenol (DON)-induced kidney injury. Among these, the levels of most FA species were increased in the DON-exposure group compared with the control group. The orthogonal partial least squares discriminant analysis (OPLS-DA) of all the tested FAs showed a visual separation of the two groups, indicating DON exposure resulted in a disturbance of the FA profile in mice. These results indicate that the established method by integration of GC-MS with PFBBr derivatization is an efficient approach to quantify the comprehensive FA profile, which includes short-, medium- and long-chain FAs. In addition, our study provides new insights into the mechanism underlying DON exposure-induced kidney injury.

All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980-2018).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. METHODS: The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20-84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. RESULTS: During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107-109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. CONCLUSIONS: For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Association of exposure to multiple perfluoroalkyl and polyfluoroalkyl substances and glucose metabolism in National Health and Nutrition Examination Survey 2017-2018.

Objective: To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism. Results: The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend (p < 0.001), whereas insulin levels demonstrated a downward linear trend (p = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: ß = 0.059, p < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin ß = -0.194, p < 0.001, HOMA-IR ß = -0.132, p = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin ß = 0.191, p = 0.018, HOMA-IR ß = 0.220, p = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS. Conclusion: Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms.

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-(hCGα) and beta-subunits (hCGß), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS: Perfluorohexane sulfonic acid (PFHxS) [hCGß: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGß. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGß only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGß only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGß differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

Peril in the Pipeline: Unraveling the threads of PFAS contamination in U.S. drinking water systems.

We examined the spatial distribution of Per- and Polyfluoroalkyl Substances (PFAS) in the US drinking water and explored the relationship between PFAS contamination, public water systems (PWS) characteristics, and socioeconomic attributes of the affected communities. Using data from the EPA's third Unregulated Contaminant Rule, the Census Bureau, and the Bureau of Labor Statistics, we identified spatial contamination hot spots and found that PFAS contamination was correlated with PWSs size, non-surface raw water intake sources, population, and housing density. We also found that non-white communities had less PFAS in drinking water. Lastly, we observed that PFAS contamination varied depending on regional industrial composition. The results showed that drinking water PFAS contamination was an externality of not only some industrial activities but also household consumption.

Lactational exposure to perfluorooctane sulfonate remains a potential risk in brain function of middle-aged male mice.

Perfluorooctane sulfonate (PFOS) exerts adverse effects on neuronal development in young population. Limited evidences have shown that early-life PFOS exposure holds a potential risk for developing age-related neurodegenerative diseases such as Alzheimer's disease later in life. The present study investigated the effects of lactational PFOS exposure on cognitive function using one-year-old mice. Dams were exposed to PFOS (1 mg/kg body weight) through lactation by gavage. Male offspring were used for the behavior test battery to assess cognitive function. Western blot analysis was conducted to measure the levels of proteins related to the pathogenesis of Alzheimer's disease. PFOS-exposed mice displayed a mild deficiency in social recognition. In the hippocampus, the expression of tau protein was significantly increased. These results underline a mild effect of developing PFOS exposure on cognitive function and neurodegeneration. The present study presents the long-lasting effects of PFOS in middle-aged period and warrants a potential aftermath.

Fate of perfluoroalkyl and polyfluoroalkyl substances (PFAS) through two full-scale wastewater sludge incinerators.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are an emerging issue in wastewater treatment. High-temperature thermal processes, incineration being time-tested, offer the opportunity to destroy and change the composition of PFAS. The fate of PFAS has been documented through wastewater sludge incinerators, including a multiple hearth furnace (MHF) and a fluidized bed furnace (FBF). The dewatered wastewater sludge feedstock averaged 247- and 1280-µmol targeted PFAS per sample run in MHF and FBF feed, respectively. Stack emissions (reportable for all targeted PFAS from MHF only) averaged 5% of that value with shorter alkyl chain compounds comprising the majority of the targeted PFAS. Wet scrubber water streams accumulated nonpolar fluorinated organics from the furnace exhaust with an average of 0.740- and 0.114-mol F- per sample run, for the MHF and FBF, respectively. Simple alkane PFAS measured at the stack represented 0.5%-4.5% of the total estimated facility greenhouse gas emissions. PRACTITIONER POINTS: The MHF emitted six short chain PFAS from the stack, which were shorter alkyl chain compounds compared with sludge PFAS. The FBF did not consistently emit reportable PFAS from the stack, but contamination complicated the assessment. Five percent of the MHF sludge molar PFAS load was reported in the stack. MHF and FBF wet scrubber water streams accumulated nonpolar fluorinated organics from the furnace exhaust. Ultra-short volatile alkane PFAS measured at the stack represented 0.5%-4.5% of the estimated facility greenhouse gas emissions.

Perfluorooctanoic acid induces cardiac dysfunction in human induced pluripotent stem cell-derived cardiomyocytes.

Perfluorooctanoic acid (PFOA), commonly found in drinking water, leads to widespread exposure through skin contact, inhalation, and ingestion, resulting in detectable levels of PFOA in the bloodstream. In this study, we found that exposure to PFOA disrupts cardiac function in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed reductions in field and action potentials in hiPSC-CMs exposed to PFOA. Furthermore, PFOA demonstrated a dose-dependent inhibitory effect on various ion channels, including the calcium, sodium, and potassium channels. Additionally, we noted dose-dependent inhibition of the expression of these ion channels in hiPSC-CMs following exposure to PFOA. These findings suggest that PFOA exposure can impair cardiac ion channel function and decrease the transcription of genes associated with these channels, potentially contributing to cardiac dysfunction such as arrhythmias. Our study sheds light on the electrophysiological and epigenetic consequences of PFOA-induced cardiac dysfunction, underscoring the importance of further research on the cardiovascular effects of perfluorinated compounds (PFCs).

Per- and polyfluoroalkyl substances inhibit human and rat 17ß-hydroxysteroid dehydrogenase 1: Quantitative structure-activity relationship and molecular docking analysis.

Per- and polyfluoroalkyl (PFAS) substances are enduring industrial materials. 17ß-Hydroxysteroid dehydrogenase isoform 1 (17ß-HSD1) is an estrogen metabolizing enzyme, which transforms estrone into estradiol in human placenta and rat ovary. Whether PFAS inhibit 17ß-HSD1 and what the structure-activity relationship (SAR) remains unexplored. We screened 18 PFAS for inhibiting human and rat 17ß-HSD1 in microsomes and studied their SAR and mode of action(MOA). Of the 11 perfluorocarboxylic acids (PFCAs), C8-C14 PFCAs at a concentration of 100 µM substantially inhibited human 17ß-HSD1, with order of C11 (half-maximal inhibition concentration, IC50, 8.94 µM) > C10 (10.52 µM) > C12 (14.90 µM) > C13 (30.97 µM) > C9 (43.20 µM) > C14 (44.83 µM) > C8 (73.38 µM) > others. Of the 7 per- and poly-fluorosulfonic acids (PFSAs), the potency was C8S (IC50, 14.93 µM) > C7S (80.70 µM) > C6S (177.80 µM) > others. Of the PFCAs, C8-C14 PFCAs at 100 µM markedly reduced rat 17ß-HSD1 activity, with order of C11 (IC50, 9.11 µM) > C12 (14.30 µM) > C10 (18.24 µM) > C13 (25.61 µM) > C9 (67.96 µM) > C8 (204.39 µM) > others. Of the PFSAs, the potency was C8S (IC50, 37.19 µM) > C7S (49.38 µM) > others. In contrast to PFOS (C6S), the partially fluorinated compound 6:2 FTS with an equivalent number of carbon atoms demonstrated no inhibition of human and rat 17ß-HSD1 activity at a concentration of 100 µM. The inhibition of human and rat enzymes by PFAS followed a V-shaped trend from C4 to C14, with a nadir at C11. Moreover, human 17ß-HSD1 was more sensitive than rat enzyme. PFAS inhibited human and rat 17ß-HSD1 in a mixed mode. Docking analysis revealed that they bind to the NADPH and steroid binding site of both 17ß-HSD1 enzymes. The 3D quantitative SAR (3D-QSAR) showed that hydrophobic region, hydrogen bond acceptor and donor are key factors in binding to 17ß-HSD1 active sites. In conclusion, PFAS exhibit inhibitory effects on human and rat 17ß-HSD1 depending on factors such as carbon chain length, degree of fluorination, and the presence of carboxylic acid or sulfonic acid groups, with a notable V-shaped shift observed at C11.

Knock-in mutagenesis in Drosophila Rdl underscores the critical role of the conserved M3 glycine in mediating the actions of broflanilide and isocycloseram on GABA receptors.

γ-Aminobutyric acid receptors (GABARs) are crucial targets for pest control chemicals, including meta-diamide and isoxazoline insecticides, which act as negative allosteric modulators of insect GABARs. Previous cell-based assays have indicated that amino acid residues in the transmembrane cavity between adjacent subunits of Drosophila RDL GABAR (i.e., Ile276, Leu280, and Gly335) are involved in mediating the action of meta-diamides. In this study, to confirm this result at the organismal level, we employed CRISPR/Cas9-mediated genome editing, generated six transgenic Drosophila strains carrying substitutions in these amino acid residues, and investigated their sensitivity to broflanilide and isocycloseram. Flies homozygous for the I276F mutation did not exhibit any change in sensitivity to the tested insecticides compared to the control flies. Conversely, I276C homozygosity was lethal, and heterozygous flies exhibited ∼2-fold lower sensitivity to broflanilide than the control flies. Flies homozygous for the L280C mutation survived into adulthood but exhibited infertility. Both heterozygous and homozygous L280C flies exhibited ∼3- and âˆ¼20-fold lower sensitivities to broflanilide and isocycloseram, respectively, than the control flies. The reduction in sensitivity to isocycloseram in L280C flies diminished to ∼3-fold when treated with piperonyl butoxide. Flies homozygous for the G335A mutation reached the adult stage. However, they were sterile, had small bodies, and exhibited reduced locomotion, indicating the critical role of Gly335 in RDL function. These flies exhibited markedly increased tolerance to topically applied broflanilide and isocycloseram, demonstrating that the conserved Gly335 is the target of the insecticidal actions of broflanilide and isocycloseram. Considering the significant fitness costs, the Gly335 mutation may not pose a serious risk for the development of resistance in field populations of insect pests. However, more careful studies using insect pests are needed to investigate whether our perspective applies to resistance development under field conditions.

Novel Meta-Diamide Compounds Containing Sulfide Derivatives Were Designed and Synthesized as Potential Pesticides.

The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A-D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L-1. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00-100.00% insecticidal activity even at a concentration as low as 0.625 mg·L-1. As determined by structure-activity relationship (SAR) analysis, compounds with R1 = CH3 and R2 = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L-1, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds.