Retrospective chart review of GI bleeding in people with von Willebrand disease.

INTRODUCTION: Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options. AIM: Describe current treatments and outcomes for GI BEs in people with VWD. METHODS: This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5 years. Baseline characteristics, number and aetiology of BEs, associated GI-specific morbidities/lesions, treatment and outcomes were analysed descriptively. RESULTS: Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5-year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non-haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non-VWF treatments tended to resolve later. In patients with GI-specific morbidities/lesions, 84% resolved with first-line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on-demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution. CONCLUSIONS: This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis.

Early diagnosis of persons with von Willebrand disease using a machine learning algorithm and real-world data.

BACKGROUND: Von Willebrand disease (VWD) is underdiagnosed, often delaying treatment. VWD claims coding is limited and includes no severity qualifiers; improved identification methods for VWD are needed. The aim of this study is to identify and characterize undiagnosed symptomatic persons with VWD in the US from medical insurance claims using predictive machine learning (ML) models. RESEARCH DESIGN AND METHODS: Diagnosed and potentially undiagnosed VWD cohorts were defined using Komodo longitudinal US claims data (January 2015-March 2020). ML models were built using key characteristics predictive of VWD diagnosis from the diagnosed cohort. Two ML models predicted VWD diagnosis with the highest accuracy in females (random forest; 84%) and males (gradient boosting machine; 85%). Undiagnosed persons suspected to have VWD were identified using an 80% cutoff probability; profiles of key characteristics were constructed. RESULTS: The trained ML models were applied to the undiagnosed cohort (28,463 females; 20,439 males) with suspected VWD. Fifty-two percent of undiagnosed females had heavy menstrual bleeding, a key pre-diagnosis symptom. Undiagnosed males tended to have more frequent medical procedures, hospitalizations, and emergency room visits compared with undiagnosed females. CONCLUSIONS: ML algorithms successfully identified potentially undiagnosed symptomatic people with VWD, although many may remain undiagnosed and undertreated. External validation of the algorithms is recommended.

Grouping strategies for assessing and managing persistent and mobile substances.

Background: Persistent, mobile and toxic (PMT), or very persistent and very mobile (vPvM) substances are a wide class of chemicals that are recalcitrant to degradation, easily transported, and potentially harmful to humans and the environment. Due to their persistence and mobility, these substances are often widespread in the environment once emitted, particularly in water resources, causing increased challenges during water treatment processes. Some PMT/vPvM substances such as GenX and perfluorobutane sulfonic acid have been identified as substances of very high concern (SVHCs) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. With hundreds to thousands of potential PMT/vPvM substances yet to be assessed and managed, effective and efficient approaches that avoid a case-by-case assessment and prevent regrettable substitution are necessary to achieve the European Union's zero-pollution goal for a non-toxic environment by 2050. Main: Substance grouping has helped global regulation of some highly hazardous chemicals, e.g., through the Montreal Protocol and the Stockholm Convention. This article explores the potential of grouping strategies for identifying, assessing and managing PMT/vPvM substances. The aim is to facilitate early identification of lesser-known or new substances that potentially meet PMT/vPvM criteria, prompt additional testing, avoid regrettable use or substitution, and integrate into existing risk management strategies. Thus, this article provides an overview of PMT/vPvM substances and reviews the definition of PMT/vPvM criteria and various lists of PMT/vPvM substances available. It covers the current definition of groups, compares the use of substance grouping for hazard assessment and regulation, and discusses the advantages and disadvantages of grouping substances for regulation. The article then explores strategies for grouping PMT/vPvM substances, including read-across, structural similarity and commonly retained moieties, as well as the potential application of these strategies using cheminformatics to predict P, M and T properties for selected examples. Conclusions: Effective substance grouping can accelerate the assessment and management of PMT/vPvM substances, especially for substances that lack information. Advances to read-across methods and cheminformatics tools are needed to support efficient and effective chemical management, preventing broad entry of hazardous chemicals into the global market and favouring safer and more sustainable alternatives.

Should Transformation Products Change the Way We Manage Chemicals?

When chemical pollutants enter the environment, they can undergo diverse transformation processes, forming a wide range of transformation products (TPs), some of them benign and others more harmful than their precursors. To date, the majority of TPs remain largely unrecognized and unregulated, particularly as TPs are generally not part of routine chemical risk or hazard assessment. Since many TPs formed from oxidative processes are more polar than their precursors, they may be especially relevant in the context of persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances, which are two new hazard classes that have recently been established on a European level. We highlight herein that as a result, TPs deserve more attention in research, chemicals regulation, and chemicals management. This perspective summarizes the main challenges preventing a better integration of TPs in these areas: (1) the lack of reliable high-throughput TP identification methods, (2) uncertainties in TP prediction, (3) inadequately considered TP formation during (advanced) water treatment, and (4) insufficient integration and harmonization of TPs in most regulatory frameworks. A way forward to tackle these challenges and integrate TPs into chemical management is proposed.

Novel echocardiographic pixel intensity quantification method for differentiating transthyretin cardiac amyloidosis from light chain cardiac amyloidosis and other phenocopies.

AIMS: Differentiating cardiac amyloidosis (CA) subtypes is important considering the significantly different therapies for transthyretin (ATTR)-CA and light chain (AL)-CA. Therefore, an echocardiographic method to distinguish ATTR-CA from AL-CA would provide significant value. We assessed a novel echocardiographic pixel intensity method to quantify myocardial calcification to differentiate ATTR-CA from phenocopies of CA and from AL-CA, specifically. METHODS AND RESULTS: 167 patients with ATTR-CA (n=53), AL-CA (n=32), hypertrophic cardiomyopathy (n=37), and advanced chronic kidney disease (n=45) were retrospectively evaluated. The septal reflectivity ratio (SRR) was measured as the average pixel intensity of the visible anterior septal wall divided by the average pixel intensity of the visible posterior lateral wall. SRR and other myocardial strain-based echocardiographic measures were evaluated with receiver operator characteristic analysis to evaluate accuracy in distinguishing ATTR-CA from AL-CA and other forms of left ventricular hypertrophy. Mean septal reflectivity ratio (SRR) was significantly higher in the ATTR-CA cohort compared to the other cohorts (p <0.001). SRR demonstrated the largest AUC (0.91, p<0.0001) for distinguishing ATTR from all other cohorts and specifically for distinguishing ATTR-CA from AL-CA (AUC=0.90, p<0.0001, specificity 96%, sensitivity 63%). There was excellent inter- and intra-operator reproducibility with an ICC of 0.91 (p <0.001) and 0.89 (p <0.001), respectively. CONCLUSION: The SRR is a reproducible and robust parameter for differentiating ATTR-CA from other phenocopies of CA and specifically ATTR-CA from AL-CA.

Distal Versus Proximal Radial Artery Access for Cardiac Catheterization: 1-Year Outcomes.

Proximal radial artery (PRA) access for cardiac catheterization is safe but can jeopardize subsequent use of the artery because of occlusion. Distal radial artery (DRA) access in the anatomical snuffbox preserves the RA but safety and potential detrimental effects on hand function are unknown. We aimed to assess hand function and complications after DRA and PRA. In this single-center trial, 300 patients were randomly allocated 1:1 to cardiac catheterization through DRA or PRA. The primary end point of change in hand function from baseline to 1 year was a composite of the Quick Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, hand grip test, and thumb-forefinger pinch test. The secondary end points included access feasibility and complications. Of 216 patients with 1-year completed follow-up, 112 were randomly allocated to DRA and 104 to PRA, with balanced demographics and procedural characteristics. Both groups had similar access site bleeding rates (DRA 0% vs PRA 1.4%, p = 0.25). Radial artery occlusion occurred in 1 PRA patient versus 2 in DRA. There was no significant difference in change of hand function, median (interquartile range) hand grip (DRA 0.7 [-3 to 4.5] vs PRA 1.3 [-2 to 4.3] kg, p = 0.57), pinch grip (DRA -0.1 [-1.1 to 1] vs PRA -0.3 [-1 to 0.7] kg, p = 0.66), and Quick DASH (DRA 0 [-6.6 to 2.3] vs PRA 0 [-4.6 to 2.9] points, p = 0.58). The composite of hand function was comparable between PRA and DRA. In conclusion, DRA is a safe strategy for cardiac catheterization, with a low complication rate. Compared with PRA, there is no increased risk of hand dysfunction or radial artery occlusion at 1 year.

Effect-Directed Analysis Based on Transthyretin Binding Activity of Per- and Polyfluoroalkyl Substances in a Contaminated Sediment Extract.

Only a fraction of the total number of per- and polyfluoroalkyl substances (PFAS) are monitored on a routine basis using targeted chemical analyses. We report on an approach toward identifying bioactive substances in environmental samples using effect-directed analysis by combining toxicity testing, targeted chemical analyses, and suspect screening. PFAS compete with the thyroid hormone thyroxin (T4 ) for binding to its distributor protein transthyretin (TTR). Therefore, a TTR-binding bioassay was used to prioritize unknown features for chemical identification in a PFAS-contaminated sediment sample collected downstream of a factory producing PFAS-coated paper. First, the TTR-binding potencies of 31 analytical PFAS standards were determined. Potencies varied between PFAS depending on carbon chain length, functional group, and, for precursors to perfluoroalkyl sulfonic acids (PFSA), the size or number of atoms in the group(s) attached to the nitrogen. The most potent PFAS were the seven- and eight-carbon PFSA, perfluoroheptane sulfonic acid (PFHpS) and perfluorooctane sulfonic acid (PFOS), and the eight-carbon perfluoroalkyl carboxylic acid (PFCA), perfluorooctanoic acid (PFOA), which showed approximately four- and five-times weaker potencies, respectively, compared with the native ligand T4 . For some of the other PFAS tested, TTR-binding potencies were weak or not observed at all. For the environmental sediment sample, not all of the bioactivity observed in the TTR-binding assay could be assigned to the PFAS quantified using targeted chemical analyses. Therefore, suspect screening was applied to the retention times corresponding to observed TTR binding, and five candidates were identified. Targeted analyses showed that the sediment was dominated by the di-substituted phosphate ester of N-ethyl perfluorooctane sulfonamido ethanol (SAmPAP diester), whereas it was not bioactive in the assay. SAmPAP diester has the potential for (bio)transformation into smaller PFAS, including PFOS. Therefore, when it comes to TTR binding, the hazard associated with this substance is likely through (bio)transformation into more potent transformation products. Environ Toxicol Chem 2024;43:245-258. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Per- and polyfluoroalkyl substance (PFAS) removal from soil washing water by coagulation and flocculation.

Soil washing is currently attracting attention as a promising remediation strategy for land contaminated with per- and polyfluoroalkyl substances (PFAS). In the soil washing process, the contaminant is transferred from the soil into the liquid phase, producing a PFAS contaminated process water. One way to treat such process water is to use coagulation and flocculation; however, few studies are available on the performance of coagulation and flocculation for removing PFAS from such process water. This study evaluated 6 coagulants and flocculants (polyaluminium chloride (PACl), zirconium oxychloride octahydrate, cationic and anionic polyacrylamide, Polyclay 685 and Perfluor Ad®), for the treatment of a proxy PFAS contaminated washing water, spiked with PFAS concentrations found at typical Aqueous Film Forming Foam (AFFF) contaminated sites. PFAS removal efficiencies (at constant pH) varied greatly depending on the coagulants and flocculants, as well as the dosage used and the targeted PFAS. All tested coagulants and flocculants reduced the turbidity by >95%, depending on the dosage. Perfluor Ad®, a specially designed coagulant, showed the highest removal efficiency for all longer chain (>99%) and shorter chain PFAS (>68%). The cationic polyacrylamide polymer removed longer chain PFAS up to an average of 80%, whereas average shorter chain PFAS removal was lower (<30%). The two metal-based coagulants tested, PACl and zirconium, removed longer chain PFAS by up to an average of 61% and shorter chain PFAS up to 48%. Polyclay 685, a mixture of powdered activated carbon (PAC) and aluminium sulphate, removed longer chain PFAS by 90% and shorter chain PFAS on average by 76%, when very high dosages of the coagulant were used (2,000 mg/L). PFAS removal efficiencies correlated with chain length and headgroup. Shorter chain PFAS removal was dependent on electrostatic interaction with the precipitating flocs, whereas for longer chain PFAS, hydrophobic interactions between apolar functional groups and flocs created by the coagulant/flocculant, dissolved organic matter and suspended solids played a major role. The results of this study showed that by selecting the most efficient coagulant and aqueous conditions, a greater amount of PFAS can be removed from process waters in soil washing facilities, and thus included as part of various treatment trains.

Distal Versus Proximal Radial Artery Access for Cardiac Catheterization: 30-Day Outcomes of the DIPRA Study.

Background Proximal radial artery (pRA) access for cardiac catheterization is safe but can jeopardize subsequent use of the artery because of occlusion. Distal radial artery (dRA) access in the anatomical snuffbox preserves the radial artery, but safety and potential detrimental effects on hand function are unknown. Methods and Results In the DIPRA (Distal Versus Proximal Radial Artery Access for Cardiac Catheterization and Intervention) study, a single-center trial, 300 patients were randomized 1:1 to cardiac catheterization through dRA or pRA. The primary end point of change in hand function from baseline to 30 days was a composite of the QuickDASH (Quick Disabilities of the Arm, Shoulder and Hand) questionnaire, hand-grip test, and thumb forefinger pinch test. Secondary end points included access feasibility and complications; 254 of 300 patients completed follow-up at 30 days; of these, 128 were randomized to dRA and 126 to pRA with balanced demographic and procedural characteristics. Both groups had similar rates of access site bleeding (dRA 0% versus pRA 1.4%; P=0.25). Six patients with dRA failed access compared with 2 patients with pRA. Radial artery occlusion occurred in 2 pRA versus none in dRA. There were no significant differences in change in hand function, median hand-grip (dRA 0 [-3.2, 3.3] versus pRA 0.7 [-2.3, 3.3] kg; P=0.21), pinch-grip (dRA -0.3 [-1.2, 0.5] versus pRA 0 [-0.9, 0.9] kg; P=0.09), and QuickDASH (dRA 0 [-4.6, 2.3] versus pRA 0 [-4.6, 2.3] points, P=0.96). There was no significant difference in the composite of hand function between pRA and dRA. Conclusions dRA is a safe strategy for cardiac catheterization with a low complication rate. Compared with pRA, there is no increased risk of hand dysfunction at 30 days. Registration URL: https://www.ClinicalTrials.gov. Unique identifier: NCT04318990.

Influence of grain size, organic carbon and organic matter residue content on the sorption of per- and polyfluoroalkyl substances in aqueous film forming foam contaminated soils - Implications for remediation using soil washing.

A soil that was historically contaminated with Aqueous Film Forming Foam (AFFF) was dry sieved into size fractions representative of those produced during soil washing. Batch sorption tests were then conducted to investigate the effect of soil parameters on in situ per- and polyfluoroalkyl substances (PFAS) sorption of these different size fractions: < 0.063 mm, 0.063 to 0.5 mm, 0.5 to 2 mm, 2 to 4 mm, 4 to 8 mm, and soil organic matter residues (SOMR). PFOS (513 ng/g), 6:2 FTS (132 ng/g) and PFHxS (58 ng/g) were the most dominant PFAS in the AFFF contaminated soil. Non-spiked, in situ Kd values for 19 PFAS ranged from 0.2 to 138 L/Kg (log Kd -0.8 to 2.14) for the bulk soil and were dependant on the head group and perfluorinated chain length (spanning C4 to C13). The Kd values increased with decreasing grain size and increasing organic carbon content (OC), which were correlated to each other. For example, the PFOS Kd value for silt and clay (< 0.063 mm, 17.1 L/Kg, log Kd 1.23) were approximately 30 times higher compared to the gravel fraction (4 to 8 mm, 0.6 L/Kg, log Kd -0.25). The highest PFOS Kd value (116.6 L/Kg, log Kd 2.07) was found for the SOMR fraction, which had the highest OC content. Koc values for PFOS ranged from 6.9 L/Kg (log Koc 0.84) for the gravel fraction to 1906 L/Kg (log Koc 3.28) for the silt and clay, indicating that the mineral composition of the different size fractions also influenced sorption. The results here emphasize the need to separate coarse-grained fractions and fine-grained fractions, and in particular the SOMR, to optimize the soil washing process. Higher Kd values for the smaller size fractions indicate that coarser soils are better suited for soil washing.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for mucocutaneous bleeding disorders.

BACKGROUND: Excessive or abnormal mucocutaneous bleeding (MCB) may impact all aspects of the physical and psychosocial wellbeing of those who live with it (PWMCB). The evidence base for the optimal diagnosis and management of disorders such as inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD), Ehlers-Danlos syndromes (EDS), and von Willebrand disease (VWD) remains thin with enormous potential for targeted research. RESEARCH DESIGN AND METHODS: National Hemophilia Foundation and American Thrombosis and Hemostasis Network initiated the development of a National Research Blueprint for Inherited Bleeding Disorders with extensive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them. They recruited multidisciplinary expert working groups (WG) to distill community-identified priorities into concrete research questions and score their feasibility, impact, and risk. RESULTS: WG2 detailed 38 high priority research questions concerning the biology of MCB, VWD, inherited qualitative platelet function defects, HDS/EDS, HHT, bleeding disorder of unknown cause, novel therapeutics, and aging. CONCLUSIONS: Improving our understanding of the basic biology of MCB, large cohort longitudinal natural history studies, collaboration, and creative approaches to novel therapeutics will be important in maximizing the benefit of future research for the entire MCB community.

More people experience mucocutaneous bleeding (MCB), affecting tissues like skin and gums, than have hemophilia A or B. MCB is not understood as well as hemophilia. Common types of MCB include nosebleeds, bleeding gums, heavy menstrual bleeding, and digestive tract bleeding. Mucocutaneous inherited bleeding disorders include inherited platelet disorders, hereditary hemorrhagic telangiectasia (HHT), hypermobility spectrum disorders (HSD) and Ehlers-Danlos syndromes (EDS), von Willebrand Disease (VWD), and others. Diagnosing and treating MCB is complicated and sometimes medical providers dismiss the bleeding that patients report when they cannot find a medical explanation for it. Many people with mucocutaneous bleeding (PWMCB) do not receive the care they need; for example, women with VWD live with symptoms for, on average, 16 years before they are diagnosed in the US. This struggle to obtain care has important negative impacts on patients' physical and psychological health and their quality-of-life. The National Hemophilia Foundation (NHF), a large US bleeding disorders patient advocacy organization, set out to develop a National Research Blueprint for Inherited Bleeding Disorders focused on community priorities. They brought together a group of patients, providers, and researchers with MCB expertise to identify the research that would most improve the lives of PWMCB through targeted and accessible diagnostics and therapies. We report in this paper that research is needed to better understand the biology of MCB and to define the mechanisms of disease in these disorders. We also describe high priority research questions for each of the main disorders, novel therapeutics, and aging.

Targeting Ultrasmall Gold Nanoparticles with cRGD Peptide Increases the Uptake and Efficacy of Cytotoxic Payload.

Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVß3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVß3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs.

Assessing the Persistence and Mobility of Organic Substances to Protect Freshwater Resources.

Persistent and mobile organic substances are those with the highest propensity to be widely distributed in groundwater and thereby, when emitted at low-levels, to contaminate drinking water extraction points and freshwater environments. To prevent such contamination, the European Commission is in the process of introducing new hazard classes for persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances within its key chemical regulations CLP and REACH. The assessment of persistence in these regulations will likely be based on simulated half-life, t 1/2, thresholds; the assessment of mobility will likely be based on organic carbon-water distribution coefficient, K OC, thresholds. This study reviews the use of t 1/2 and K OC to describe persistence and mobility, considering the theory, history, suitability, data limitations, estimation methods, and alternative parameters. For this purpose, t 1/2, K OC, and alternative parameters were compiled for substances registered under REACH, known transformation products, and substances detected in wastewater treatment plant effluent, surface water, bank filtrate, groundwater, raw water, and drinking water. Experimental t 1/2 values were rare and only available for 2.2% of the 14 203 unique chemicals identified. K OC data were only available for a fifth of the substances. Therefore, the usage of alternative screening parameters was investigated to predict t 1/2 and K OC values, to assist weight-of-evidence based PMT/vPvM hazard assessments. Even when considering screening parameters, for 41% of substances, PMT/vPvM assessments could not be made due to data gaps; for 23% of substances, PMT/vPvM assessments were ambiguous. Further effort is needed to close these substantial data gaps. However, when data is available, the use of t 1/2 and K OC is considered fit-for-purpose for defining PMT/vPvM thresholds. Using currently discussed threshold values, between 1.9 and 2.6% of REACH registered substances were identified as PMT/vPvM. Among the REACH registered substances detected in drinking water sources, 24-30% were PMT/vPvM substances.

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry.

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/). Supplementary Information: The online version contains supplementary material available at 10.1186/s12302-022-00680-6.

Occurrence, Distribution, and Environmental Behavior of Persistent, Mobile, and Toxic (PMT) and Very Persistent and Very Mobile (vPvM) Substances in the Sources of German Drinking Water.

Persistent, mobile, and toxic (PMT) and very persistent and very mobile (vPvM) substances have been recognized as a threat to both the aquatic environment and to drinking water resources. These substances are currently prioritized for regulatory action by the European Commission, whereby a proposal for the inclusion of hazard classes for PMT and vPvM substances has been put forward. Comprehensive monitoring data for many PMT/vPvM substances in drinking water sources are scarce. Herein, we analyze 34 PMT/vPvM substances in 46 surface water, groundwater, bank filtrate, and raw water samples taken throughout Germany. Results of the sampling campaign demonstrated that known PMT/vPvM substances such as 1H-benzotriazole, melamine, cyanuric acid, and 1,4-dioxane are responsible for substantial contamination in the sources of German drinking water. In addition, the results revealed the widespread presence of the emerging substances 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and diphenylguanidine (DPG). A correlation analysis showed a pronounced co-occurrence of PMT/vPvM substances associated predominantly with consumer or professional uses and also demonstrated an inhomogeneous co-occurrence for substances associated mainly with industrial use. These data were used to test the hypothesis that most PMT/vPvM substances pass bank filtration without significant concentration reduction, which is one of the main reasons for introducing PMT/vPvM as a hazard class within Europe.

Ultra-Short-Chain PFASs in the Sources of German Drinking Water: Prevalent, Overlooked, Difficult to Remove, and Unregulated.

Per- and polyfluoroalkyl substances (PFASs) have been a focal point of environmental chemistry and chemical regulation in recent years, culminating in a shift from individual PFAS regulation toward a PFAS group regulatory approach in Europe. PFASs are a highly diverse group of substances, and knowledge about this group is still scarce beyond the well-studied, legacy long-chain, and short-chain perfluorocarboxylates (PFCAs) and perfluorosulfonates (PFSAs). Herein, quantitative and semiquantitative data for 43 legacy short-chain and ultra-short-chain PFASs (≤2 perfluorocarbon atoms for PFCAs, ≤3 for PFSAs and other PFASs) in 46 water samples collected from 13 different sources of German drinking water are presented. The PFASs considered include novel compounds like hexafluoroisopropanol, bis(trifluoromethylsulfonyl)imide, and tris(pentafluoroethyl)trifluorophosphate. The ultra-short-chain PFASs trifluoroacetate, perfluoropropanoate, and trifluoromethanesulfonate were ubiquitous and present at the highest concentrations (98% of sum target PFAS concentrations). "PFAS total" parameters like the adsorbable organic fluorine (AOF) and total oxidizable precursor (TOP) assay were found to provide only an incomplete picture of PFAS contamination in these water samples by not capturing these highly prevalent ultra-short-chain PFASs. These ultra-short-chain PFASs represent a major challenge for drinking water production and show that regulation in the form of preventive measures is required to manage them.