This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals for all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis for combined exposure risk assessment and approaches to assessing (eco)toxicology is given, including existing frameworks for these risk assessments. This background was evaluated, resulting in a harmonised framework for risk assessment of combined exposure to multiple chemicals. The framework is based on the risk assessment steps (problem formulation, exposure assessment, hazard identification and characterisation, and risk characterisation including uncertainty analysis), with tiered and stepwise approaches for both whole mixture approaches and component-based approaches. Specific considerations are given to component-based approaches including the grouping of chemicals into common assessment groups, the use of dose addition as a default assumption, approaches to integrate evidence of interactions and the refinement of assessment groups. Case studies are annexed in this guidance document to explore the feasibility and spectrum of applications of the proposed methods and approaches for human and animal health and ecological risk assessment. The Scientific Committee considers that this Guidance is fit for purpose for risk assessments of combined exposure to multiple chemicals and should be applied in all relevant areas of EFSA's work. Future work and research are recommended.

The European Food Safety Authority has produced this Guidance on human and animal health aspects (Part 1) of the risk assessment of nanoscience and nanotechnology applications in the food and feed chain. It covers the application areas within EFSA's remit, e.g. novel foods, food contact materials, food/feed additives and pesticides. The Guidance takes account of the new developments that have taken place since publication of the previous Guidance in 2011. Potential future developments are suggested in the scientific literature for nanoencapsulated delivery systems and nanocomposites in applications such as novel foods, food/feed additives, biocides, pesticides and food contact materials. Therefore, the Guidance has taken account of relevant new scientific studies that provide more insights to physicochemical properties, exposure assessment and hazard characterisation of nanomaterials. It specifically elaborates on physicochemical characterisation of nanomaterials in terms of how to establish whether a material is a nanomaterial, the key parameters that should be measured, the methods and techniques that can be used for characterisation of nanomaterials and their determination in complex matrices. It also details the aspects relating to exposure assessment and hazard identification and characterisation. In particular, nanospecific considerations relating to in vivo/in vitro toxicological studies are discussed and a tiered framework for toxicological testing is outlined. It describes in vitro degradation, toxicokinetics, genotoxicity as well as general issues relating to testing of nanomaterials. Depending on the initial tier results, studies may be needed to investigate reproductive and developmental toxicity, immunotoxicity, allergenicity, neurotoxicity, effects on gut microbiome and endocrine activity. The possible use of read-across to fill data gaps as well as the potential use of integrated testing strategies and the knowledge of modes/mechanisms of action are also discussed. The Guidance proposes approaches to risk characterisation and uncertainty analysis, and provides recommendations for further research in this area.

Abstract To meet the general requirement for transparency in EFSA's work, all its scientific assessments must consider uncertainty. Assessments must say clearly and unambiguously what sources of uncertainty have been identified and what is their impact on the assessment conclusion. This applies to all EFSA's areas, all types of scientific assessment and all types of uncertainty affecting assessment. This current Opinion describes the principles and methods supporting a concise Guidance Document on Uncertainty in EFSA's Scientific Assessment, published separately. These documents do not prescribe specific methods for uncertainty analysis but rather provide a flexible framework within which different methods may be selected, according to the needs of each assessment. Assessors should systematically identify sources of uncertainty, checking each part of their assessment to minimise the risk of overlooking important uncertainties. Uncertainty may be expressed qualitatively or quantitatively. It is neither necessary nor possible to quantify separately every source of uncertainty affecting an assessment. However, assessors should express in quantitative terms the combined effect of as many as possible of identified sources of uncertainty. The guidance describes practical approaches. Uncertainty analysis should be conducted in a flexible, iterative manner, starting at a level appropriate to the assessment and refining the analysis as far as is needed or possible within the time available. The methods and results of the uncertainty analysis should be reported fully and transparently. Every EFSA Panel and Unit applied the draft Guidance to at least one assessment in their work area during a trial period of one year. Experience gained in this period resulted in improved guidance. The Scientific Committee considers that uncertainty analysis will be unconditional for EFSA Panels and staff and must be embedded into scientific assessment in all areas of EFSA's work.

The European Food Safety Authority's has established procedures for the identification of emerging risk in food and feed. The main objectives are to: (i) to carry out activities aiming at identifying, assessing and disseminating information on emerging issues and ensure coordination with relevant networks and international organisations; (ii) promote the identification of data sources and data collection and /or data generation in prioritised emerging issues; and the (iii) evaluate of the collected information and identify of emerging risks. The objective(s) of the Standing Working Group on Emerging Risks (SWG-ER) is to collaborate with EFSA on the emerging risks identification (ERI) procedure and provide strategic direction for EFSA work building on past and ongoing projects related to EFSA ERI procedure. The SWG-ER considered the ERI methodologies in place and results obtained by EFSA. It was concluded that a systematic approach to the identification of emerging issues based on experts' networks is the major strength of the procedure but at present, it is mainly focused on single issues, over short to medium time horizons, no consistent weighting or ranking is applied and clear governance of emerging risks with follow-up actions is missing. The analysis highlighted weaknesses with respect to data collection, analysis and integration. No methodology is in place to estimate the value of the procedure outputs in terms of avoided risk and there is urgent need for a communication strategy that addresses the lack of data and knowledge uncertainty and addresses risk perception issues. Recommendations were given in three areas: (i) Further develop a food system-based approach including the integration of social sciences to improve understanding of interactions and dynamics between actors and drivers and the development of horizon scanning protocols; (ii) Improve data processing pipelines to prepare big data analytics, implement a data validation system and develop data sharing agreements to explore mutual benefits; and (iii) Revise the EFSA procedure for emerging risk identification to increase transparency and improve communication.

Background: Accidental allergic reactions to food are frequent and can be severe and even fatal. Objective: We sought to analyze the culprit food products and levels of unexpected allergens in accidental reactions. Methods: A prospective cohort study was conducted in adults (n = 157) with a physician-confirmed diagnosis of food allergy. During a 1-year follow-up, 73 patients reported accidental allergic reactions and the culprit food products. Food samples received (n = 51) were analyzed for a wide range of suspected noningredient allergens, and risk was quantified. Results: A very diverse range of food products was responsible for the unexpected allergic reactions. Thirty-seven percent (19/51) of products analyzed had 1 to 4 culprit allergens identified that were not supposed to be present according to the ingredient declaration. Concentrations varied from 1 to 5000 mg of protein of the allergenic food per kilogram of food product and were greatest for peanut, milk, and sesame. Milk proteins posed the highest estimated risk for objective allergic reactions. The intake of culprit allergens by patients varied considerably. For those cases in which culprit allergens were detected, the intake of at least 1 allergen exceeded the reference dose or a culprit allergen with a yet unknown reference dose was present. Both patient neglect of precautionary allergen labeling statements and omission of using a precautionary allergen labeling statement by food manufacturers seem to contribute to accidental reactions. Conclusion: A wide range of food products are causing accidental reactions in patients with food allergy. Eight different allergens not declared on the ingredient lists were detected in the culprit food products, all of which were representative of allergens regulated in the European Union.

Uncertainty analysis is the process of identifying limitations in scientific knowledge and evaluating their implications for scientific conclusions. It is therefore relevant in all EFSA's scientific assessments and also necessary, to ensure that the assessment conclusions provide reliable information for decision-making. The form and extent of uncertainty analysis, and how the conclusions should be reported, vary widely depending on the nature and context of each assessment and the degree of uncertainty that is present. This document provides concise guidance on how to identify which options for uncertainty analysis are appropriate in each assessment, and how to apply them. It is accompanied by a separate, supporting opinion that explains the key concepts and principles behind this Guidance, and describes the methods in more detail. (c) 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

12 Following a request from the European Commission to the European Food Safety Authority (EFSA), 13 EFSA's Scientific Committee (SC) prepared a guidance for the risk assessment of substances present 14 in food intended for infants below 16 weeks of age. In its approach to develop this guidance, the 15 EFSA SC took into account, among others, (i) an exposure assessment based on infant formula as the 16 only source of nutrition; (ii) knowledge of organ development in human infants, including the 17 development of the gut, metabolic and excretory capacities, the brain and brain barriers, the immune 18 system, the endocrine and reproductive systems; (iii) the overall toxicological profile of the substance 19 identified through the standard toxicological tests, including critical effects; (iv) the relevance for the 20 human infant of the neonatal experimental animal models used. The EFSA SC notes that during the 21 period from birth up to 16 weeks, infants are expected to be exclusively fed on breast milk and/or 22 infant formula. The EFSA SC views this period as the time where health-based guidance values for the 23 general population do not apply without further considerations. High infant formula consumption per 24 body weight is derived from 95 percentile consumption. The first weeks of life is the time of the 25 highest relative consumption on a body weight basis. Therefore, when performing an exposure 26 assessment, the EFSA SC proposes to use the high consumption value of 260 mL/kg bw/day. A 27 decision tree approach is proposed that enables a risk assessment of substances present in food 28 intended for infants below 16 weeks of age. The additional information needed when testing 29 substances present in food for infants below 16 weeks of age and the approach to be taken for the 30 risk assessment are on a case-by-case basis, depending on whether the substance is added 31 intentionally to food and is systemically available. 32 © 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on 33 behalf of European Food Safety Authority. 34

EFSA requested its Scientific Committee to prepare a guidance document providing generic issues and criteria to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a beneficial health effect) or not. The guidance document provides a general framework for establishing the biological relevance of observations at various stages of the assessment. Biological relevance is considered at three main stages related to the process of dealing with evidence: Development of the assessment strategy. In this context, specification of agents, effects, subjects and conditions in relation to the assessment question(s): Collection and extraction of data; Appraisal and integration of the relevance of the agents, subjects, effects and conditions, i.e. reviewing dimensions of biological relevance for each data set. A decision tree is developed to assist in the collection, identification and appraisal of relevant data for a given specific assessment question to be answered.

Abstract Following a request from the European Commission to EFSA, the EFSA Scientific Committee (SC) prepared a guidance for the risk assessment of substances present in food intended for infants below 16 weeks of age. In its approach to develop this guidance, the EFSA SC took into account, among others, (i) an exposure assessment based on infant formula as the only source of nutrition; (ii) knowledge of organ development in human infants, including the development of the gut, metabolic and excretory capacities, the brain and brain barriers, the immune system, the endocrine and reproductive systems; (iii) the overall toxicological profile of the substance identified through the standard toxicological tests, including critical effects; (iv) the relevance for the human infant of the neonatal experimental animal models used. The EFSA SC notes that during the period from birth up to 16 weeks, infants are expected to be exclusively fed on breast milk and/or infant formula. The EFSA SC views this period as the time where health‐based guidance values for the general population do not apply without further considerations. High infant formula consumption per body weight is derived from 95th percentile consumption. The first weeks of life is the time of the highest relative consumption on a body weight basis. Therefore, when performing an exposure assessment, the EFSA SC proposes to use the high consumption value of 260 mL/kg bw per day. A decision tree approach is proposed that enables a risk assessment of substances present in food intended for infants below 16 weeks of age. The additional information needed when testing substances present in food for infants below 16 weeks of age and the approach to be taken for the risk assessment are on a case‐by‐case basis, depending on whether the substance is added intentionally to food and is systemically available.

Abstract The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow‐up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight‐of‐evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health‐based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re‐assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight‐of‐evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight‐of‐evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health‐based guidance values may be established. However, if concerns for genotoxicity remain, establishing health‐based guidance values is not considered appropriate.

EFSA requested the Scientific Committee to develop a guidance document on the use of the weight of evidence approach in scientific assessments for use in all areas under EFSA's remit. The guidance document addresses the use of weight of evidence approaches in scientific assessments using both qualitative and quantitative approaches. Several case studies covering the various areas under EFSA's remit are annexed to the guidance document to illustrate the applicability of the proposed approach. Weight of evidence assessment is defined in this guidance as a process in which evidence is integrated to determine the relative support for possible answers to a question. This document considers the weight of evidence assessment as comprising three basic steps: (1) assembling the evidence into lines of evidence of similar type, (2) weighing the evidence, (3) integrating the evidence. The present document identifies reliability, relevance and consistency as three basic considerations for weighing evidence.

10 The European Commission requested the European Food Safety Authority to provide advice on the 11 following: (1) the suitability of the Unscheduled DNA synthesis in vivo assay to follow-up positive 12 results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in 13 vivo studies, particularly in the Mammalian Erythrocyte Micronucleus test; (3) the use of data in a 14 weight of evidence approach to conclude on the genotoxic potential of substances and the consequent 15 setting of health-based guidance values. The Scientific Committee (SC) concluded that the first 16 question should be addressed in both a retrospective and a prospective way: for future assessments, 17 it is recommended no longer performing the UDS test. For re-assessments, in cases with negative 18 results, other more reliable tests such as Transgenic Rodent assay or in vivo comet assay would be 19 needed to complete the assessment. Regarding the second question, the SC concluded that it should 20 be addressed in both direct and indirect lines of evidence of bone marrow exposure: toxicity to the 21 bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative 22 outcome of a study. All other direct or indirect lines of evidence of target tissue exposure should be 23 assessed within a weight-of-evidence approach. Regarding the third question, the Scientific 24 Committee concluded that any available data that may assist in reducing the uncertainty in the 25 assessment of the genotoxic potential of a substance should be taken into consideration. If the overall 26 evaluation leaves no concerns for genotoxicity, health-based guidance values may be established. 27 However, if concerns for genotoxicity remain, establishing health-based guidance values is not 28 considered appropriate and additional information would be needed to complete the assessment. 29 30 © 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on 31 behalf of the European Food Safety Authority. 32 33

EFSA is committed to assess and communicate the risks occurring in the food and feed chain from farm to fork and to provide other forms of scientific advice. This work, carried out by EFSA since its inception, has resulted in the adoption of thousands of scientific assessments. EFSA is obliged to re-assess past assessments in specific regulatory contexts such as those on food and feed additives, active substances in plant protection products and genetically modified food and feed. In other sectors, the consideration for updating past EFSA scientific assessments is taken on an ad hoc basis mainly depending on specific requests by risk managers or on EFSA self-tasking. If safety is potentially at stake in any area within EFSA's remit, the readiness to update past scientific assessments is important to keep EFSA at the forefront of science and to promote an effective risk assessment. Although this task might be very complex and resource demanding, it is fundamental to EFSA's mission. The present EFSA Scientific Committee opinion deals with scientific motivations and criteria to contribute to the timely updating of EFSA scientific assessments. It is recognised that the decision for updating should be agreed following careful consideration of all the relevant elements by the EFSA management, in collaboration with risk managers and stakeholders. The present opinion addresses the scientific approaches through which it would be possible for EFSA to increase the speed and effectiveness of the acquisition of new data, as well as, to improve the consequent evaluations to assess the relevance and reliability of new data in the context of contributing to the better definition of whether to update past scientific assessments.

The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the NOAEL approach for deriving a Reference Point (RP). Most of the modifications made to the SC guidance of 2009 concern the section providing guidance on how to apply the BMD approach. Model averaging is recommended as the preferred method for calculating the BMD confidence interval, while acknowledging that the respective tools are still under development and may not be easily accessible to all. Therefore, selecting or rejecting models is still considered as a suboptimal alternative. The set of default models to be used for BMD analysis has been reviewed, and the Akaike information criterion (AIC) has been introduced instead of the log-likelihood to characterise the goodness of fit of different mathematical models to a dose-response data set. A flowchart has also been inserted in this update to guide the reader step-by-step when performing a BMD analysis, as well as a chapter on the distributional part of dose-response models and a template for reporting a BMD analysis in a complete and transparent manner. Finally, it is recommended to always report the BMD confidence interval rather than the value of the BMD. The lower bound (BMDL) is needed as a potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL per ratio reflecting the uncertainty in the BMD estimate. This updated guidance does not call for a general re-evaluation of previous assessments where the NOAEL approach or the BMD approach as described in the 2009 SC guidance was used, in particular when the exposure is clearly smaller (e.g. more than one order of magnitude) than the health-based guidance value. Finally, the SC firmly reiterates to reconsider test guidelines given the expected wide application of the BMD approach.

EFSA asked its Scientific Committee to review its own cross-cutting guidance for scientific assessments in order to identify gaps requiring either new or the revision of existing guidance. Through strategic discussions, the Scientific Committee identified topics to be included in its 2016-2018 work programme without ranking their priority. Three topics were identified for activity leading to the development of new guidance: individual susceptibility and uncertainty factors; interpretation of epidemiological studies; history of use. These will be further discussed and introduced into the rolling work programme as time and resources become available. Work is already underway in three areas which will lead to new or revised cross-cutting guidance: chemical mixtures; follow up on the Threshold of Toxicological Concern approach; nanotechnologies. The Scientific Committee will continue to keep priorities for cross-cutting guidance across EFSA's fields of responsibility under review. (C) 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

EFSA Supporting PublicationsVolume 13, Issue 12 1129E Event reportOpen Access EFSA Scientific Colloquium 22 – Epigenetics and Risk Assessment: Where do we stand? European Food Safety Authority, European Food Safety AuthoritySearch for more papers by this authorTina Bahadori, Tina Bahadori Environmental Protection Agency, USASearch for more papers by this authorDavid Bell, David Bell European Chemicals AgencySearch for more papers by this authorSandra Ceccatelli, Sandra Ceccatelli Karolinska Institute, SESearch for more papers by this authorRaffaella Corvi, Raffaella Corvi Joint Research Centre, European CommissionSearch for more papers by this authorChrister Hogstrand, Christer Hogstrand University College London, UKSearch for more papers by this authorSharon Munn, Sharon Munn Joint Research Centre, European CommissionSearch for more papers by this authorEric Nilsson, Eric Nilsson Washington State University, USASearch for more papers by this authorDavid Spurgeon, David Spurgeon Centre for Ecology and Hydrology, UKSearch for more papers by this authorJochen Vom Brocke, Jochen Vom Brocke European Chemicals AgencySearch for more papers by this authorDiane Wray-Cahen, Diane Wray-Cahen Foreign Agricultural Service of United States Department of Agriculture, USASearch for more papers by this authorMatt Wright, Matt Wright Newcastle University, UKSearch for more papers by this authorMarco Binaglia, Marco Binaglia European Food Safety AuthoritySearch for more papers by this authorJean-Lou Dorne, Jean-Lou Dorne European Food Safety AuthoritySearch for more papers by this authorNikolaos Georgiadis, Nikolaos Georgiadis European Food Safety AuthoritySearch for more papers by this authorAndrea Germini, Andrea Germini European Food Safety AuthoritySearch for more papers by this authorGeorge Kass, George Kass European Food Safety AuthoritySearch for more papers by this authorTobin Robinson, Tobin Robinson European Food Safety AuthoritySearch for more papers by this authorAnnamaria Rossi, Annamaria Rossi European Food Safety AuthoritySearch for more papers by this authorReinhilde Schoonjans, Reinhilde Schoonjans European Food Safety AuthoritySearch for more papers by this authorAndrea Terron, Andrea Terron European Food Safety AuthoritySearch for more papers by this authorHubert Noteborn, Hubert Noteborn Netherlands Food and Consumer Product Safety Authority, NLSearch for more papers by this author European Food Safety Authority, European Food Safety AuthoritySearch for more papers by this authorTina Bahadori, Tina Bahadori Environmental Protection Agency, USASearch for more papers by this authorDavid Bell, David Bell European Chemicals AgencySearch for more papers by this authorSandra Ceccatelli, Sandra Ceccatelli Karolinska Institute, SESearch for more papers by this authorRaffaella Corvi, Raffaella Corvi Joint Research Centre, European CommissionSearch for more papers by this authorChrister Hogstrand, Christer Hogstrand University College London, UKSearch for more papers by this authorSharon Munn, Sharon Munn Joint Research Centre, European CommissionSearch for more papers by this authorEric Nilsson, Eric Nilsson Washington State University, USASearch for more papers by this authorDavid Spurgeon, David Spurgeon Centre for Ecology and Hydrology, UKSearch for more papers by this authorJochen Vom Brocke, Jochen Vom Brocke European Chemicals AgencySearch for more papers by this authorDiane Wray-Cahen, Diane Wray-Cahen Foreign Agricultural Service of United States Department of Agriculture, USASearch for more papers by this authorMatt Wright, Matt Wright Newcastle University, UKSearch for more papers by this authorMarco Binaglia, Marco Binaglia European Food Safety AuthoritySearch for more papers by this authorJean-Lou Dorne, Jean-Lou Dorne European Food Safety AuthoritySearch for more papers by this authorNikolaos Georgiadis, Nikolaos Georgiadis European Food Safety AuthoritySearch for more papers by this authorAndrea Germini, Andrea Germini European Food Safety AuthoritySearch for more papers by this authorGeorge Kass, George Kass European Food Safety AuthoritySearch for more papers by this authorTobin Robinson, Tobin Robinson European Food Safety AuthoritySearch for more papers by this authorAnnamaria Rossi, Annamaria Rossi European Food Safety AuthoritySearch for more papers by this authorReinhilde Schoonjans, Reinhilde Schoonjans European Food Safety AuthoritySearch for more papers by this authorAndrea Terron, Andrea Terron European Food Safety AuthoritySearch for more papers by this authorHubert Noteborn, Hubert Noteborn Netherlands Food and Consumer Product Safety Authority, NLSearch for more papers by this author First published: 14 December 2016 https://doi.org/10.2903/sp.efsa.2016.EN-1129Citations: 1 Question number: EFSA-Q-2016-00555 Disclaimer: The views or positions expressed in this publication do not necessarily represent in legal terms the official position of the European Food Safety Authority (EFSA). EFSA assumes no responsibility or liability for any errors or inaccuracies that may appear. Amendment: Editorial corrections were carried out on page 1-2 (authors list), 22 (references) and 24-25 (county of origin of participants) that does not materially affect the contents or outcome of this scientific output. To avoid confusion the older version has been removed from the EFSA Journal, but is available on request, as is the version showing all the changes made. Updated: 21 December 2016; 7 April 2017 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Discussion Group 1 Edwards, S. W., Tan, Y. M., Villeneuve, D. L., Meek, M. E., & McQueen, C. A. 2016. Adverse Outcome Pathways-Organizing Toxicological Information to Improve Decision Making. Journal of Pharmacology and Experimental Therapeutics, 356: 170- 181. DOI: 10.1124/jpet.115.228239 Greally, J. M., & Jacobs, M.N. 2013. In Vitro and In Vivo Testing Methods of Epigenomic Endpoints for Evaluating Endocrine Disruptors. ALTEX-Alternatives To Animal Experimentation 30: 445- 471. DOI: 10.14573/altex.2013.4.445 Kaelin, W. G., & McKnight, S. L. 2013. Influence of Metabolism on Epigenetics and Disease. Cell, 153: 56- 69. DOI: 10.1016/j.cell.2013.03.004 Lalevee, S., & Feil, R. 2015. Long noncoding RNAs in human disease: emerging mechanisms and therapeutic strategies. Epigenomics, 7: 877- 879. DOI: 10.2217/epi.15.55 Marczylo, E.L., Jacobs, M.N., & Gant, T.W. 2016. 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Maintaining a healthy environment and conserving biodiversity are major goals of environmental protection. A challenge is that protection goals outlined in legislation are often too general and broad to be directly applicable for environmental risk assessment (ERA) performed by EFSA. Therefore, they need to be translated into specific protection goals (SPGs). This Guidance presents a framework, which accounts for biodiversity and ecosystem services, to make general protection goals operational for use in all areas of EFSA's ERAs. The approach to follow has three sequential steps: (1) the identification of relevant ecosystem services; (2) the identification of service providing units (SPUs) for these ecosystem services; and (3) the specification of options for the level/parameters of protection of the SPUs using five interrelated dimensions. This last step involves the specification of options for the ecological entity and attribute to protect and the magnitude, temporal scale and spatial scale of the biologically relevant and, in the case of regulated products, tolerable effects, the latter defined in dialogue with risk managers. In order to promote transparency and consistency when developing options for the level/parameters of protection, this guidance provides considerations to justify the selected options.

The mission and tasks of the European Food Safety Authority (EFSA) include the responsibility to set up a system for identifying emerging risks. In 2007, the EFSA Scientific Cooperation (ESCO) Working Group (WG) on Emerging Risks received a mandate by the EFSA to propose an operational strategy to achieve this task. Since then, 11 meetings have been organised.The mandate includes identification of priority indicators, identification of key sources of information and best practices for data collection and exchange, and development of procedures to collect, analyze and evaluate information.The WG, building on the operational definition of "emerging risks" adopted by the EFSA in 2007, has developed an overall procedure for the collection, analysis and evaluation of the relevant data and information. The harvesting of data and information relevant to the identification of emerging risks relies principally on their detection through the use of indicators and signals. These should be considered as primary markers when screening appropriate sources electronically by means of a real-time central data collection facility. Eleven priority indicators have been identified in the areas of chemical, microbiological and nutritional hazards, with relevant examples of signals and key sources of data and information. In order to select the cases that deserve further assessment, either because there is clear indication of an emerging risk or because available data are suggestive of such a possibility, a filtering methodology of "emerging risk indicator data", based on an "intelligence" approach and making use of available IT tools, has been foreseen. Such a methodology should be developed in the follow up of the current undertaking by paying careful consideration to filtering methodologies currently used by organizations working on emerging risk identification in all sectors as well as by making use of ad hoc documents already made available to the WG by some participants.A number of different institutions/organizations currently aiming at identifying emerging risks in different sectors have been listed as potential key partners of the EFSA in such an undertaking. Although extensive information on these institutions/organizations has been gathered and reported, the work carried out so far has shown that it is quite difficult to clarify the specific methodologies used by each different body to identify emerging risks in the sector of specific competence and to report them. Information on existing procedures to identify emerging risks at national levels was collected using a survey submitted through the focal points. An inventory of selected research scientific articles and reports on emerging risks, populating an endnote database, has been initiated.Objectives and strategies for the establishment of a collaborative network between the Emerging Risks Unit and the above-mentioned key partners in a sustainable platform to exchange information have been set. Harmonization of definitions and procedures among competent organizations would allow sharing experience and optimise resources.The work carried out by the EFSA to identify emerging risks is promising. It should be continued and further intensified to complete and validate the overall methodological approach for emerging risks identification and communication, as well as by establishing a robust network between the EFSA, the European Union (EU) Member States and the other European and international partners.