Stormwater runoff is a significant contributor of phosphorus (P) loading to waterbodies around the world. Green stormwater infrastructure (GSI) that uses filtration media, such as bioretention, can effectively retain suspended solids and associated particulate P, but is commonly less effective for soluble P retention. The addition of aluminum-based drinking water treatment residuals (DWTRs) may increase P-sorbing capacity of GSI media, though guidance is needed for material selection and to reduce risk of potential contamination. This study examined the P removal capacities of DWTRs (n = 11) from drinking water treatment plants in the New England region (northeastern USA). DWTRs were compared for P-sorption potential using batch isotherm and column experiments and characterized for several material properties as well as arsenic leaching and per and polyfluoroalkyl substances (PFAS) content. Results indicate that P retention capacity of DWTRs is generally high (>1,000 mg P kg(-1)) but varies by approximately one order of magnitude. Lower DWTR bulk density and greater oxalate-extractable Al + Fe were correlated with greater P retention in column experiments. Our findings also indicate that the potential for significant arsenic leaching is low. PFAS were detected in 36% of DWTRs, often at low levels near the method detection limit, with three DWTRs having higher levels of certain PFAS. The addition of DWTRs to GSI is promising for enhanced soluble P removal on a decadal scale (10-90 years), but additional research on As, PFAS, and other contaminants should be pursued prior to use, especially in areas with known or suspected source water contamination. Achieving effective long-term P removal requires selecting DWTRs with favorable material properties (e.g., drier, lower bulk density, greater oxalate-extractable Al + Fe), and mixture with sand at up to 10% DWTR by volume and potentially higher if proven to not impede hydraulic conductivity. Field monitoring of DWTR-enhanced infrastructure at multiple time points postinstallation (e.g., years 1, 5, 10, 20, and 30) is needed to confirm P removal longevity over expected infrastructure lifespans.

Per- and polyfluoroalkyl substances (PFAS) are a class of man-made persistent chemicals that have been detected in both terrestrial and aquatic environments and thus impact humans, household pets, agricultural species, and wildlife. PFAS exposure is linked to a variety of adverse health consequences, including cancer and immune disruption. This study investigates differences in PFAS exposure between California (CSL, n = 69) and Galapagos (GSL, n = 65) sea lion pups and juveniles across various sampling locations within each species' habitat range. Whereas the GSL were all considered healthy, 17 of the 69 CSL were classified as malnourished. Comparing the two species, significantly higher serum concentrations of summed PFAS, perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were detected in CSL than in GSL. This elevated PFAS exposure in CSL is likely related to historic pollution in their environment and close proximity to the urbanized coastline of Southern California. Within species, malnourished CSL had significantly higher PFNA than healthy CSL pups. GSL pups also tended to have higher PFAS levels than GSL juveniles. Within the Galapagos archipelago, PFAS exposure differed between rookeries, with PFOS exceeding its method reporting limit (0.5 ng/mL) in every sample, including GSL from islands uninhabited by humans. Summed PFAS, PFNA, PFDA, and perfluoroundecanoic acid (PFUnA) were all significantly higher in sea lions sampled on uninhabited than inhabited islands in the Galapagos archipelago. This study is the first comprehensive report of PFAS in CSL and the first archipelago-wide assessment of PFAS in GSL.

Non-targeted analysis (NTA) using high-resolution mass spectrometry without defined chemical targets has the potential to expand and improve chemical monitoring in many fields. Despite rapid advancements within the research community, NTA methods and data remain underutilized by many potential beneficiaries. To better understand barriers toward widespread adoption, the Best Practices for Non-Targeted Analysis (BP4NTA) working group conducted focus group meetings and follow-up surveys with scientists (n = 61) from various sectors (e.g., drinking water utilities, epidemiologists, n = 9) where NTA is expected to provide future value. Meeting participants included producers and end-users of NTA data with a wide range of familiarity with NTA methods and outputs. Discussions focused on identifying specific barriers that limit adoption and on setting NTA product development priorities. Stated priorities fell into four major categories: 1) education and training materials; 2) QA/QC frameworks and study design guidance; 3) accessible compound databases and libraries; and 4) NTA data linkages with chemical fate and toxicity information. Based on participant feedback, this manuscript proposes research directions, such as standardization of training materials, that BP4NTA and other institutions can pursue to expand NTA use in various application scenarios and decision contexts.

Non-targeted analysis (NTA) is commonly used for the detection and identification of emerging pollutants, including many per- and polyfluoroalkyl substances (PFAS). While NTA outputs are often non-quantitative, concentration estimation is now possible using quantitative non-targeted analysis (qNTA) approaches. To date, few studies have examined matrix effects on qNTA performance, and little is therefore known about the implications of matrix effects on qNTA results and interpretations. Using a set of 19 PFAS, we examined the impacts of drinking water (DW) and waste-activated sludge matrices on qNTA performance across three qNTA approaches: one structure-independent approach based on “global” surrogates and two structure-dependent approaches based on “expert-selected” surrogates and predicted ionization efficiency (IE) regression. The performance of each qNTA approach was examined separately for the PFAS prepared in pure solvent, DW extract, and sludge extract using leave-one-out modeling. Performance was evaluated using previously defined qNTA metrics that describe predictive accuracy, uncertainty, and reliability. The studied sample matrices had minimal effects on qNTA accuracy and larger effects on qNTA uncertainty and reliability. Using solvent-based surrogate data to inform matrix-based estimations yielded lower uncertainty, but also lower reliability, emphasizing that uncertainty must be considered in context of reliability. No single qNTA approach uniformly performed best across all comparisons. Since the IE regression and global surrogates approaches proved most reliable, we recommended them for future qNTA applications. This study highlights the importance of examining multiple performance metrics and utilizing matrix-matched surrogate data in qNTA studies.

The US Environmental Protection Agency (EPA) uses non-targeted analysis (NTA) to characterize potential risks associated with environmental pollutants and anthropogenic materials. NTA is used throughout EPA’s Office of Research and Development (ORD) to support the needs of states, tribes, EPA regions, EPA program offices, and other outside partners. NTA methods are complex and conducted via myriad instrumental platforms and software products. Comprehensive standards do not yet exist to guide NTA quality assurance/quality control (QA/QC) procedures. Furthermore, no single software tool meets EPA’s needs for QA/QC review and documentation. Considering these factors, ORD developed “INTERPRET NTA” (Interface for Processing, Reviewing, and Translating NTA data) to support liquid chromatography (LC) high-resolution mass spectrometry (HRMS) NTA experiments. For purposes of NTA QA/QC, INTERPRET NTA (1) calculates data quality statistics related to accuracy, precision, and reproducibility; (2) produces interactive visualizations to facilitate quality threshold optimization; and (3) outputs comprehensive documentation for inclusion in official reports and research publications. INTERPRET NTA has additional functionality to facilitate rapid chemical identification and risk-based prioritization. The current article describes only the QA/QC elements of INTERPRET NTA’s MS1 workflow, which are demonstrated using published data from a de facto water reuse study. INTERPRET NTA, in its current form, exists primarily to meet the needs of EPA and its partners, but a public release is planned. Workflows, terminology, and outputs of INTERPRET NTA provide a focal point for necessary discussions on the harmonization of NTA QA/QC practices.

In 2011, 68 archived beluga whale (Delphinapterus leucas) liver samples collected from Cook Inlet and the eastern Chukchi Sea from 1989 to 2006 were characterized for 12 per- and polyfluoroalkyl substances (PFAS) using targeted mass spectroscopy (MS) methods; however, at the time of the original analysis, high resolution MS (HRMS) methods were not readily available. This follow-up study utilizes both targeted as well as cutting-edge HRMS non-targeted analysis (NTA) techniques to screen for additional PFAS as well as potential contaminants of emerging concern (CECs) in the chemical space under investigation. Targeted analysis detected perfluorodecanesulfonic acid (PFDS) and perfluoroheptane sulfonic acid (PFHpS) in 10 % and 9 % of liver samples, respectively. PFDS detections were observed only in Cook Inlet whales while PFHpS was detected in whales from both locations. In addition, NTA identified four dibrominated pyrrole ring structures two with a sulfate (C8H11NBr2SO3, and C9H13NBr2SO3, Schymanski level 3), and two with either a sulfonate or a sulfate and hydroxy group (C8H11NBr2SO4, C9H13NBr2SO4, Schymanski level 4) in whales from the eastern Chukchi Sea. Literature search reveals similar brominated metabolites from marine bacteria, sponges, and other marine organisms, suggesting the brominated CECs are of marine origin.

With increasing public awareness of PFAS, and their presence in biological and environmental media across the globe, comes a matching increase in the number of PFAS monitoring studies. As more matrices and sample cohorts are examined, there are more opportunities for matrix interferents to appear as PFAS where there are none (i.e., "seeing ghosts"), impacting subsequent reports. Addressing these ghosts is vital for the research community, as proper analytical measurements are necessary for decision-makers to understand the presence, levels, and potential risks associated with PFAS and protect human and environmental health. To date, PFAS interference has been identified in several matrices (e.g., food, shellfish, blood, tissue); however, additional unidentified interferents are likely to be observed as PFAS research continues to expand. Therefore, the aim of this commentary is several fold: (1) to create and support a publicly available dataset of all currently known PFAS analytical interferents, (2) to allow for the expansion of that dataset as more sources of interference are identified, and (3) to advise the wider scientific community on how to both identify and eliminate current or new analytical interference in PFAS analyses.

A fluorochemical facility near Fayetteville, North Carolina, emitted per- and polyfluoroalkyl ether acids (PFEAs), a subgroup of per- and polyfluoroalkyl substances (PFAS), to air. Analyze PFAS in private wells near the facility and in blood from well users to assess relationships between PFEA levels in water and serum. In 2019, we recruited private well users into the GenX Exposure Study and collected well water and blood samples. We targeted 26 PFAS (11 PFEAs) in water and 27 PFAS (9 PFEAs) in serum using liquid chromatography-mass spectrometry. We used regression modeling to explore relationships between water and serum PFAS. For the only PFEA detected frequently in water and serum, Nafion byproduct 2, we used generalized estimating equation (GEE) models to assess well water exposure metrics and then adjusted for covariates that may influence Nafion byproduct 2 serum concentrations. We enrolled 153 participants ages 6 and older (median = 56 years) using 84 private wells. Most wells (74%) had ≥6 detectable PFEAs; median ∑PFEAs was 842 ng/L (interquartile range = 197–1760 ng/L). Low molecular weight PFEAs (PMPA, HFPO-DA [GenX], PEPA, PFO2HxA) were frequently detected in well water, had the highest median concentrations, but were not detectable in serum. Nafion byproduct 2 was detected in 73% of wells (median = 14 ng/L) and 56% of serum samples (median = 0.2 ng/mL). Cumulative dose (well concentration × duration at address) was positively associated with Nafion byproduct 2 serum levels and explained the most variability (10%). In the adjusted model, cumulative dose was associated with higher Nafion byproduct 2 serum levels while time outside the home was associated with lower levels. PFAS are a large class of synthetic, fluorinated chemicals. Fluorochemical facilities are important sources of environmental PFAS contamination globally. The fluorochemical industry is producing derivatives of perfluoroalkyl acids, including per- and polyfluoroalkyl ether acids (PFEAs). PFEAs have been detected in various environmental samples but information on PFEA-exposed populations is limited. While serum biomonitoring is often used for PFAS exposure assessment, serum biomarkers were not good measures of long-term exposure to low molecular weight PFEAs in a private well community. Environmental measurements and other approaches besides serum monitoring will be needed to better characterize PFEA exposure.

The recent application of non-targeted analysis (NTA) techniques in environmental monitoring has revealed numerous novel fluorinated species in surface water, wildlife, and humans in the Cape Fear River (CFR) region of North Carolina. In this study, we have re-examined archived alligator, striped bass, horse, and dog serum as well as archived seabird tissue data from previously reported exposure studies in order to extend the panel of detected novel PFAS. In this study, the compounds CF3-(OCF2)x-COOH, x = 6, 7, 8 (Abbreviated PFO6TeDA, PFO7HxDA, PFO8OcDA, respectively), and 6H-Perfluoro-3-oxa,4-methylhexanesulfonic acid (Nafion byproduct 6) were detected for the first time in environmental tissues even though these analytes were not previously detected in the CFR. Analytical standards were available for PFO6TeDA and Nafion Byproduct 6, and therefore, were quantitated in investigated tissues. PFO7HxDA and PFO8OcDA had no available standards and were semi-quantitated using NTA techniques. Of note, PFO6TeDA, PFO7HxDA, and PFO8OcDA were observed in alligator, bass, and seabird but not horse and dog. PFO6TeDA was detected at the highest frequency in all investigated tissues with PFO7HxDA and PFO8OcDA detected at lower frequencies. No Nafion Byproduct 6 values are reported in serum due to poor analytical reproducibility of the measurements. Seabird tissue to blood ratios suggests PFO6TeDA is highest in the heart, kidney, and liver and lowest in the brain. Overall, additional studies are needed to fully understand the potential impact of these additional novel PFAS on both wildlife and humans in the CFR region.

