Increased synthetic chemical production and diversification in developing countries caused serious aquatic pollution worldwide with emerging organic pollutants (EOPs) detected in surface water rising ...health concerns to human and aquatic ecosystem even at low ng/L concentration with long-term exposure. The Yangtze River Delta (YRD) area serves agriculture and industry for people in eastern China. However, the current knowledge on the occurrence and ecological risk of diverse EOPs which are present in the aquatic environment is limited. This study was to investigate the complexity and diversity of EOPs in surface water from 28 sampling sites, which were selected to represent urban, industrial or agriculture areas in the YRD area. In total 484 chemicals were analyze by a target screening approach using liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS). 181 out of 484 EOPs were detected at least one site in the YRD area, and 44 analytes, mostly industrial chemicals and pesticides, were ubiquitous at all sampling sites. Most EOPs were industrial chemicals with 1H-benzotriazole and organophosphate flame retardants (PFRs) as the chemicals with highest concentrations. For 21 pesticides, mostly herbicides, maximum concentrations of atrazine and isoproturon were above the annual average environmental quality standards of Europe. Amantadine and DEET were the dominant pharmceuticals and personal care products (PPCPs) in the YRD area. Compared to urban areas (mostly in Qinhuai River), chemical profiles from industrial areas were more complex. Industrial activities likely have a strong impact on the composition of chemical mixtures in surface water from the YRD area. ISO E Super, 4-methylbenzylidene camphor and clotrimazole detected in this study are potentially persistent and bioaccumulative chemicals. Furthermore, results of risk assessment showed that hazard quotients of dimethyldioctadecylammonium, didecyldimethylammonium and octocrylene were higher than one and occur frequently, which indicates possibly adverse effects on fish species in the YRD area.
Display omitted
•The surface waters in the YRD area are polluted with a vast range of predominantly industrial EOPs.•44 EOPs detected in surface water from YRD area everywhere, most of them were industrial chemicals and pesticides.•ISO E Super, 4-methylbenzylidene camphor and clotrimazole are potential persistent and bioaccumulative chemicals.•Dimethyldioctadecylammonium, didecyldimethylammonium and octocrylene show high risks to aquatic organisms.
Wastewater effluents, groundwater, surface water, sediments, soils and air particulate matter are often contaminated by a multitude of chemicals. Since often no a priori knowledge of relevant ...toxicants exists, chemical analysis alone is not an appropriate tool for hazard assessment. Instead, a linkage of effect data and hazardous compounds is required. For that purpose, effect-directed analysis (EDA) was developed, which is based on a combination of biotesting, fractionation procedures and chemical analytical methods. Since a controversial discussion about the prospects of success in relation to the expense exists, the current methodological state of EDA for organic toxicants in complex mixtures and important results are reviewed in this paper with the aim of establishing criteria for the successful use of this promising tool. While EDA is a powerful tool to identify specifically acting individual toxicants close to the source of emission, it is inappropriate for screening purposes and often may fail in remote areas where the concentrations of specific toxicants are too low relative to the nonspecific toxicity of the whole mixture of natural and anthropogenic compounds. The biological tools have to be carefully selected with respect to their ability to detect specific effects and their significance in hazard assessment. Sophisticated chemical tools are required to identify individual toxicants in mixtures of thousands of compounds, which are typical for contaminated environments.
To detect site-specific, suspected and formerly unknown contaminants in a wastewater treatment plant effluent, we established a screening procedure based on liquid chromatography–high resolution mass ...spectrometry (LC–HRMS) with stepwise identification schemes. Based on automated substructure searches a list of 2160 suspected site-specific and documented water contaminants was reduced to those amenable to LC–HRMS. After searching chromatograms for exact masses of suspects, presumably false positive detections were stepwise excluded by retention time prediction, the evaluation of isotope patterns, ionization behavior, and HRMS/MS spectra. In nontarget analysis, peaks for identification were selected based on distinctive isotope patterns and intensity. The stepwise identification of nontarget compounds was automated by a plausibility check of molecular formulas using the Seven Golden Rules, an exclusion of compounds with presumably low commercial importance and an automated HRMS/MS evaluation. Six suspected and five nontarget chemicals were identified, of which two have not been previously reported as environmental pollutants.
•A LC–HRMS-based suspect and nontarget screening was applied to wastewater.•Manual data processing to identify candidate structures was accelerated by automated software-based procedure.•Identification was supported by sophisticated analytical methods such as deuterium exchange.•Eleven site-specific and formerly unknown compounds were identified.•We provide a framework to extend analytical procedures from target to suspect and nontarget compounds.
A screening procedure based on liquid chromatography–high resolution mass spectrometry (LC–HRMS) with a systematic data evaluation was established, which allowed detecting suspected and formerly unknown contaminants in wastewater.
Macrophages are important target cells for the Human Immunodeficiency Virus Type I (HIV-1) in vivo. Several studies have assessed the molecular biology of the virus in this cell type, and a number of ...differences towards HIV-1 infection of CD4+ T cells have been described. There is a broad consensus that macrophages resist HIV-1 infection much better than CD4+ T cells. Among other reasons, this is due to the presence of the recently identified host cell restriction factor SamHD1, which is strongly expressed in cells of the myeloid lineage. Furthermore, macrophages produce and release relatively low amounts of infectious HIV-1 and are less sensitive to viral cytotoxicity in comparison to CD4+ T cells. Nevertheless, macrophages play a crucial role in the different phases of HIV-1 infection. In this review, we summarize and discuss the significance of macrophages for HIV-1 transmission, the acute and chronic phases of HIV-1 infection, the development of acquired immunodeficiency syndrome (AIDS) and HIV-associated diseases, including neurocognitive disorders. We propose that interaction of HIV-1 with macrophages is crucial during all stages of HIV-1 infection. Thus, long-term successful treatment of HIV-1 infected individuals requires potent strategies to prevent HIV-1 from entering and persisting in these cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 ...(SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions.
Organic chemicals can contribute to local and regional losses of freshwater biodiversity and ecosystem services. However, their overall relevance regarding larger spatial scales remains unknown. ...Here, we present, to our knowledge, the first risk assessment of organic chemicals on the continental scale comprising 4,000 European monitoring sites. Organic chemicals were likely to exert acute lethal and chronic long-term effects on sensitive fish, invertebrate, or algae species in 14% and 42% of the sites, respectively. Of the 223 chemicals monitored, pesticides, tributyltin, polycyclic aromatic hydrocarbons, and brominated flame retardants were the major contributors to the chemical risk. Their presence was related to agricultural and urban areas in the upstream catchment. The risk of potential acute lethal and chronic long-term effects increased with the number of ecotoxicologically relevant chemicals analyzed at each site. As most monitoring programs considered in this study only included a subset of these chemicals, our assessment likely underestimates the actual risk. Increasing chemical risk was associated with deterioration in the quality status of fish and invertebrate communities. Our results clearly indicate that chemical pollution is a large-scale environmental problem and requires far-reaching, holistic mitigation measures to preserve and restore ecosystem health.
•Multiple exposures and their combined effects require better risk management.•Precautionary approaches and intermediate measures could already be applied.•A European strategy is needed to address ...the research and policy needs.
The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages:•We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures.•Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors.•Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps.•A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient.
Humans and wildlife are exposed to an intractably large number of different combinations of chemicals via food, water, air, consumer products, and other media and sources. This raises concerns about ...their impact on public and environmental health. The risk assessment of chemicals for regulatory purposes mainly relies on the assessment of individual chemicals. If exposure to multiple chemicals is considered in a legislative framework, it is usually limited to chemicals falling within this framework and co-exposure to chemicals that are covered by a different regulatory framework is often neglected. Methodologies and guidance for assessing risks from combined exposure to multiple chemicals have been developed for different regulatory sectors, however, a harmonised, consistent approach for performing mixture risk assessments and management across different regulatory sectors is lacking. At the time of this publication, several EU research projects are running, funded by the current European Research and Innovation Programme Horizon 2020 or the Seventh Framework Programme. They aim at addressing knowledge gaps and developing methodologies to better assess chemical mixtures, by generating and making available internal and external exposure data, developing models for exposure assessment, developing tools for in silico and in vitro effect assessment to be applied in a tiered framework and for grouping of chemicals, as well as developing joint epidemiological-toxicological approaches for mixture risk assessment and for prioritising mixtures of concern. The projects EDC-MixRisk, EuroMix, EUToxRisk, HBM4EU and SOLUTIONS have started an exchange between the consortia, European Commission Services and EU Agencies, in order to identify where new methodologies have become available and where remaining gaps need to be further addressed. This paper maps how the different projects contribute to the data needs and assessment methodologies and identifies remaining challenges to be further addressed for the assessment of chemical mixtures.
•Mapping EU funded research projects to different aspects of mixture risk assessment.•Overview of current status and methodological developments•Need to further address data and knowledge gaps overarching different chemical sectors
Effect-based methods including cell-based bioassays, reporter gene assays and whole-organism assays have been applied for decades in water quality monitoring and testing of enriched solid-phase ...extracts. There is no common EU-wide agreement on what level of bioassay response in water extracts is acceptable. At present, bioassay results are only benchmarked against each other but not against a consented measure of chemical water quality. The EU environmental quality standards (EQS) differentiate between acceptable and unacceptable surface water concentrations for individual chemicals but cannot capture the thousands of chemicals in water and their biological action as mixtures. We developed a method that reads across from existing EQS and includes additional mixture considerations with the goal that the derived effect-based trigger values (EBT) indicate acceptable risk for complex mixtures as they occur in surface water. Advantages and limitations of various approaches to read across from EQS are discussed and distilled to an algorithm that translates EQS into their corresponding bioanalytical equivalent concentrations (BEQ). The proposed EBT derivation method was applied to 48 in vitro bioassays with 32 of them having sufficient information to yield preliminary EBTs. To assess the practicability and robustness of the proposed approach, we compared the tentative EBTs with observed environmental effects. The proposed method only gives guidance on how to derive EBTs but does not propose final EBTs for implementation. The EBTs for some bioassays such as those for estrogenicity are already mature and could be implemented into regulation in the near future, while for others it will still take a few iterations until we can be confident of the power of the proposed EBTs to differentiate good from poor water quality with respect to chemical contamination.
Display omitted
•Effect-based triggers (EBTs) for bioassays discriminate good from poor water quality.•EBTs can be derived by read across from existing water quality guideline values.•Mixture factor warranted for bioassays responding to many different chemicals.•EBT derivation method applicable to every bioassay subject to data availability•Here we derived preliminary EBTs for 32 bioassays and discuss many more.
Display omitted
•366 chemicals detected in 56 European WWTP effluents at <1 ng/L to >100 µg/L.•Three different risk metrics (RQ, HU, TU) provided complementary information.•293 mixture components of ...concern exceeded the risk threshold.•32 consensus mixture risk contributors of high concern identified.•Activated carbon and ozonation treatments reduced toxic risks below thresholds.
In this study, 56 effluent samples from 52 European wastewater treatment plants (WWTPs) were investigated for the occurrence of 499 emerging chemicals (ECs) and their associated potential risks to the environment. The two main objectives were (i) to extend our knowledge on chemicals occurring in treated wastewater, and (ii) to identify and prioritize compounds of concern based on three different risk assessment approaches for the identification of consensus mixture risk drivers of concern. Approaches include (i) PNEC and EQS-based regulatory risk quotients (RQs), (ii) species sensitivity distribution (SSD)-based hazard units (HUs) and (iii) toxic units (TUs) for three biological quality elements (BQEs) algae, crustacean, and fish.
For this purpose, solid-phase extracts were analysed with wide-scope chemical target screening via liquid chromatography high-resolution mass spectrometry (LC-HRMS), resulting in 366 detected compounds, with concentrations ranging from < 1 ng/L to > 100 µg/L. The detected chemicals were categorized with respect to critical information relevant for risk assessment and management prioritization including: (1) frequency of occurrence, (2) measured concentrations, (3) use groups, (4) persistence & bioaccumulation, and (5) modes of action. A comprehensive assessment using RQ, HU and TU indicated exceedance of risk thresholds for the majority of effluents with RQ being the most sensitive metric. In total, 299 out of the 366 compounds were identified as mixture risk contributors in one of the approaches, while 32 chemicals were established as consensus mixture risk contributors of high concern, including a high percentage (66%) of pesticides and biocides. For samples which have passed an advanced treatment using ozonation or activated carbon (AC), consistently much lower risks were estimated.
PDF
