Assessment of the use of substances in hydraulic fracturing of shale gas reservoirs under REACH

Hydraulic fracturing is a technique that has been applied for stimulation of conventional oil and gas wells in the US since many years. The recent developments in high volume hydraulic fracturing combined with directional/horizontal drilling techniques have made the gas trapped into unconventional reservoirs such as shale formations economically exploitable. In the US, shale gas has become an important energy resource. In the EU, there is limited experience in the use of these techniques and research/experimental drilling activities have been performed in some Member States where shale gas reservoirs are present. In this context, the EC's Joint Research Centre’s Institute for Health and Consumer Protection (JRC-IHCP) was asked by EC's DG Environment to perform an assessment of REACH registration dossiers of certain selected substances that may be connected with the use in hydraulic fracturing of shale gas reservoirs. The main goal of this task was to understand whether this type of use has been registered under REACH and eventually how industry is dealing with related exposure scenarios and exposure assessments. The present document reports and discusses the results of the analysis of the selected REACH registration dossiers.JRC.I.4-Nanobioscience

NANoREG harmonised terminology for environmental health and safety assessment of nanomaterials

Several terms in the field of environmental health and safety (EHS) assessment of chemicals and nanomaterials (hereinafter NMs) have been defined or used by the scientific community and different organisations, including international bodies, European authorities, and industry associations. This is also true for multidisciplinary projects such as NANoREG, which aims at supporting regulatory authorities and industry in dealing with EHS issues of manufactured NMs. The objective of the present JRC technical report is to publish the harmonised terminology that has been developed and used within NANoREG. It has been agreed upon and adopted by all project partners in their activities and related documents. The report specifically includes: i) the methodology used to select key terms that form the harmonised terminology and to develop harmonised definitions; ii) the existing literature definitions that have been used as a starting point to develop for each key term a harmonised definition; and iii) the reason(s) behind the choices that have been made in drafting a definition. As far as possible, the harmonised definition is reproducing (an) already existing definition text(s), thus avoiding the creation of new and unwelcome information. The discussion on the key terms to be considered for the harmonised terminology led to the selection of 43 key terms. The list includes terms with international regulatory relevance, such as those defined at OECD level, as well as terms that have a specific meaning and use under REACH. The 'NANoREG Harmonised Terminology' has already proven very useful in the context of the OECD work, as support document to the April 2016 OECD Expert Meeting on 'Grouping and read-across for the hazard assessment of manufactured nanomaterials', and in a regulatory context, as support document to the work recently released by RIVM, ECHA and JRC on using (eco)toxicological data for bridging data gaps between nanoforms of the same substance (March 2016). For quick access, the 'NANoREG Harmonised Terminology' is reported in Section 3.JRC.I.4-Nanobioscience

Mapping Nanomedicine Terminology in the Regulatory Landscape

A common terminology is essential in any field of science and technology for a mutual understanding among different communities of experts and regulators, harmonisation of policy actions, standardisation of quality procedures and experimental testing, and the communication to the general public. It also allows effective revision of information for policy making and optimises research fund allocation. In particular, in emerging scientific fields with a high innovation potential, new terms, descriptions and definitions are quickly generated, which are then ambiguously used by stakeholders having diverse interests, coming from different scientific disciplines and/or from various regions. The application of nanotechnology in health -often called nanomedicine- is considered as such emerging and multidisciplinary field with a growing interest of various communities. In order to support a better understanding of terms used in the regulatory domain, the Nanomedicines Working Group of the International Pharmaceutical Regulators Forum (IPRF) has prioritised the need to map, compile and discuss the currently used terminology of regulatory scientists coming from different geographic areas. The JRC has taken the lead to identify and compile frequently used terms in the field by using web crawling and text mining tools as well as the manual extraction of terms. Websites of 13 regulatory authorities and clinical trial registries globally involved in regulating nanomedicines have been crawled. The compilation and analysis of extracted terms demonstrated sectorial and geographical differences in the frequency and type of nanomedicine related terms used in a regulatory context. Finally 31 relevant and most frequently used terms deriving from various agencies have been compiled, discussed and analysed for their similarities and differences. These descriptions will support the development of harmonised use of terminology in the future. The report provides necessary background information to advance the discussion among stakeholders. It will strengthen activities aiming to develop harmonised standards in the field of nanomedicine, which is an essential factor to stimulate innovation and industrial competitiveness.JRC.F.2-Consumer Products Safet

