Bridging Across Methods in the Biosciences

Cross-disciplinary research is essential if science is to properly address societal needs. In spite of several policy initiatives to foster such research across sectors, there is still a high level of compartmentalisation in the biosciences. The European Commission is preparing for a Missions based science and innovation strategy in which it will be important to consider how the goal of meaningful cross-disciplinarity can be achieved. This report aims to raise the question of cross-disciplinarity again, and to suggest specific actions to further the understanding, achievement and evaluation of cross-disciplinarity in the biosciences.JRC.F.3-Chemicals Safety and Alternative Method

Accelerating progress in the Replacement, Reduction and Refinement of animal testing through better knowledge sharing

In the context of the European Commission's Communication published in response to the European Citizens' Initiative "Stop Vivisection", Action 1 aimed to conduct an assessment of current technologies, information sources and networks from all relevant sectors with potential impact on the advancement of the refinement, reduction and replacement of animals used for scientific purposes (the "Three Rs"). The main objective of this study is to map knowledge sources relevant to the Three Rs, to examine how knowledge is being shared, and to identify possible gaps and opportunities to enhance knowledge sharing. An inventory of knowledge sources (KS) potentially relevant to the Three Rs used in the area of life sciences has been compiled which should be viewed as a snapshot of the current status of knowledge sources available (the supply), and as a starting point for further analysis of knowledge sharing strategies. A public survey was also conducted to complement this study (supply versus demand), and to inform on how to proceed effectively with any knowledge management strategy. The survey has revealed that many involved in this area consider that whilst access to relevant knowledge sources is adequate, there is a need for better coordination of the sources, as well as for the communication of information. Opportunities for face-to-face exchanges are highly valued and there is a firm call for more developments in education and training at professional, university and secondary school levels.JRC.F.3-Chemicals Safety and Alternative Method

Beyond chemicals: opportunities and challenges of integrating non-chemical stressors in adverse outcome pathways

The adverse outcome pathways (AOPs) were developed to accelerate evidence-based chemical risk assessment by leveraging data from new approach methodologies. Thanks to their stressor-agnostic approach, AOPs were seen as instrumental in other fields. Here, we present AOPs that report non-chemical stressors along with the challenges encountered for their development. Challenges regarding AOPs linked to nanomaterials include non-specific molecular initiating events, limited understanding of nanomaterial biodistribution, and needs for adaptations of the in silico modeling and testing systems. Development of AOPs for radiation face challenges in how to incorporate ionizing events type, dose rate, energy deposition, and how to account for targeting multiple macromolecules. AOPs for COVID-19 required the inclusion of SARS-CoV-2-specific replicative steps to capture the essential events driving the disease. Developing AOPs to evaluate efficacy and toxicity of cell therapies necessitates addressing the cellular nature and the therapeutic function of the stressor. Finally, addressing toxicity of emerging biological stressors like microbial pesticides can learn from COVID-19 AOPs. We further discuss that the adaptations needed to expand AOP applicability beyond chemicals are mainly at the molecular and cellular levels while downstream key events at tissue or organ level, such as inflammation, are shared by many AOPs initiated by various stressors. In conclusion, although it is challenging to integrate non-chemical stressors within AOPs, this expands opportunities to account for real-world scenarios, to identify vulnerable individuals, and to bridge knowledge on mechanisms of adversity.info:eu-repo/semantics/publishedVersio

Why Adverse Outcome Pathways Need to be FAIR

Adverse outcome pathways (AOPs) provide evidence for demonstrating and assessing causality between measurable toxicological mechanisms and human or environmental adverse effects. AOPs have gained increasing attention over the past decade and are believed to provide the necessary steppingstone for more effective risk assessment of chemicals and materials and moving beyond the need for animal testing. However, as with all types of data and knowledge today, AOPs need to be reusable by machines, i.e., machine-actionable, in order to reach their full impact potential. Machine-actionability is supported by the FAIR principles, which guide findability, accessibility, interoperability, and reusability of data and knowledge. Here, we describe why AOPs need to be FAIR and touch on aspects such as the improved visibility and the increased trust that FAIRification of AOPs provides.</p

Knowledge Management for Policy: Stocktaking of one year of JRC activities

Improving knowledge management and collaborative working is a priority for overcoming silos mentalities and connecting synergies between portfolios, as envisaged in the Commission Communication C(2016)6626. In its 2030 Strategy, the JRC took up this challenge by 1) introducing a horizontal ‘knowledge management’ layer in the organigram, to mobilise scientific competences from different Directorates around the Commission’s policy goals 2) championing the implementation of new collaboration practices and platforms as well as the development of a knowledge management professionalisation programme; 3) starting to transform itself from a traditional research-producing organisation into a world-leading manager of knowledge for EU policy-making. One year after the reorganisation carried out on the 1st of July 2016 to align the JRC organigram with the new strategy, this report reviews the progress made and describes the main achievements.JRC.H-Knowledge Management (Ispra

The European Chemicals Bureau: an Overview of 15 Years Experience in EU Chemicals Legislation

From its creation in 1993, the European Chemicals Bureau (ECB) has played a vital role in the conception, development, implementation and monitoring of European Union (EU) legislation on chemicals and in contributing to the European Commission¿s participation in international chemicals programmes. The ECB has housed much of the European Commission¿s experience, capacity and historical memory in chemical risk assessment and safe chemical management. The contribution of ECB to the drafting, development and implementation of the REACH regulation has been an important one. The provision of scientific/technical expertise to the start-up phase of the newly born European Chemicals Agency (ECHA) has been essential for a swift and effective implementation of REACH. The ECB has contributed to that effort not only by selecting, recruiting and training ECHA staff but also by seconding part of its own key staff to the agency. And finally, during 2008 the ECB is completing the hand-over files and transmitting them to the ECHA, which is taking over responsibility for the operational implementation of EU legislation on chemicals.JRC.I-Institute for Health and Consumer Protection (Ispra

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2013-April 2014)

The EURL ECVAM status report provides an update on the progress made in the development, validation and regulatory acceptance of alternative methods and approaches since the last report published in April 2013. It is informing on ongoing research and development activities, validation studies, peer reviews, recommendations, strategies and international acceptance of alternative methods and approaches. R&D activities are ongoing for the complex endpoints where the toxicological processes and the mechanistic understanding have not been sufficiently elucidated yet and for which 3Rs solutions are more difficult to find. On the other hand, good progress In the validation and regulatory acceptance is made in areas where non-animal alternative methods have been developed and validated and where the focus lies in an intelligent combination/ integration of the various non-animal approaches.JRC.I.5-Systems Toxicolog

diXa: a data infrastructure for chemical safety assessment

Motivation: The field of toxicogenomics (the application of ‘-omics' technologies to risk assessment of compound toxicities) has expanded in the last decade, partly driven by new legislation, aimed at reducing animal testing in chemical risk assessment but mainly as a result of a paradigm change in toxicology towards the use and integration of genome wide data. Many research groups worldwide have generated large amounts of such toxicogenomics data. However, there is no centralized repository for archiving and making these data and associated tools for their analysis easily available. Results: The Data Infrastructure for Chemical Safety Assessment (diXa) is a robust and sustainable infrastructure storing toxicogenomics data. A central data warehouse is connected to a portal with links to chemical information and molecular and phenotype data. diXa is publicly available through a user-friendly web interface. New data can be readily deposited into diXa using guidelines and templates available online. Analysis descriptions and tools for interrogating the data are available via the diXa portal. Availability and implementation: http://www.dixa-fp7.eu Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2015)

The EURL ECVAM status report provides an update on the progress made in the development, validation and regulatory acceptance of alternative methods and approaches and their dissemination since the last report published in June 2014. It is informing on ongoing research and development activities, validation studies, peer reviews, recommendations, strategies and regulatory/international acceptance of alternative methods and approaches and dissemination activities. R&D activities within large European or International consortia continued in toxicity areas where 3Rs solutions are more difficult to find due to the underlying complexity of the area. On the other hand, toxicity areas where promising non-animal approaches have been developed, their validation and regulatory acceptance/international adoption could be progressed. Particular emphasis was given to the best and most intelligent combination and integration of these different non-animal approaches to ultimately obtain the required information without resorting to animal testing.JRC.I.5-Systems Toxicolog

Alternative methods for regulatory toxicology – a state-of-the-art review

This state-of-the art review is based on the final report of a project carried out by the European Commission’s Joint Research Centre (JRC) for the European Chemicals Agency (ECHA). The aim of the project was to review the state of the science of non-standard methods that are available for assessing the toxicological and ecotoxicological properties of chemicals. Non-standard methods refer to alternatives to animal experiments, such as in vitro tests and computational models, as well as animal methods that are not covered by current regulatory guidelines. This report therefore reviews the current scientific status of non-standard methods for a range of human health and ecotoxicological endpoints, and provides a commentary on the mechanistic basis and regulatory applicability of these methods. For completeness, and to provide context, currently accepted (standard) methods are also summarised. In particular, the following human health endpoints are covered: a) skin irritation and corrosion; b) serious eye damage and eye irritation; c) skin sensitisation; d) acute systemic toxicity; e) repeat dose toxicity; f) genotoxicity and mutagenicity; g) carcinogenicity; h) reproductive toxicity (including effects on development and fertility); i) endocrine disruption relevant to human health; and j) toxicokinetics. In relation to ecotoxicological endpoints, the report focuses on non-standard methods for acute and chronic fish toxicity. While specific reference is made to the information needs of REACH, the Biocidal Products Regulation and the Classification, Labelling and Packaging Regulation, this review is also expected to be informative in relation to the possible use of alternative and non-standard methods in other sectors, such as cosmetics and plant protection products.JRC.I.5-Systems Toxicolog