Cyanotoxins: methods and approaches for their analysis and detection

Cyanotoxins are secondary metabolites produced by cyanobacteria, a group of photosynthetic prokaryota especially found in freshwater. In favourable conditions (i.e. high nutrient levels, light intensity, water temperature), cyanobacteria can form blooms, a natural phenomenon characterised by an algal biomass accumulation and the possible release of cyanotoxins in water ecosystems. Toxins represent an emerging threats for the aquatic organisms which can bioaccumulate these compounds and transfer them throughout the food chain to wildlife and humans. Other ways of exposure for humans include the oral, dermal and inhalation route. The consumption of contaminated drinking water, skin contact and swallowing water during recreational activities are among the most frequently reasons for human poisonings caused by cyanotoxins. The associated symptoms usually range from severe headache to fever, respiratory paralysis and in rare case, death. The World Health Organization (WHO) has issued a provisional guideline value of 1 µg/L in drinking water for Microcystin-LR (MC-LR), the most toxic, widespread and common toxin in water supplies. Due to the lack of complete toxicological data for a range of cyanotoxins, their concentration in drinking water is not yet well regulated even in countries belonging to the European Union (EU). In this report, attention is focused on the methodologies commonly used to detect cyanotoxins in water environments. These applications can be grouped in: I) microscopy analysis II) physicochemical methods III) molecular-based methods IV) biochemical-based methods V) chemical methods. Each technique shows specific limitations in terms of sensitivity, reliability and limit of detection. The choice of the best one to use is determined in accordance with the information they provide, the availability of facilities and the technical expertise of the operators. Most of the research about cyanotoxins has been mainly focused on microcystins (MCs). The other cyanotoxins have been much less investigated and more tools need to be developed to overcome this problem. Notwithstanding there is no a single analytical application able to detect all cyanotoxin variants in an environmental sample. Some current methods described in this report show great promise in terms of being simple, cost-effective, specific and sensitive for the analysis of a defined toxin.JRC.D.2-Water and Marine Resource

Review of the 1st Watch List under the Water Framework Directive and recommendations for the 2nd Watch List

The surface water Watch List (WL) under the Water Framework Directive (WFD) is a mechanism for obtaining high-quality Union-wide monitoring data on potential water pollutants for the purpose of determining the risk they pose and thus whether Environmental Quality Standards (EQS) should be set for them at EU level. According to the EQS Directive (article 8b) , this list should be updated every 2 years. The main objectives of this report are: • To present an overview of the data gathered during the 1st year of monitoring of the 1st WL (also called WL dataset in this report), • To assess whether this WL dataset is sufficient to determine the risk posed by the WL substances, and consequently to determine whether any of these substances can be taken out of the WL, • To propose new substance(s) to be included in the second WL, using the information and results from the latest review of the list of priority substances, as well as any other relevant information available at the time of this report. The executive summary first explains the context for the assessment. Then, mirroring the report itself, it presents an overview of the WL dataset for the different WL substances, it specifies the criteria for taking substances out of the WL and the substances proposed on the basis of these criteria, and finally it presents the criteria for including new substances in the WL and the new proposed WL candidates.JRC.D.2-Water and Marine Resource

Modes of action of the current Priority Substances list under the Water Framework Directive and other substances of interest

The Water Framework Directive 2000/60/EC (WFD) has established a strategy for water protection that includes specific measures for pollution control to achieve good chemical and ecological status at European level. There is a need to review the approach to the current listing of priority substances (PS) under the WFD and to the current assessment of the chemical status, and consider eventually a wider range of chemical substances that could be covered in future monitoring programmes. Overall, the aim is to assess the water status more holistically and understand which the real effects are caused by the sum of the chemical substances present in the aquatic environment (including emerging pollutants /other substances of interest, metabolites and transformation products). The assessment of chemical status should be improved and linked with ecological status where relevant. Hundreds of different substances may co-occur, and even if most are present at very small concentrations they could exert a toxic effect on aquatic organisms (Carvalho et al. 2014) exposed for their entire life cycle and indirectly on human health (via food and drinking water consumption). Some of the substances in the current list of Priority Substances and in the first Watch List are considered in groups (e.g. brominated diphenylethers, neonicotinoid insecticides), but the overall approach to chemical pollution is otherwise based on the regulation of single substances. It has become increasingly clear that the risks from the vast number of chemical substances present in the environment cannot be adequately controlled on this basis. The Commission acknowledges the need to consider the potential toxic effects of mixtures of chemicals (EC COM(2012)252, 7th EAP). The challenge is to find a way of capturing a true picture of the chemical status of water bodies based on standards and methods that assess the presence of an adequate range of representative chemical effect types or modes of action (MoA), for example. The knowledge on the MoA is an important driver for linking exposure to chemicals to their effects in the aquatic environment, and therefore for development and application of the scientific methodologies for the assessment of combined effects of chemicals - the effect-based methods (EBM). The EBM, including biomarkers and bioassays, can target different levels of biological organisation in the aquatic environment, such as individual and/or sub-organism, community, and population levels (Carvalho et al. 2014, Ann-Sofie Wernersson et al. 2014). It is however much less clear how these EBM can be used to capture (predictively) the indirect effects that might occur in humans following long-term chronic exposure to pollutants via the aquatic environment. The use of effect-based monitoring approaches, complementary to chemical analysis, could allow assessing chemical status more holistically (rather than with a limited but ever-growing list of individual substances). The use of the EBM offers also the advantage of overcoming analytical difficulties (Kunz et al. 2015) and reducing monitoring costs by screening. To become a credible complement to chemical monitoring information, however, a better understanding of the capabilities and gaps of available EBM is needed. This report, based on a comprehensive literature study, reviews the current PS list and other substances of interest, considering their MoA(s). The review of data from the open sources clearly identified few groups of toxicological endpoints, with the majority driven by non-specific mechanisms (e.g. oxidative stress, activation of metabolizing / detoxifying pathways, histopathology, and others), and few groups with more specific biochemical / physiological pathways (photosynthesis inhibition, acetylcholinesterase inhibition, presence of PAHs metabolites, expression of metallothioneins). The majority of current PS and other substances of interest can be grouped, based on few common toxicological endpoints, and biomarkers are available for determining the concentrations and/or effects of some groups of substances. The identified biomarkers of effect seem to be however in general not very specific. There is clearly no “one size fits all” bioassay / EBM that could provide the toxicological potency of every PS and other substances of interest and their mixture toward all aquatic organisms in all water bodies, but rather a battery of bioassays that should be selected as “fit for purpose”. In addition, the present report allowed identification of uncertainty and inconsistency in observations, and thus identified areas where future investigations can be best directed. The present knowledge about MoA(s) remains limited, especially for the emerging substances of concern, such as pyrethroids and neonicotinoides.JRC.D.2-Water and Marine Resource

Community Supported Stardust Compendia

The Stardust cometary and interstellar collections present unprecedented challenges in sample preparation and analysis. The ensemble of approx.80 tracks and dozens of foil craters from the cometary collection for which we have analyses exhibits a bewildering complexity and diversity of materials. The interstellar collection is even more challenging, because of the extremely low fluence of interstellar dust, a relatively large background of secondary ejecta from impacts on the spacecraft, and the small size of interstellar dust, approximately three orders of magnitude smaller in mass than typical cometary particles. Unlike with the other returned sample collections, characterization of these samples beyond basic photo-documentation is not generally practical at JSC. Even among the other small-particle collections, currently the cosmic dust and Hayabusa samples, SEM/EDX can provide basic chemistry. This is not possible with Stardust particles without destructive and invasive sample preparation. Furthermore, SEM/EDX requires isolating small grains from adhering aerogel. A reliable technique to carry out this task does not exist. Complete characterization of particles requires coordinated analyses using synchrotron and electron-beam microprobes, which do not exist at any one lab. Thus, it was recognized since the Stardust Preliminary Examination in 2006 that characterization of the samples would rely on the worldwide community of Stardust Investigators. Here we announce the development of community-editable, wiki-style Stardust compendia that will support this effort. Our intention is that this will facilitate sample requests by providing basic characterization of tracks. We expect that this will also support comprehensive meta-analyses (global syntheses of analyses) of the collections

Analytical methods for substances in the Watch List under the Water Framework Directive

The JRC organised in March 2018 a technical workshop on the analysis of the existing and the three new watch list (WL) substances of the Water Framework Directive (WFD) in order to share experience and knowledge on analytical methods and to identify the obstacles to reaching the environmental quality standards (EQS) or predicted no effect concentrations (PNEC). The results from the first year of monitoring the substances of the 1st WL showed that some countries have found it very difficult to reach a satisfactory analytical limit of quantification (LOQ) for five out of the 17 substances (17-alpha-ethinylestradiol (EE2), 17-beta-estradiol (E2), azithromycin, imidacloprid, and methiocarb). The most difficult WL substance to analyse is EE2 with its very low EQS value of 0.035 ng/L. Five countries have reported for EE2 LOQs ≤ EQS, and other four countries a close LOQ (0.05 - 0.1 ng/L). However, the workshop participants (experts from Member States and Island, Switzerland and Turkey) stressed that the analysis of EE2 at ultra trace levels is complicated and work intensive because a good clean-up procedure and a very clean and sensitive LC-MS/MS instrument are necessary. The analytical methods for the three new WL substances amoxicillin, ciprofloxacin, and metaflumizone were discussed at the workshop and optimized methods for the water sample preservation and analysis for them, based on solid-phase extraction (SPE) followed by liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) analysis, are presented in this report. The workshop showed that many Member States (MS) are using today direct LC-MS/MS injection techniques. Direct LC-MS/MS injection should however only be performed for water soluble substances with low KOW and Kd(sed) values for which partitioning to suspended particulate matter (SPM) can be neglected. A literature study revealed that EE2 and E2 are strongly adsorbed to particulate matter and therefore have to be analysed in whole water samples. Moreover, around 20 % of ciprofloxacin is present in the particulate water phase. Therefore, analysis of the dissolved water phase by direct LC-MS/MS injection could deliver for this substance acceptable results similar to whole water analysis. However, an experimental analysis should be performed to confirm the comparability. Finally, some MS asked to specify in detail the different methods for the determination or calculation of the Limit of Quantification (LOQ), because the available general guidelines are not sufficient for a uniform approach. It remained unclear whether the LOQs of the presented methods are derived from appropriate real surface water samples with or without standard addition, or from calibration curves. For a better harmonisation of the methods, a consensus on the determination of the LOQ is necessary, which needs a thorough discussion on the minimum requirements for sample preparation and analysis, i.e. representative surface water matrix, standard addition, recovery, reproducibility, and multiplication factor.JRC.D.2-Water and Marine Resource

State of the art on the contribution of water to antimicrobial resistance

The antimicrobial resistance (AMR) is defined as the ability of microorganisms to withstand the effects of antibiotics and is considered a universal threat to humans, animals and the environment. The resistance mechanisms developed by bacteria originate from either the overuse of antibiotics in medical care and animal farming or from the spread of resistant genes among microorganisms. Worldwide, 700.000 people die annually from resistant infections and this means that if no action is taken, the estimated annual deaths attributable to AMR will be 10 million by 2050. The aim of this report is to discuss the mechanisms of antibiotic action and antibiotic resistance focusing on potential effects in water. Waterbodies have been indeed recognised as a significant reservoir of antibiotics and antibiotic resistance genes (ARG). They contribute to the interchange of resistance genes between pathogenic and non-pathogenic bacteria and they may favour the maintenance of the resistance in the environment. In this report, a review of the global scientific literature was conducted to show the levels of antibiotics in waste water treatment plants (WWTP), surface waters, agricultural runoff and drinking waters The most frequently monitored antibiotics in WWTP were sulfamethoxazole, ciprofloxacin and trimethoprim, while the most important substances in surface waters were erythromycin, sulfamethoxazole, trimethoprim and sulfamethazine.In parallel, a European database has been consulted to identify the antibiotics monitored in inland surface waters and the co-occurrence of heavy metals and antibiotic resistance in bacteria is discussed. It is indeed known that the chemical environmental pollution caused by heavy metals like silver (Ag), copper (Cu) or zinc (Zn) can co-select for antibiotic resistance. Antibiotics have been frequently detected in different aquatic environments within urban water cycles (waste, surface and drinking water) and, even if the levels are low (in the range of ng/L to µg/L), they could promote the acquisition of resistance by gene transfer between bacteria. The spread of AMR may be however constrained if general safety measures are taken to improve the effectiveness of wastewater treatment processes and to control the use of antibiotics in animal husbandry and in human medical practices. Additionally, new research must be conducted to understand the relationship between antibiotics’ concentration and the selection of resistance determinants in order to experimentally define the minimal concentration of antibiotics (as single and mixture) that induces resistance in bacteria. This factor should be then also considered in the evaluation of the risk assessment of antibiotics in water in order to define their environmental impactJRC.D.2-Water and Marine Resource

EU Wide Monitoring Survey on Waste Water Treatment Plant Effluents

In the year 2010, effluents from 90 European waste water treatment plants (WWTPs) were collected and analysed in total for 160 organic chemicals and 20 inorganic trace elements. The analyses were complemented by applying also effect-based monitoring approaches aiming at estrogenicity and dioxin-like toxicity analysed by in vitro reporter gene bioassays, and yeast and diatom culture acute toxicity optical bioassays. The analytical work was performed in six European expert laboratories. This European-wide monitoring study on the occurrence of micropollutants in WWTP effluents represents the largest EU wide monitoring survey on WWTP effluents ever performed. It produced a comprehensive data set on many so far only locally investigated “emerging” compound classes including pharmaceuticals and personal care products (PPCPs), veterinary (antibiotic) drugs, perfluoroalkyl substances (PFASs), organophosphate ester flame retardants, pesticides (and some metabolites) or industrial chemicals such as benzotriazoles (corrosion inhibitors), polycyclic musk fragrances, x-ray contrast agents, Gadolinium compounds, and siloxanes. The obtained results show the presence of 131 target organic compounds in European wastewater effluents, in concentrations ranging from low nanograms to milligrams per liter. These results obtained from 90 different European WWTPs allow the calculation of a European median level for the chemicals investigated. The most relevant compounds identified in the effluent water samples in terms of frecquency of detection, maximum, average and median concentration levels were Sucralose, Acesulfame K (artificial sweeteners), PFOA, PFHxA, PFHpA, PFOS (perfluoroalkyl substances), N,N’-Diethyltoluamide (DEET; insect repellent), Benzotriazoles (corrosion inhibitors), the pharmaceuticals Bisoprolol, Carbamazepine, Ciprofloxacine, Citaprolam, Clindamycine, Codeine, Diltiazem, Diphenhydramin, Eprosartan, Fexofenadine, Flecainide, Gemfibrozil, Fluconazole, Haloperidol, Ibersartan, Ibuprofen, Ketoprofen, Oxazepam, Risperidone, Sulfamethoxazole, Telmisartan, Tramadol, Trimethoprim, Venlafaxin, the organo-phosphate ester flame retardants Tri-iso-butylphosphate (TIBP), Tributylphosphate (TBP), Tris(2-chloroethyl)phosphate (TCEP), Tris(2-chloroisopropyl)phosphate (TCPP), Tris(2-butoxyethyl)phosphate (TDCP), Tris(2-butoxyethyl)phosphate (TBEP), Triphenyl-phosphate (TPP), 2-Ethylhexyldiphenyl-phosphate (EHDPP), the x-ray contrast media Amidotrizoic acid, Iohexol, Iopromid, Iomeprol, Iopamidol, the pesticides Terbutylazine, Terbutylazine-desethyl (metabolite), MCPA, Mecoprop, Diuron, Triclosan (antibacterial), and Gadolinium (from magnetic resonance imaging contrast media used in hospitals).JRC.H.1-Water Resource

Primary hepatic lymphoma presenting as fulminant hepatic failure with hyperferritinemia: A case report

<p>Abstract</p> <p>Introduction</p> <p>Primary hepatic lymphoma is an unusual form of non-Hodgkin's lymphoma that usually presents with constitutional symptoms, hepatomegaly and signs of cholestatic jaundice. Diffuse hepatic infiltration is uncommon and presentation with acute hepatic failure even more rare. The presence of markedly elevated ferritin levels can complicate the evaluation process and suggest alternative diagnoses.</p> <p>We present the case of a middle-aged woman exhibiting pancytopenia, hyperferritinemia and rapidly deteriorating to develop acute hepatic failure. Her initial clinical picture led to a working diagnosis of adult onset Still's disease with probable hemophagocytic syndrome before her worsening liver function necessitated a percutaneous liver biopsy and establishment of the final diagnosis of primary hepatic lymphoma.</p> <p>Conclusion</p> <p>Primary hepatic lymphoma is an uncommon malignancy and its manifestation as progressive hepatitis or acute fulminant hepatic failure can be difficult to diagnose. The presence of constitutional symptoms, pancytopenia and high ferritin levels can complicate the evaluation process. A liver biopsy early in the course of liver dysfunction may establish the diagnosis without a higher risk of bleeding complications seen once liver failure sets in.</p

“Dogged” Search of Fresh Nakhla Surfaces Reveals New Alteration Textures

Special Issue: 74th Annual Meeting of the Meteoritical Society, August 8-12, 2011, London, U.K.International audienceCarbonaceous chondrites are considered as amongst the most primitive Solar System samples available. One of their primitive characteristics is their enrichment in volatile elements.This includes hydrogen, which is present in hydrated and hydroxylated minerals. More precisely, the mineralogy is expected to be dominated by phyllosilicates in the case of CM chondrites, and by Montmorillonite type clays in the case of CI. Here, in order to characterize and quantify the abundance of lowtemperature minerals in carbonaceous chondrites, we performed thermogravimetric analysis of matrix fragments of Tagish Lake, Murchison and Orgueil

Spin-orbit coupling induced Van Hove singularity in proximity to a Lifshitz transition in Sr4Ru3O10

Funding: CAM, MN and PW gratefully acknowledge funding from the Engineering and Physical Sciences Research Council through EP/R031924/1 and EP/S005005/1, IB through the International Max Planck Research School for Chemistry and Physics of Quantum Materials and LCR from a fellowship from the Royal Commission of the Exhibition of 1851. RA, RF and AV thank the EU’s Horizon 2020 research and innovation program under Grant Agreement No. 964398 (SUPERGATE).Van Hove singularities (VHss) in the vicinity of the Fermi energy often play a dramatic role in the physics of strongly correlated electron materials. The divergence of the density of states generated by VHss can trigger the emergence of new phases such as superconductivity, ferromagnetism, metamagnetism, and density wave orders. A detailed understanding of the electronic structure of these VHss is therefore essential for an accurate description of such instabilities. Here, we study the low-energy electronic structure of the trilayer strontium ruthenate Sr4Ru3O10, identifying a rich hierarchy of VHss using angle-resolved photoemission spectroscopy and millikelvin scanning tunneling microscopy. Comparison of k-resolved electron spectroscopy and quasiparticle interference allows us to determine the structure of the VHss and demonstrate the crucial role of spin-orbit coupling in shaping them. We use this to develop a minimal model from which we identify a new mechanism for driving a field-induced Lifshitz transition in ferromagnetic metals.Peer reviewe