A Model-Based Prioritisation Exercise for the European Water Framework Directive

A model-based prioritisation exercise has been carried out for the Water Framework Directive (WFD) implementation. The approach considers two aspects: the hazard of a certain chemical and its exposure levels, and focuses on aquatic ecosystems, but also takes into account hazards due to secondary poisoning, bioaccumulation through the food chain and potential human health effects. A list provided by EU Member States, Stakeholders and Non-Governmental Organizations comprising 2,034 substances was evaluated according to hazard and exposure criteria. Then 78 substances classified as “of high concern” where analysed and ranked in terms of risk ratio (Predicted Environmental Concentration/Predicted No-Effect Concentration). This exercise has been complemented by a monitoring-based prioritization exercise using data provided by Member States. The proposed approach constitutes the first step in setting the basis for an open modular screening tool that could be used for the next prioritization exercises foreseen by the WFD

Concern-Driven Integrated Toxicity Testing Strategies for Nanomaterials - Report of the NanoSafety Cluster Working Group 10

Bringing together topic-related European Union-(EU)-funded projects, the so-called “NanoSafety Cluster” aims at identifying key areas for further research on risk assessment procedures for nanomaterials (NM). The outcome of NanoSafety Cluster Working Group 10, this commentary presents a vision for concern-driven integrated approaches for the (eco-)toxicological testing and assessment (IATA) of NM. Such approaches should start out by determining concerns, i.e. specific information needs for a given NM based on realistic exposure scenarios. Recognized concerns can be addressed in a set of tiers using standardized protocols for NM preparation and testing. Tier 1 includes determining physico-chemical properties, non-testing (e.g. structure activity relationships) and evaluating existing data. In tier 2, a limited set of in vitro and in vivo tests are performed that can either indicate that the risk of the specific concern is sufficiently known or indicate the need for further testing, including details for such testing. Ecotoxicological testing begins with representative test organisms followed by complex test systems. After each tier, it is evaluated whether the information gained permits assessing the safety of the NM so that further testing can be waived. By effectively exploiting all available information, IATA allow accelerating the risk assessment process and reducing testing costs and animal use (in line with the 3Rs principle implemented in EU Directive 2010/63/EU). Combining material properties, exposure, biokinetics, and hazard data, information gained with IATA can be used to recognize groups of NM based upon similar modes-of-action. Grouping of substances in return should form integral part of the IATA themselves

ITS-NANO - Prioritising nanosafety research to develop a stakeholder driven intelligent testing strategy

Background To assess the risk of all nanomaterials (NMs) on a case-by-case basis is challenging in terms of financial, ethical and time resources. Instead a more intelligent approach to knowledge gain and risk assessment is required. Methods A framework of future research priorities was developed from the accorded opinion of experts covering all major stake holder groups (government, industry, academia, funders and NGOs). It recognises and stresses the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling approaches as key components of the current and future risk assessment of NMs. Results The framework for future research has been developed from the opinions of over 80 stakeholders, that describes the research priorities for effective development of an intelligent testing strategy (ITS) to allow risk evaluation of NMs. In this context, an ITS is a process that allows the risks of NMs to be assessed accurately, effectively and efficiently, thereby reducing the need to test NMs on a case-by-case basis. For each of the major topics of physicochemical characterisation, exposure identification, hazard identification and modelling, key-priority research areas are described via a series of stepping stones, or hexagon diagrams structured into a time perspective. Importantly, this framework is flexible, allowing individual stakeholders to identify where their own activities and expertise are positioned within the prioritisation pathway and furthermore to identify how they can effectively contribute and structure their work accordingly. In other words, the prioritisation hexagon diagrams provide a tool that individual stakeholders can adapt to meet their own particular needs and to deliver an ITS for NMs risk assessment. Such an approach would, over time, reduce the need for testing by increasing the reliability and sophistication of in silico approaches. The manuscript includes an appraisal of how this framework relates to the current risk assessment approaches and how future risk assessment could adapt to accommodate these new approaches. A full report is available in electronic format (pdf) at http://www.nano.hw.ac.uk/research-projects/itsnano.html webcite. Conclusion ITS-NANO has delivered a detailed, stakeholder driven and flexible research prioritisation (or strategy) tool, which identifies specific research needs, suggests connections between areas, and frames this in a time-perspective

The MARINA Risk Assessment Strategy: A Flexible Strategy for Efficient Information Collection and Risk Assessment of Nanomaterials

An engineered nanomaterial (ENM) may actually consist of a population of primary particles, aggregates and agglomerates of various sizes. Furthermore, their physico-chemical characteristics may change during the various life-cycle stages. It will probably not be feasible to test all varieties of all ENMs for possible health and environmental risks. There is therefore a need to further develop the approaches for risk assessment of ENMs. Within the EU FP7 project Managing Risks of Nanoparticles (MARINA) a two-phase risk assessment strategy has been developed. In Phase 1 (Problem framing) a base set of information is considered, relevant exposure scenarios (RESs) are identified and the scope for Phase 2 (Risk assessment) is established. The relevance of an RES is indicated by information on exposure, fate/kinetics and/or hazard; these three domains are included as separate pillars that contain specific tools. Phase 2 consists of an iterative process of risk characterization, identification of data needs and integrated collection and evaluation of data on the three domains, until sufficient information is obtained to conclude on possible risks in a RES. Only data are generated that are considered to be needed for the purpose of risk assessment. A fourth pillar, risk characterization, is defined and it contains risk assessment tools. This strategy describes a flexible and efficient approach for data collection and risk assessment which is essential to ensure safety of ENMs. Further developments are needed to provide guidance and make the MARINA Risk Assessment Strategy operational. Case studies will be needed to refine the strategy

A framework for grouping and read-across of nanomaterials- supporting innovation and risk assessment

According to some legislation grouping can streamline data gap filling for the hazard assessment of substances. The GRACIOUS Framework aims to facilitate the application of grouping of nanomaterials or nanoforms (NFs), in a regulatory context and to support innovation. This includes using grouping to enable read-across from (a) source(s), for which data and information exist, to a similar target NF where information is lacking. The Framework provides an initial set of hypotheses for the grouping of NFs which take into account the identity and use(s) of the NFs, as well as the purpose of grouping. Initial collection of basic information allows selection of an appropriate pre-defined grouping hypothesis and a tailored Integrated Approach to Testing and Assessment (IATA), designed to generate new evidence to support acceptance or rejection of the hypothesis. Users needing to develop their own user-defined hypothesis (and IATA) are also supported by the Framework. In addition, the IATA guides acquisition of the information needed to support read-across. This approach gathers information to render risk assessment more efficient, affordable, as well as reducing the use of test animals

Workshop on Regulatory Preparedness for Innovation in Nanotechnology

This report summarises the presentations and discussions at the first NanoReg2 Workshop on Regulatory Preparedness for Innovation in Nanotechnology held in Ispra, Italy 5 to 6 October 2017 and attended by approximately 60 regulators, industry representatives and other stakeholders. NanoReg2 is a European Union (EU) Horizon 2020 project. At the workshop, Regulatory Preparedness was defined as the regulators' timely awareness of innovations and the regulator's actions to check whether present legislation covers all safety aspects of each innovation, including initiating revision of the legislation as appropriate. Regulatory Preparedness, and Safe-by-Design (SbD) jointly constitute the NanoReg2 Safe Innovation Approach (SIA) for developing innovative products based on nanotechnology. The workshop aimed to gather views and identify current practices in regulatory work on safety of innovative products, tools already in use or needed, and potential difficulties in implementing Regulatory Preparedness in the EU. Presentations addressed the current state of the safety of nanotechnology innovation. The viewpoints included the regulatory framework, the principles behind it and the agencies and authorities enforcing it; nanosafety research projects and their support system (e.g. the current EU Horizon 2020 Framework Programme); national nanosafety initiatives; and the development of tools, such as foresight tools and harmonised test guidelines by the OECD for data generation. The workshop served to generate ideas for achieving Regulatory Preparedness. The participants recognised that while regulators deal with the safety of innovations, only few systematic approaches to this work exist. Some innovative products may reach the market before their safety has been appropriately assessed, as illustrated by RAPEX, the Rapid Exchange of Information System. A continuous and proactive combination of interconnected activities was considered to be required for ensuring Regulatory Preparedness. Thus, anticipation, e.g. horizon scanning, was seen as important, as was communication between regulators, innovators (industry) and other stakeholders. Regulators need to become aware of innovative products under development to ensure that the legislation and methods for safety assessment are available and adequate. Innovators must be aware of regulatory requirements and their likely development. This mutual awareness helps to develop safe products and to avoid delays or other problems in obtaining market approval. Awareness can be achieved through communication, which requires trust, e.g. promoted via "trusted environments" for confidential inquiries and information sharing. Furthermore, regulators need early access to the existing information and data relevant to safety assessment of innovative products to provide timely guidance and advice to Industry as well as to develop strategies for dealing with uncertainty, e.g. by applying the precautionary principle. Regulatory Preparedness was discussed as part of the SIA, and a "road map" of actions was suggested and outlined. The workshop has thus contributed towards acceptance of implementing Regulatory Preparedness for innovation in nanotechnology through the participation of a variety of stakeholders. This paves the way for a better dialogue among stakeholders in a fast economic development cycle, where it is even more important to quickly identify emerging needs for new approaches to regulatory issues for innovationJRC.F.2-Consumer Products Safet

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements