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      Is Open Access

      Current EU research activities on combined exposure to multiple chemicals

      review-article
      a , * , b , c , d , e , f , g , h , a , i , j , k , i , l , m , h , f , n , o , p , q , f , r
      Environment International
      Elsevier Science
      AO, adverse outcome, AOP, adverse outcome pathway, BMD, benchmark dose modelling, BQE, biological quality element, CA, concentration addition, CAG, cumulative assessment group, CMEP, chemical monitoring and emerging pollutants, CRA, cumulative risk assessment, DART, developmental and reproductive toxicity, DEB, dynamic energy budget, EBT, effect-based tools, EDC, endocrine disrupting chemical, EQS, environmental quality standard, HBM, human biomonitoring, IA, independent action, IATA, integrated approach to testing and assessment, IPRA, integrated probabilistic risk assessment, iPSC, induced pluripotent stem cells, LOE, lines of evidence, MCR, maximum cumulative ratio, MCRA, Monte Carlo risk assessment tool, MEC, measured exposure concentration, MoA, mode of action, MRA, mixture risk assessment, MSFD, Marine Strategy Framework Directive, NAM, new approach methodology, PBTK, physiologically based toxicokinetic (model), PEC, predicted exposure concentration, PNEC, predicted no effect concentration, QSAR, quantitative structure activity relationship, RDT, repeated dose systemic toxicity, TK, toxicokinetic, SMRI, similar mixture risk indicator, SYRINA, systematic review and integrated assessment, TTC, Threshold of Toxicological Concern, WFD, Water Framework Directive

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          Abstract

          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.

          Highlights

          • 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

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          Most cited references63

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          Organic chemicals jeopardize the health of freshwater ecosystems on the continental scale.

          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.
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            Nontarget Screening with High Resolution Mass Spectrometry in the Environment: Ready to Go?

            The vast, diverse universe of organic pollutants is a formidable challenge for environmental sciences, engineering, and regulation. Nontarget screening (NTS) based on high resolution mass spectrometry (HRMS) has enormous potential to help characterize this universe, but is it ready to go for real world applications? In this Feature article we argue that development of mass spectrometers with increasingly high resolution and novel couplings to both liquid and gas chromatography, combined with the integration of high performance computing, have significantly widened our analytical window and have enabled increasingly sophisticated data processing strategies, indicating a bright future for NTS. NTS has great potential for treatment assessment and pollutant prioritization within regulatory applications, as highlighted here by the case of real-time pollutant monitoring on the River Rhine. We discuss challenges for the future, including the transition from research toward solution-centered and robust, harmonized applications.
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              Regulate to reduce chemical mixture risk

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                Author and article information

                Contributors
                Journal
                Environ Int
                Environ Int
                Environment International
                Elsevier Science
                0160-4120
                1873-6750
                1 November 2018
                November 2018
                : 120
                : 544-562
                Affiliations
                [a ]European Commission, Directorate General Joint Research Centre, Directorate F – Health, Consumers and Reference Materials, Ispra, Italy
                [b ]INSERM UMR-S 1124, Université Paris Descartes, Paris, France
                [c ]Helmholtz Centre for Environmental Research – UFZ, Leipzig, Germany
                [d ]European Commission, Directorate General Joint Research Centre, Directorate B – Growth and Innovation, Ispra, Italy
                [e ]Scientific Committee and Emerging Risks Unit, European Food Safety Authority (EFSA), Parma, Italy
                [f ]Swetox, Karolinska Institutet, Unit of Toxicology Sciences, Södertälje, Sweden
                [g ]Faust & Backhaus Environmental Consulting, Bremen, Germany
                [h ]European Commission, Directorate General Research and Innovation, Directorate E – Health, Brussels, Belgium
                [i ]National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
                [j ]German Environment Agency, UBA, Berlin, Germany
                [k ]Institute for Environment, Health and Societies, Brunel University, Uxbridge, United Kingdom
                [l ]Institute of Risk Assessment Sciences – IRAS, Utrecht University, Utrecht, the Netherlands
                [m ]European Commission, Directorate General Joint Research Centre, Directorate D – Sustainable Resources, Ispra, Italy
                [n ]Pesticides Unit, European Food Safety Authority (EFSA), Parma, Italy
                [o ]European Environment Agency, Copenhagen, Denmark
                [p ]Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands
                [q ]Deltares, Delft, the Netherlands
                [r ]School of Science and Technology, MTM, Örebro University, Örebro, Sweden
                Author notes
                [* ]Corresponding author at: European Commission, Directorate General Joint Research Centre, Directorate F – Health, Consumers and Reference Materials, Chemical Safety and Alternative Methods Unit (F.3), Via E. Fermi, 2749, TP126, I-21027 Ispra, VA, Italy. stephanie.bopp@ 123456ec.europa.eu
                Article
                S0160-4120(18)30842-0
                10.1016/j.envint.2018.07.037
                6192826
                30170309
                80d600c0-a545-477b-ac76-0573da907bd2
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 4 May 2018
                : 25 July 2018
                : 26 July 2018
                Categories
                Article

                ao, adverse outcome,aop, adverse outcome pathway,bmd, benchmark dose modelling,bqe, biological quality element,ca, concentration addition,cag, cumulative assessment group,cmep, chemical monitoring and emerging pollutants,cra, cumulative risk assessment,dart, developmental and reproductive toxicity,deb, dynamic energy budget,ebt, effect-based tools,edc, endocrine disrupting chemical,eqs, environmental quality standard,hbm, human biomonitoring,ia, independent action,iata, integrated approach to testing and assessment,ipra, integrated probabilistic risk assessment,ipsc, induced pluripotent stem cells,loe, lines of evidence,mcr, maximum cumulative ratio,mcra, monte carlo risk assessment tool,mec, measured exposure concentration,moa, mode of action,mra, mixture risk assessment,msfd, marine strategy framework directive,nam, new approach methodology,pbtk, physiologically based toxicokinetic (model),pec, predicted exposure concentration,pnec, predicted no effect concentration,qsar, quantitative structure activity relationship,rdt, repeated dose systemic toxicity,tk, toxicokinetic,smri, similar mixture risk indicator,syrina, systematic review and integrated assessment,ttc, threshold of toxicological concern,wfd, water framework directive

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