Non-targeted analysis (NTA) is an increasingly popular technique for characterizing undefined chemical analytes. Generating quantitative NTA (qNTA) concentration estimates requires the use of training data from calibration “surrogates,” which can yield diminished predictive performance relative to targeted analysis. To evaluate performance differences between targeted and qNTA approaches, we defined new metrics that convey predictive accuracy, uncertainty (using 95% inverse confidence intervals), and reliability (the extent to which confidence intervals contain true values). We calculated and examined these newly defined metrics across five quantitative approaches applied to a mixture of 29 per- and polyfluoroalkyl substances (PFAS). The quantitative approaches spanned a traditional targeted design using chemical-specific calibration curves to a generalizable qNTA design using bootstrap-sampled calibration values from “global” chemical surrogates. As expected, the targeted approaches performed best, with major benefits realized from matched calibration curves and internal standard correction. In comparison to the benchmark targeted approach, the most generalizable qNTA approach (using “global” surrogates) showed a decrease in accuracy by a factor of ~4, an increase in uncertainty by a factor of ~1000, and a decrease in reliability by ~5%, on average. Using “expert-selected” surrogates ( n = 3) instead of “global” surrogates ( n = 25) for qNTA yielded improvements in predictive accuracy (by ~1.5×) and uncertainty (by ~70×) but at the cost of further-reduced reliability (by ~5%). Overall, our results illustrate the utility of qNTA approaches for a subclass of emerging contaminants and present a framework on which to develop new approaches for more complex use cases. Graphical Abstract

Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

Most people in the United States have been exposed to per- and polyfluoroalkyl substances (PFAS) which have been linked to a wide array of adverse health conditions in adults and children. The consumption of contaminated drinking water is an important human exposure pathway to PFAS. Residential sources also contribute to PFAS exposure through dermal contact and ingestion of house dust, which acts as an aggregate of chemicals from sources like furnishing materials and consumer products. The U.S. Department of Housing and Urban Development (HUD) conducted the first nationwide survey of residential hazards called the American Healthy Homes Survey (AHHS) in 2005, followed by a second survey (AHHS II) in 2017. The U.S. Environmental Protection Agency (EPA) collaborated with HUD on both efforts and subsequently analyzed PFAS in household tap water and house dust collected from the same homes during the AHHS II study. This study leverages these paired samples to investigate potentially important exposure sources and pathways in the residential environment. Here we report results for paired household tap water and house dust samples from 241 homes for 13 and 16 PFAS chemicals, respectively. All 13 targeted chemicals were detected in the household tap water samples with detections ranging from 100 % for PFBS to 1 % for PFNS, and all 16 targeted chemicals were detected in the house dust samples with detections ranging from 97 % for PFOA to 9 % for PFNS. Four chemicals (PFOA, PFOS, PFHxS, and PFHpA) were measured above the limit of detection in at least 50 % of the samples in both media. All households had at least one of the targeted PFAS detected in both their tap water and house dust. Results provided evidence that geographical factors, such as proximity to ambient contamination sources, were main drivers of PFAS contamination in tap water, while PFAS contamination in house dust was driven mainly by within-home sources. Exposure estimates calculated from the measured PFAS concentrations highlight the importance of addressing potential sources of exposure to PFAS within homes in addition to ambient sources affecting communities' drinking water, particularly to reduce children's exposure to these chemicals.

Per- and poly-fluoroalkyl substances (PFAS) are chemicals of concern-they are ubiquitous, persistent, with known and suspected health impacts. Well studied, primary sources of exposure to PFAS are drinking water and food. The presence of PFAS in human tissue of general populations suggests other important exposure sources/pathways. House dust measurements suggest widespread presence of PFAS in residences. Limited studies report paired analyses of PFAS occurrence in indoor media and PFAS concentrations in serum. While paired samples of house dust and blood serum are currently rare, the National Children's Study (NCS) contains paired samples, as well as sociodemographic information, from pregnant people that participated in the study. These archived NCS data and specimens for 104 participants collected between 2009 and 2014 were leveraged and analyzed for 16 commonly measured PFAS. We evaluated PFAS levels in the home, and the relationships between PFAS in dust and serum, and sociodemographic or housing variables. In addition, mechanistic exposure models, and then steady-state serum level models with simple parameters were used to estimate dust contributions of PFAS to serum. The geometric means for the most commonly found PFAS (full names in table 1) in serum were: 4.1 ng/mL for PFOS, 1.1 ng/mL for PFOA, 0.87 ng/mL for PFHxS, 0.16 ng/mL for PFDA. The geometric means of PFAS in dust were: 17 mu g/kg for PFOS, 16 mu g/kg for PFOA, 9.6 mu g/kg for PFDS, 4.5 mu g/kg for PFHpA, 4.4 mu g/kg for PFNA, 3.9 mu g/kg for PFHxS, 3.5 mu g/kg for PFDA, 2.3 mu g/kg for PFDoA, 2.1 mu g/kg for PFUdA. PFOA was significantly correlated in serum and dust as was the sum of all PFAS detected in > 50 % of serum and dust. PFAS in serum was significantly associated with: Higher income, recent renovations, years lived in the home, and educational attainment. PFAS in dust was significantly associated with: Higher participant age, type of home, amount of carpet, educational attainment, higher income, recent renovation, and membership in the military. For some PFAS, 25 % of the overall exposure, on average, is from dust, but for others, 3-4 % is attributed to dust. We were able to identify important associations in PFAS exposure in the homes of pregnant people based on paired serum and dust samples. This built a clearer picture of which PFAS and at what quantities they exist in these homes, how they relate to each other, and how they are tied to sociodemographic and housing factors. Our results demonstrate that exposure to PFAS via house dust may contribute up to 25% of total exposure for adults, highlighting the importance of understanding what drives residential exposures.

BACKGROUND:The intersection of the topics of high-resolution mass spectrometry (HRMS) and per- and polyfluoroalkyl substances (PFAS) bring together two disparate and complex subjects. Recently non-targeted analysis (NTA) for the discovery of novel PFAS in environmental and biological media has been shown to be valuable in multiple applications. Classical targeted analysis for PFAS using LC-MS/MS, though growing in compound coverage, is still unable to inform a holistic understanding of the PFAS burden in most samples. NTA fills at least a portion of this data gap. OBJECTIVES:Entrance into the study of novel PFAS discovery requires identification techniques such as HRMS (e.g., QTOF and Orbitrap) instrumentation. This requires practical knowledge of best approaches depending on the purpose of the analyses. The utility of HRMS applications for PFAS discovery is unquestioned and will likely play a significant role in many future environmental and human exposure studies. METHODS/RESULTS:PFAS have some characteristics that make them standout from most other chemicals present in samples. Through a series of tell-tale PFAS characteristics (e.g., characteristic mass defect range, homologous series and characteristic fragmentation patterns), and case studies different approaches and remaining challenges are demonstrated. IMPACT STATEMENT:The identification of novel PFAS via non-targeted analysis using high resolution mass spectrometry is an important and difficult endeavor. This synopsis document will hopefully make current and future efforts on this topic easier to perform for novice and experienced alike. The typical time devoted to NTA PFAS investigations (weeks to months or more) may benefit from these practical steps employed.

To estimate half-lives for novel fluoroethers, the GenX Exposure Study obtained two serum measurements for per- and polyfluoroalkyl substances (PFAS) for 44 participants of age 12-86 years from North Carolina, collected 5 and 11 months after fluoroether discharges into the drinking water source were controlled. The estimated half-lives for these compounds were 127 days (95% confidence interval (95% CI) = 86, 243 days) for perfluorotetraoxadecanoic acid (PFO4DA), 296 days for Nafion byproduct 2 (95% CI = 176, 924 days), and 379 days (95% CI = 199, 3870 days) for perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA). Using these estimates and the literature values, a model was built that predicted PFAS half-lives using structural properties. Three chemical properties predicted 55% of the variance of PFAS half-lives based on 15 PFAS. A model with only molecular weight predicted 69% of the variance. Some properties can predict the half-lives of PFAS, but a deeper understanding is needed. These fluoroethers had biological half-lives longer than published half-lives for PFHxA and PFHpA (30-60 days) but shorter than those for PFOA and PFOS (800-1200 days). These are the first and possibly only estimates of human elimination half-lives of these fluoroethers.