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EFSA supporting publication 2014:EN-547

TECHNICAL REPORT

A systematic procedure for the identification of emerging chemical risks in the food and feed chain 1 European Food Safety Authority2, 3 European Food Safety Authority (EFSA), Parma, Italy

ABSTRACT This technical report presents a systematic framework for the identification of emerging chemical risks occurring in the food and feed chain with a likely direct or indirect impact on human, animal and/or plant health within the EFSA’s remit. Such risks may arise from intentionally and non-intentionally produced industrial chemicals, as well as certain natural contaminants that may be transferred to the food/feed chain through the environment. The proposed framework uses a variety of data sources as an input, relating to, for example, industrial chemicals, environmental occurrence of chemical contaminants, as well as software models that can be used to predict the environmental behaviour and potential toxicity of chemical substances from their structural features and physico-chemical properties. The procedure consists of a multi-step selection process that starts with a list of chemicals to which a sequence of selection criteria is applied to identify the substances of potential concern. The selection criteria take into account a number of parameters such as volumes of production or import, persistence in the environment, potential for bioaccumulation, dispersive uses, toxicity, and any available outcomes of risk assessments. The procedure has two main entry points either for industrial chemicals registered under REACH Regulation or for substances consistently detected in the environment with a subset of more specific entry points depending on specific objectives and relevant data availability. The procedure proposed in this report needs to be tested and further developed using specific examples of chemical substances, preferably through a pilot project. The results of the pilot project should inform on additional activities that might be needed for further refinement of the proposed approach. This iterative process will provide a basis for a proactive approach to understanding emerging risks from materials, products, and applications of the continually evolving scientific and technological developments.

KEY WORDS: Emerging risks, chemicals, entry points, inclusion/exclusion criteria, data sources, software models. © European Food Safety Authority, 2014

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On request from EFSA, Question No EFSA-Q-2013-00913, approved on 18 Dec 2013. Correspondence: [email protected] 3 Acknowledgement: EFSA wishes to thank the members of the Standing WG on Emerging Risks: CHAUDHRY Mohammad Qasim, DU JARDIN Patrick, GOTT David, GREGOIRE Jean Claude, HAVELAAR Arie, JANY Klaus-Dieter, KLETER Gijs, LUTTIK Robert, MACLEOD Matthew, MANTOVANI Alberto, NOERRUNG Birgit, PRZYREMBEL Hildegard, SCHANS Jan, SCHLATTER Josef Rudolf (chair), SILANO Vittorio, VÅGSHOLM Ivar, WRIGHT Matthew, the hearing expert FOTAKIS George from ECHA, for the preparatory work on this output, and EFSA staff: ALTIERI Andrea, DORNE Jean-Lou, ROBINSON Tobin, JACOBS Miriam for the support provided to this output. Suggested citation: European Food Safety Authority, 2014; A systematic procedure for the identification of emerging chemical risks in the food and feed chain. EFSA supporting publication 2014:EN-547. 40 pp. 2

Available online: www.efsa.europa.eu/publications

© European Food Safety Authority, 2014

A procedure for the identification of emerging chemical risks

SUMMARY This technical report derives from a self-task mandate of EFSA and describes a framework applicable, in principle, for the identification of emerging chemical risks, as defined by Regulation (EC) No 178/2002, occurring in the food and feed chain with a likely direct or indirect impact on humans, animals, plants or any other organisms under EFSA’s competence, mainly associated with intentionally and non-intentionally manufactured industrial chemicals as well as with natural contaminants transferred to the food/feed chain through the environment. However, in view of the need for undergoing a validation step before undertaking a wider application of the proposed methodology, the present proposal is focused on available data sources/bases and criteria more relevant for the identification of emerging risks for humans. The proposed procedure uses in a structured manner: (i) a variety of data sources that have recently become available on industrial chemicals produced in the EU, or on environmental occurrence of chemical contaminants; and (ii) software models for the prediction of the environmental behaviour, biological and toxic activity of specific chemicals from molecular structures and physico-chemical properties. In general, the framework consists of a multi-step selection procedure that starts from a list of chemical substances (referred to as “entry point”) to which a sequence of selection (inclusion/exclusion) criteria is applied to identify the chemicals of potential concern in the present context. The selection criteria take into account volumes of production or import, persistence in the environment, bioaccumulation, dispersive uses, toxicity, and any available risk assessment. The procedure is discussed in terms of: (i) main entry points in the selection procedure (e.g. list of chemicals to be screened, such as industrial chemicals registered under the REACH Regulation or chemical contaminants consistently found in the environment) with a subset of more specific entry points depending on particular objectives characterizing the application of the procedure and relevant data availability; (ii) several selection (inclusion/exclusion) criteria, including production volume, dispersive use, persistence, bioaccumulation, toxicity, evidence from existing Regulations or previous risk assessments; and (iii) selection process for the chemicals: multi-step procedure with a varying number of steps in which the outcome of each step becomes the entry point for the next step, and the last leads to the identification of emerging risks. Some selection criteria are better applied through a deterministic approach (i.e. yes/no or an exclusion threshold), whereas for others a probabilistic approach (i.e. inclusion/exclusion range) can be applied. The proposed procedure may also be applied in an iterative manner in order to evaluate the impact of different threshold values adopted for specific selection criteria on the outcome of the procedure or to test different combinations of specific selection criteria. The proposed procedure includes two main entry points - industrial chemicals registered under the REACH Regulation, and the non-intentionally produced or natural chemicals detected in different environmental compartments (e.g. water, soil and biota). The first main entry point is the REACH Registered Substances Information of industrial chemicals produced or imported in the EU. The first two main procedural steps aim at selecting those chemicals which are produced in high volumes (first step) and used with dispersive modalities (second step). The third step of the procedure consists of parallel selection of: (i) high volume industrial chemicals characterised by highly dispersive use modalities, high persistence and tendency to bioaccumulate; and (ii) high volume industrial chemicals characterised by highly dispersive use modalities and high toxicity. The fourth step consists of a probabilistic combination of these two criteria and results in the selection of industrial chemicals characterised by highly dispersive use modalities, high persistence and tendency to bioaccumulation or high toxicity. The fifth procedural step is intended to exclude from the selected chemicals those that are already regulated as food contaminants, as undesirable substances in feed, or authorised or prohibited for specific uses in the food chain. The sixth procedural step, aiming at the exclusion of chemicals already assessed by EFSA and other scientific bodies, identifies chemicals classified as emerging issues (i.e. unregulated toxic chemicals likely to occur in the food chain). The seventh, and last, procedural step, consists of the selection of chemicals classified as constituting emerging risks according to the EFSA operational definition (i.e. toxic chemicals likely to occur in the food chain that have not been regulated in food/feed and have neither been evaluated by the European Commission or EFSA, nor authorised for use in food/feed). The second main entry point aims at identifying chemicals, not included in the REACH register, using several different databases, including the Norman Network. This entry point includes, for example, chemicals of natural origin (e.g. mycotoxins, phytotoxins), or substances detected in specific environmental compartments (e.g. water, soil, sediments, biota or wildlife) which may be contaminants of the food/feed chain. After the exclusion of industrial chemicals included in the REACH Registered Substances Information, the previously-described procedure from step three to step seven applies. In the two examples described, the exclusion criteria are applied in a deterministic manner, whereas some inclusion criteria (i.e. persistence/bioaccumulation and toxicity) are applied probabilistically and others (i.e. production volume and dispersive use) deterministically. Moreover, it is important to stress that the sequence of the selection criteria is intended to be flexible. Namely, to save time and resources, criteria that can be easily and quickly applied to large numbers of chemicals in the relevant context should be always used as soon as possible in the selection procedure.


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A procedure for the identification of emerging chemical risks The procedure proposed in this report needs to be tested and further developed, preferably through a pilot project. Testing this procedure starting from a specific list of chemicals will show whether the procedure works effectively, and it may also provide additional inputs for improvement and refinement. It is expected that a software program will be needed to manage efficiently the large amount of data in the different selection steps to test the procedure. Further specific suggestions are provided on how to streamline the pilot phase to refine the proposed approach, and to test it with specific examples. The results of the proposed pilot project should then be used to decide on additional activities for the further refinement of the proposed approach.


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TABLE OF CONTENTS Abstract .................................................................................................................................................... 1 Summary .................................................................................................................................................. 2 Table of contents ...................................................................................................................................... 4 Background as provided by EFSA ........................................................................................................... 5 Terms of reference as provided by EFSA ................................................................................................ 5 1. Introduction ..................................................................................................................................... 6 1.1. The EFSA’s mission and activities on the identification of emerging risks ........................... 6 1.2. Main sources of chemicals and modulating factors ................................................................ 7 1.2.1. Main sources of chemicals ................................................................................................. 7 1.2.2. Main modulating factors of chemical contaminants occurrence ........................................ 9 1.3. Known and emerging chemical substances of concern in food and feed................................ 9 1.4. Objectives of the present report ............................................................................................ 10 2. Overall procedure to identify chemical emerging issues and risks................................................ 12 2.1. Entry points ........................................................................................................................... 12 2.2. Selection (inclusion/exclusion) criteria ................................................................................. 12 2.3. Data sources for main entry points and selection criteria ..................................................... 15 2.4. Nanomaterials/Engineered Nanomaterials ............................................................................ 16 2.4.1. Nanomaterials legislation status with respect to the REACH Regulation ........................ 17 2.4.2. OECD activities on nanomaterials.................................................................................... 17 2.5. In silico (computational) methods for predicting environmental fate and (eco)toxicity ....... 18 2.6. Physiologically-based (PB) models ...................................................................................... 19 3. Application of the procedure: (I) Intentionally produced industrial chemicals; and (II) Nonintentionally produced chemicals and substances of natural origin ....................................................... 21 3.1. (I) Emerging risks associated with intentionally produced industrial chemicals .................. 21 3.1.1. 1st entry point. The REACH list of industrial chemicals .................................................. 21 3.1.2. 1st screening step. Industrial chemicals with high volume ............................................... 22 3.1.3. 2nd screening step. Industrial chemicals with high volume and high dispersive use ........ 23 3.1.4. 3rd screening step .............................................................................................................. 24 A. Industrial chemicals with high dispersive use, and persistent and bioaccumulative nature ..... 24 B. Industrial chemicals with high volume, high dispersive use, and high toxicity........................ 25 3.1.5. 4th screening step. Toxic industrial chemicals with high volume, high dispersive use, high persistence and bioaccumulation (Combination of selection criteria 3.1.4.A. and 3.1.4.B).. 26 3.1.6. 5th screening step. Excluding regulated toxic chemicals .................................................. 26 3.1.7. 6th screening step. Excluding chemical substances evaluated by the EU ......................... 27 3.1.8. 7th screening step. Selecting substances identified as emerging issues and occurring in the food/feed chain (i.e. emerging risks) ....................................................................................... 27 3.1.9. Subsets of the 1st main entry point list. Specific lists of industrial chemicals with highly dispersive uses and some evidence of environmental persistence ................................................. 28 3.1.10. Identification of substances of very high concern within the REACH framework: differences with the approach proposed in the present paper for the identification of emerging risks in the food/feed chain ............................................................................................................ 29 3.2. (II) Emerging risks associated with non-intentionally produced chemicals and chemicals of natural origin ...................................................................................................................................... 30 3.2.1. 2nd entry point. List of chemical substances reported to occur in the environment .......... 31 3.2.2. 1st screening step. Selecting chemicals repeatedly detected in the environment .............. 32 3.2.3. 2nd screening step. Excluding the industrial chemicals registered under REACH ........... 32 3.2.4. Subsequent five screening steps ....................................................................................... 32 3.3. Considerations on the sequential implementations of exclusion/inclusion criteria .............. 32 4. Testing and further improving the proposed procedure through a pilot project ............................ 33 4.1. Application of the procedure to selected chemicals recognized as food/feed contaminants 33 4.2. Selected chemical substances registered under the REACH Regulation .............................. 33 Conclusions and recommendations ........................................................................................................ 35 References .............................................................................................................................................. 36 Appendices ............................................................................................................................................. 39 Abbreviations ......................................................................................................................................... 40 EFSA supporting publication 2014:EN-547

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BACKGROUND AS PROVIDED BY EFSA According to the EFSA’s Founding Regulation4, the Authority is required to “undertake action to identify and characterise emerging risks” in the field of food and feed safety. Thus, EFSA has the responsibility to establish structures for the screening and analysis of information sources with a view to identifying emerging risks in the fields of food and feed safety, and animal and plant health. To achieve this objective, EFSA has carried out, over recent years, extensive expert consultations and a testing phase to develop a transparent and practicable framework approach to emerging risks identification. Following the adoption of an operational definition of “emerging risk” by EFSA in 2007, ad hoc Working Groups along with a Network of Member States, have been convened to start discussing and testing data collection and evaluation approaches in such a framework. In 2011, the Working Group on Methodology for emerging risks identification established to support EFSA in the further development of a transparent framework assessed the performance of the EFSA procedure in place and provided recommendations for improvement. The Working Group proposed a revised simplified framework including three main steps: 1) identification of emerging issues5, 2) identification of appropriate data sources and data collection, 3) final evaluation and identification of emerging risks. Emerging issues should be identified at the beginning of the process preferably through expert consultations and access to specialised data bases. The Working Group on Methodology recognised that the identification of emerging risks requires a high level of expertise, as it is typically based on scattered information and major data gaps, which are difficult to interpret without a solid knowledge of the entire food chain. One of the major constraints identified in the efficiency of the procedure piloted by EFSA was the direct accessibility to experts from the Scientific Committee and Panels. This was deemed to be crucial for an efficient identification of specific issues for focussed monitoring and a meaningful expert evaluation of the issues identified. In 2013, EFSA established a Standing Working Group of the Scientific Committee on Emerging Risks, to provide scientific support to EFSA throughout the entire process: from the identification of emerging issues that merit further consideration to the final identification of emerging risks. Furthermore, experience in operating the pilot phase of the process at EFSA has shown a need to improve the decision and priority making process for attributing resources to follow up on identified emerging risks. To this end, the Working Group of the Scientific Committee on Emerging Risks reports to the Scientific Committee. The Scientific Committee will then be responsible for providing recommendations to conclude on the follow up actions.

TERMS OF REFERENCE AS PROVIDED BY EFSA The main objective of the Standing Working Group on Emerging Risks is to collaborate with EFSA on the emerging risks identification process, i.e. from the identification of priority emerging issues that merit further consideration to the final identification of emerging risks. This report deals with a systematic procedure for the identification of emerging chemical risks in the food and feed chain.

4 Regulation (EC) No 178/2002 of the European Parliament and of the Council of 28 January 2002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety. OJ L 31, 1.2.2002, p. 1-24. 5 “Emerging issues” are identified at the beginning of the Emerging Risk Identification process as issues that may merit further investigation and additional data collection. Emerging issues can include specific issues (e.g. specific chemical substance or a pathogen), as well as general issues such as drivers of change (e.g. climate change). Risk management issues resulting from a lack of compliance with existing Regulations should be excluded.


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1.

INTRODUCTION

1.1.

The EFSA’s mission and activities on the identification of emerging risks

According to Art. 34 of Regulation (EC) 178/2002, EFSA shall establish “monitoring procedures for systematically searching for, collecting, collating and analysing information and data with a view to the identification of emerging risks in the fields within its mission” (i.e. human, animal and plant health in relation to the food and feed chain). “Where EFSA has information leading to suspect an emerging serious risk, it shall request additional information from the Member States, other Community Agencies and the Commission. The Member States, the Community Agencies concerned and the Commission shall reply as a matter of urgency and forward any relevant information at their disposal. The Authority shall use all the information it receives in the performance of its mission to identify an emerging risk. The Authority shall forward the evaluation and information collected on emerging risks to the European Parliament, the Commission and the Member States.” For the correct understanding and implementation of the above legislation, it is very important to stress that it requires a two-step procedure. The first step is based on the suspicion of emerging serious risks and request of additional information by EFSA to the Member States, other Community Agencies and the Commission that would make it possible to move from a simple suspicion to a more scientifically-based conclusion about the identification of the emerging risk. The second step is based on the identification of emerging risks, i.e. scientifically-based possibility/likelihood of harmful effects to human/animal/plant health associated with the exposure to specific hazards, although there may remain a need for additional scientific information to carry out a full risk assessment. As mentioned in the Founding Regulation, the Authority shall forward the evaluation and information collected on the emerging risks identified to the European Parliament, the Commission and the Member States. This prescription has two main objectives: (i) the first one being the adoption of specific measures justified according to the precautionary principle (see Art. 7 of Reg. (EC) 178/2002); and (ii) the second, and more common, one being the adoption of decisions to gather and/or to produce the additional missing data to enable a full risk assessment. Therefore, it is very important that information on each emerging risk identified is provided by EFSA to the Stakeholders with a clear indication of additional data needed for the full risk assessment. To this end, information on emerging risks should be shared with the relevant EFSA Panels, to check for additional data requirements, before reporting to the European Parliament, Commission and Member States. These considerations highlight that a formal declaration of an emerging risk by EFSA would imply a careful consideration by the European Commission and Member States responsible for deciding on research financing. EFSA has worked intensively to develop a methodological approach to identify emerging risks since its inception in 2003 (Robinson et al., 2012). According to EFSA’s operational definition of emerging risk adopted in 2007, an emerging risk is understood to be associated with the probability of a harm (i.e. injury or damage or adverse response) to human, animal and/or plant health, resulting from a newly identified hazard which may be an agent of physical, chemical or biological nature to which a significant exposure of the target organism may occur, or from an unexpected new or increased significant exposure and/or susceptibility to a known hazard through the food chain for humans, through the feed chain for animals and through the environment for plants6. Therefore, the identification of an emerging risk can be stated as: •

A new hazard, to which a significant exposure of humans, animals and/or plants is possible/likely

•

A new/increased exposure of humans, animals/or plants to a known hazard as possible/likely

•

Increased sensitivity of humans, animals and/or plants to a known hazard, e.g. as a consequence of immune depression in persons exposed

A preliminary important step in such a process is identified when a new exposure of human beings, animals and/or plants is discovered to an agent of unknown (but possible) toxicity/pathogenicity or a new toxicity/pathogenicity is discovered for a hazard with unknown (but possible) human, animal and/or plant exposure. Such a condition is operationally defined in the present context as an “emerging issue” that 6 Food as defined in this report is any substance or product, whether processed, partially processed or unprocessed, intended to be, or reasonably expected to be ingested by humans with the exemptions mentioned in art.2 of Regulation (EC) 178/2002 and covers all types of foods including food supplements and fortified foods. ‘Feed’ (or ‘feeding stuff’) means any substance or product, including additives, whether processed, partially processed or unprocessed, intended to be used for oral feeding to Animals (art.3(4) , Reg (EC) 178/2002).


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conceptually corresponds to the suspicion of serious emerging risk mentioned in the second paragraph of Art. 34 of Regulation (EC) 178/2002. In fact, it clearly points to the need for getting more toxicity/pathogenicity or exposure data, respectively, which could lead to the identification an emerging risk. Emerging risks or issues can be identified in association with a variety of biological, chemical and/or physical hazards of natural or industrial origin, as well as for a variety of target organisms, including human beings, animals and/or plants. In view of EFSA status as European Authority for Food Safety, the mandate provided by Regulation (EC) 178/2002 in terms of emerging risks identification applies to the EU and to its food and feed chain. The present procedure, however, could also be applied to identify chemical emerging issues in food or feed imported from Third Countries, but, in such a case, the data sources (i.e. Reach Regulation7 and the REACH Registered Substances Information8 of industrial chemicals produced or imported in the EU) to be used should be those relevant for those Third Countries and not those mentioned in this report which pertain exclusively with chemical substances produced or imported in the EU.

1.2.

Main sources of chemicals and modulating factors

The following subsections describe the main sources of chemicals likely to be associated with emerging risks to human/animal/plant health under specific conditions, and factors modulating the unintentional occurrence of these chemicals in the food/feed chain.

1.2.1.

Main sources of chemicals

Intentionally made chemicals. The importance from a public health standpoint of intentionally-produced chemicals as a source of chemicals occurring in the food/feed chain is generally recognized. The chemical industry has been growing worldwide and is economically significant in the EU. In the analysis recently compiled for 168 toxic chemicals, based on production quantities collected pursuant to the Prodcom Regulation9, the toxicity classes were assigned according to the classification and labelling system (“risk phrases” or Rphrases)10. The production volumes of toxic chemicals (i.e. carcinogenic, mutagenic, reprotoxic, chronically toxic, very toxic, toxic and harmful) in the EU amounted to about 200 million tons per year during the last 7 years (EEA, 2011). The relative importance of the toxic substances belonging to the above mentioned different toxicity classes was as follows: carcinogenic, mutagenic and reprotoxic (CMR) chemicals (16 %), chronically toxic chemicals (4 %), very toxic chemicals (21 %), toxic chemical (32 %) and harmful chemicals (27 %) (EEA, 2011). Man-made chemical substances can be released during any stage of their lifecycle (Figure 1) from production (or import) through processing, manufacturing and use (industrial and consumer) to disposal. This can lead to gross pollution (poorly managed industries, contaminated sites, and accidents), as well as diffuse releases that may lead to long term exposure to low levels of chemicals and/or chemical mixtures. For substances used in slowly degradable products or construction materials, emissions resulting from waste disposal stage can continue several decades after production and processing of a substance or a product. This is one reason why some substances are still found in the environment or in biological systems decades after their use has ceased.

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Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC 8 http://www.echa.europa.eu/ 9 Regulation (EC) No 1991/3924/EC on the establishment of a Community survey of industrial production. 10 Designated for the individual substances in Annex VI to the Hazardous Substances Directive as amended by the EC Directive 2001/59/EC, adapting to technical progress for the 28th time Council Directive 67/548/EC on the approximation of the laws, Regulations and administrative provisions relating to the classification, packaging and labeling of potentially hazardous substances.


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Figure 1:

Life cycle of chemical products (Source: European Environment Agency11).

Non-intentionally produced chemical substances. These figures, in addition to being partial with respect to chemicals manufactured by industry, do not include the large amounts of toxic or harmful chemical substances released into the environment, but not intentionally-produced, by industrial and other activities such as those related to mining, gas and oil exploitation, energy transformation, transport, urban activities, and waste disposal. Moreover, hazardous chemical substances are also generated during the processing of food or feed (food/feed process contaminants). Processing means: (i) changing plants or animals into what we recognize as food (e.g. harvesting, slaughtering, fractionation, fermentation and smoking); (ii) getting food from the farm or processing plant to the consumer or a food service facility like a restaurant, or hospital kitchen (e.g. distribution and storage); (iii) getting the food ready to eat (e.g. cooking). A number of examples of contamination during processing are known, although food processing employs several techniques to increase food safety. However, some of these processing measures themselves may produce chemical by-products harmful to human health. The best known processes that cause substantial changes in food include cooking (heat treatment in various ways), fermentation, acid hydrolysis, etc. Examples of process contaminants produced by cooking include acrylamide formation in fried starchy food, polyaromatic hydrocarbons (PAHs) formation in grilled meat and heterocyclic amines formation in (certain) cooked foods. Fermentation and acid hydrolysis are two commonly used methods to break down or convert food components into smaller fragments or individual molecules. During these processes, many reaction products may be formed. For example, ethyl carbamate may be generated during fermentation, and 3-chloropropane-1,2-diol (3-MCPD) during acid hydrolysis in soy sauce.

Natural occurring substances. Natural events, such as volcanic emissions and fires, or agents as well as toxin-producing microorganisms such as certain Aspergillus and Fusarium fungi, dinoflagellates, cyanobacteria as well as certain plant species contribute to the overall hazardous chemical load in the environment and/or directly in the food/feed chain. Moreover, it should also be considered that, even for naturally occurring chemicals, human activities may increase their mobility or the amount, allowing them to enter the food/feed chain at higher levels than would otherwise occur.

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1.2.2.

Main modulating factors of chemical contaminants occurrence

Hazardous substances released into the environment, especially those that do not break down easily, may enter different environmental compartments and the food or feed chain, thus posing the likelihood of exposure of human beings, animals and/or plants through different pathways. Whether a substance can be found in the air, soil, aqueous environment or in the food/feed chain, depends on a number of factors, including how the substance is released, the amount released, pattern of release and, most importantly, its physico-chemical properties. The relative importance of different sources of contamination, therefore, depends on a number of factors. For instance, the major sources of contamination of the aquatic environment are treated and untreated wastewaters, run-offs, atmospheric deposition (including spray drift), and leaching. The fate of emissions in a particular water body will depend not only on the amount of the substance emitted, but also on the transport, dispersion and transformation processes (e.g. biodegradation, hydrolysis, photolysis) in the receiving body. The preventative measures, such as (bio)degradation and sewage treatment, taken to minimize contamination are therefore important considerations. As indicated by the Codes of Practice developed by the Codex Alimentarius12, there are several factors which may affect levels of chemical intermediates/impurities, posing a potential risk to human, animal health or to the environment, including: (i) the local environmental and climatic conditions; (ii) the primary production conditions, including fertilization, harvesting and drying modalities; (iii) the storage and transport conditions including moisture levels, temperature and exposure to light; (iv) the processing and manufacturing techniques applied to specific products including the use of high temperatures, particular milling conditions or contaminated water; (v) the nature of the food/feed product including those deriving from older animals or specific animal organs such as kidneys; and (vi) the properties of the hazardous chemical substance considered, including its physico-chemical properties, especially persistence.

1.3.

Known and emerging chemical substances of concern in food and feed

The assessment and control of risks associated with hazardous chemical substances of concern, especially in the food/feed chain, has a very high priority in the public health agenda of the European institutions. Well known chemical substances of concern in the food/feed chain range from heavy metals like lead, mercury and ionic species like perchlorate, to organic substances, including dioxins and dioxin-like polychlorinated biphenyls (PCBs), brominated flame retardants (BfRs) and perfluoroalkyls (PFAs) and the so called persistent organic pollutants (POPs). Legacy POPs such as PCBs have been banned for industrial or agricultural use for many years, but have remained in the food/feed chain due to their high environmental stability and persistence. Other POPs have more recently been identified in the environment and the food/feed chain (for example, brominated flame retardants and perfluorinated compounds). Similarly, while some processing food contaminants have been known for decades (e.g. PAHs), the formation and presence of certain chemicals in foods has been discovered relatively recently (e.g., acrylamide, furan and perchlorate). A number of Regulations have been adopted at EU level to prescribe maximum levels of specific contaminants in food (e.g. Regulation (EC) 1881/2006 and subsequent modifications and integrations) as well as of undesirable substances in feed (see Directive 2002/32/EC and subsequent modifications and integrations). Moreover, detailed monitoring obligations have been adopted as applicable to specific chemical contaminants in food and feed. In particular, the Council Directives 96/22/EC and 96/23/EC on measures to monitor certain substances and residues thereof in live animals and animal products requires Member States to adopt and implement a national residue monitoring plan for specific groups of chemicals. That Directive lays down specific sampling levels and frequencies, as well as the groups of substances to be monitored for each food commodity (for example see Commission Decision 97/747/EC for milk, eggs, honey, rabbits and game products, Commission Regulation (EU) No 37/2010 for veterinary medicinal products). In their national plans Member States target the groups of animals/gender/age combinations where the probability of finding residues is the highest. This approach is different from random sampling, where the objective is to gather data for instance to evaluate consumer exposure to a specific substance. Many contaminants have been assessed by the EC Scientific Committees on food and feed before 2003 and by EFSA since 2003. In this context, it is also remarkable that in the framework of Articles 23 and 33 of Regulation (EC) No 178/2002, EFSA has received a mandate to collect on a continuous basis all available data on the occurrence of chemical contaminants in food and feed. In particular, in mandate M-2010-0374 of the EC to EFSA on the “Request for continued data collection and analysis for nitrates, mycotoxins, dioxins and PCBs in 12

Available from the “Official Standards” section website at: http://www.codexalimentarius.net/web/index_en.jsp


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food and undesirable substances in feed” the Commission summarises the scope of the continuous data collection by referring to previous mandates and indicating additional substances: “The permanent data collection exercise could in principle encompass the whole field of contaminants in feed and food. However, to focus the work, it is appropriate also for the competent authorities and stakeholder organisations which have to provide data, to identify specific topics for which a permanent occurrence data collection exercise is to be set up. Several requests for data collections were already addressed by the Commission to EFSA, e.g. on heavy metals, furan, acrylamide in food, etc.” On this basis, after consulting with the Commission and the ad hoc Member State Network (Data Collection and Monitoring Expert Group on Chemical Occurrence), a continuous call for data has been issued by EFSA on a list of chemical contaminants13. However, the undiscovered or unrecognised occurrence of a considerable number of additional substances which may pose a hazard to human/animal/plant health in the food/feed chain is currently considered to be likely. In fact, the total number of man-made and natural substances of concern already assessed, regulated or monitored, is small when compared to the estimates of about 100 000 industrial chemicals in regular use, of which several thousand account for about 90 % of the total mass used (Holt, 2000). Moreover, several hundreds of new chemical substances are being manufactured each year as a consequence of the on-going fast innovation in the chemical industry and the food/feed technology and several other trends leading to new processes. According to the European Environment Agency (EEA, 2011), there are potential risks possibly deriving from some emerging contaminants, both in terms of their concentrations and their effects in the aquatic environment and in the food/feed chain. Emerging contaminants are not included in routine monitoring programs. Unless a substance is regulated or the need for an ad hoc monitoring has been identified, widespread monitoring is unlikely. However, without such monitoring data, the risks cannot be assessed. Therefore, it is not surprising that the awareness of potential effects of a range of emerging contaminants remains largely fragmentary and that a more pro-active cost-effective approach, through the exploitation of all the available data sources, even if developed for different objectives, is needed to identify in a more comprehensive and timely manner the substances that may pose significant risks to human and/or animal and/or plant health.

1.4.

Objectives of the present report

This report describes a prototype framework for systematically identifying emerging issues and risks (as previously defined in Section 1) associated with chemical substances intentionally or non-intentionally produced, or of natural origin, transferred to the food/feed chain through the environment. This procedure is not intended for the identification of emerging risks associated with process contaminants which are formed during food/feed cooking or other forms of preparation. In fact, considering that food processing contaminants are not intentionally produced and do not generally occur at high levels in the environment, the objective of identifying emerging risks from food processing is best addressed by ad hoc research programs, such as the DG-Research and Innovation PROMETHEUS project (2011-2014)14. PROMETHEUS uses a novel holistic analytical approach of continuous real-time monitoring of contaminant formation during food processing. Ambient mass spectrometry, fluorescence spectroscopy and image analysis measure the relevant contaminants, their precursors and some quality indicators simultaneously. However, once new process contaminants have been identified and their toxicity has to be investigated, some data sources described in the present paper may prove to be helpful also in these cases. The approach described herein provides a practicable way forward based on a structured and integrated use of data and information already gathered for a variety of different purposes, and may be applied to a large number of substances with relatively limited resources. It takes into account the regulatory, scientific and technical developments that have been taking place in the EU and worldwide in recent years. These include new sources of information on chemical, with toxicological and occurrence data on a large number of substances produced in the EU and software models for the prediction of the environmental behaviour and biological/toxicological activity of specific substances from their molecular structures and physico-chemical properties. The approach proposed intends to be: • • 13 14

systematic as indicated by Regulation EC 178/2002 (see first paragraph in Art.34) pro-active in the sense of taking into account specific groups of chemicals (e.g. industrial chemicals), and useful in identifying not only chemical substances likely to represent an emerging risk in the

http://www.efsa.europa.eu/it/data/call/datex101217.htm http://processing-contaminants-prometheus.com/ProjectOverview.php


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• •

food/feed chain, but also those unlikely to be emerging risks due to their properties or other valid considerations applicable, with relatively limited resources, to a large number of chemicals not assessed so far by using data and information already available or searched on an ad hoc basis following a priority identification; and flexible enough to be applied at the EU, Member State, or regional level to different groups of chemicals (e.g. man-made or natural contaminants) and different targets such as human being, animals or plants

Moreover, practicable approaches for testing and improving the proposed procedure are also addressed.


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2.

OVERALL PROCEDURE TO IDENTIFY CHEMICAL EMERGING ISSUES AND RISKS

The proposed procedure to identify chemical emerging issues and risks consists of a multi-step selection approach that starts with an initial list of chemicals (main entry point) to which a sequence of selection (inclusion/exclusion) criteria is applied. In view of the EFSA broad mission, two entry points have been chosen as examples to implement the developed framework, i.e. the list of industrial chemicals registered under the REACH legislation is likely to include a variety of new chemicals or chemicals with new toxicity data, and the list elaborated by the Norman Network15, amended when necessary with data from recent relevant publications, likely to include a variety of known toxic chemicals for which a significant exposure may occur. These two entry points are obviously not intended to be exhaustive. For instance, to identify emerging risks in areas impacted by specific industrial activities/processes, ad hoc entry lists based on specialised literature concerning the nature of contaminants likely to be released/produced by the specific industry could be developed. Therefore, the choice of entry points other that those discussed in the present report could be fully justified depending on the overall objectives pursued and on the practical context under which the selection takes place. Several selection criteria have been identified. Some selection criteria are better applied through a deterministic approach (i.e. yes/no or an exclusion threshold), whereas to others a probabilistic approach (e.g. inclusion/exclusion subjective to a probability range) can be preferably applied. The procedure can be iterated to screen chemicals eliminated in previous runs of the procedure. The availability of data sources and the nature of the data provided are of pivotal importance in order to develop an entry list and apply the selection criteria. The different components of the proposed procedure (i.e. entry points, selection criteria and relevant data sources) are described in the following sections.

2.1.

Entry points

Two examples of groups of substances and related entry points are discussed in this report to illustrate the approach: •

industrial chemicals as a 1st entry point: list of industrial chemicals derived from the REACH Registered Substances Information

•

contaminants repeatedly detected in the environment as a 2nd entry point: list of substances derived from the Norman Network16 and from other lists of chemicals mainly used for confirmatory purposes

The first main entry point (the list of industrial chemicals) is to globally address the group of chemicals registered under the REACH Regulation (i.e. all the industrial chemicals produced or imported in amounts exceeding 1 ton per year). The REACH registration procedure imposes on the manufacturer/importer also special obligations to provide specific data on the chemicals registered. The second main entry point includes a list of chemicals derived from monitoring programs undertaken to detect chemical contaminants occurring/accumulating in the environment. In developing the list of chemicals, a priority could be given to those consistently detected in one or more specific compartments of the environment. These substances include persistent and bio-accumulative industrial chemicals released in the environment in large amounts which, except for the case of industrial contaminants surviving from discontinued manufacturing/importation processes, are already included in the previous main entry point, and natural contaminants which are not.

2.2.

Selection (inclusion/exclusion) criteria

This section deals with inclusion/exclusion criteria to identify, among industrial and environmental substances, those of potential concern for the food/feed chain (see Table 1 for the full list of selection criteria). Other selection criteria may be identified depending on the nature of the initial list of substances to be screened.

15

http://www.norman-network.net/index_php.php. for more information on the Norman Network see Appendix A. List of NORMAN emerging substances (most frequently discussed) - (latest update approved March 2011), available at http://www.norman-network.net/index_php.php?module=public/about_us/emerging&menu2=public/about_us/about_us 16


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The main inclusion criteria characterise the likelihood for a specific chemical: (i) to reach humans or animals through the food/feed chain or plants through the environment; and (ii) to be highly toxic for humans, animals and/or plants. For example, the likelihood of occurrence in the food/feed chain depends, in the case of industrial chemicals, on the amounts produced, the use modalities, the environmental release, persistence and bioaccumulation, especially in aquatic and terrestrial species used as food or feed, or as food and feed ingredients. The assessment of the toxicity profiles of specific chemical substances depends on the availability of relevant in vivo, in vitro, or structure-activity based toxicity data. Main exclusion criteria depend on whether a specific chemical substance has already been regulated, e.g. as a chemical contaminant, or scientifically assessed and judged to be of low health concern. An additional exclusion criterion applies to substances already authorised for being used in the food/feed chain, such as additives or solvents, as for these substances a risk assessment has already been carried out. The application of each criterion is a step of the selection procedure applied to the list of chemicals of the main entry point, thus resulting in a multistep procedure consisting of a variable number of steps depending on the entry point. Except for the step leading to the identification of the emerging risks, the outcome from any selection step is also an entry point for the subsequent step.

Table 1:

Selection criteria and their data sources.

Inclusion criteria Manufactured or imported volume (tonnes/year)

Dispersive use modalities

Persistence

Bioaccumulation

Toxicity

Occurrence in the food/feed chain

Exclusion criteria Regulated contaminants in food and feed

Comment and relevant main data source Only applicable to industrial chemicals. Higher volumes imply a higher probability of presence in the environment and, as a consequence, in the food/feed chain. Data source: The REACH Registered Substances Information. Only applicable to industrial chemical substances. Dispersive uses mean any processing, formulation, consumption, storage, keeping, treatment, filling into containers, transfer from one container to another, mixing, production of an article or any other utilisation likely to result in the release of the substance into the environment and, as a possible consequence, to the food/feed chain. The classification procedure is available in the “REACH guidance on information requirements and chemical safety assessment” (Chapter R.12: Use descriptor system17). Data source: The REACH Registered Substances Information. Persistence implies a higher probability of presence in the environment and, as a possible consequence, in the food/feed chain. Data sources: (i) The REACH Registered Substances Information; (ii) the e-ChemPortal18; (iii) software models for predicting environmental fate; and (iv) data bases concerning chemicals detected in the environment. Bioaccumulation implies a higher probability of presence in specific segments of the food/feed chain. Data sources: (i) The REACH Registered Substances Information; (ii) the e-ChemPortal; (iii) software models for predicting environmental fate; and (iv) data bases concerning chemicals detected in environmental compartments. Information on the toxicity of substances for human beings, animals and/or plants is relevant in the context of emerging issues identification. Data sources: (i) The REACH Registered Substances Information; (ii) the e-ChemPortal; (iii) software models based on structure-activity relationship; and (iv) modelling tools that help to link chemical contamination with observed deterioration of ecological quality. Occurrence of a chemical in the food/feed chain is necessary for the identification of an emerging risk in the present context. Data sources: (i) the e-ChemPortal; (ii) specialised literature on occurrence of chemicals in food/feed; (iii) national surveys in EU Member States; (iv) international databases such as the GEMS Food19; (v) ad hoc EFSA call for data; or (vi) ad hoc monitoring of the food/feed chain. Comment and relevant main data source Chemical contaminants which have been prohibited or regulated in

17

http://echa.europa.eu/documents/10162/13632/information_requirements_r12_en.pdf http://www.echemportal.org/echemportal/index?pageID=0&request_locale=en 19 https://extranet.who.int/gemsfood/ 18


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Regulated substances for use in food or feed

Substances already assessed in food or feed but not regulated

terms of maximum permissible levels in food/feed are well known and have been assessed. While new and unexpected issues of concern might be identified for some regulated contaminants, overall these chemical substances have low importance in the context of emerging issues identification. Data sources: EU Regulations on contaminants. Chemical substances which are regulated for use in the food/feed chain such as pesticides, additives and solvents, are well known and have been assessed. Therefore, even though new and unexpected issues of concern might be pointed out for some regulated substances, overall these chemical substances have low priority in the context of the present framework. Data sources: EU Regulations on substances authorised for use in food/feed (e.g. food/feed additives, solvents and other products). Chemical substances which have been assessed by EFSA since 2003, or previously by the Scientific Committees of the European Commission, or by other scientific Bodies such as JEFCA are well known and, therefore, have low priority in the context of emerging risk identification, unless new and unexpected issues of concern are identified. Data sources: Risk assessment opinions provided by scientific Bodies (e.g. EFSA, Commission’s Scientific Committees, JECFA, IARC).

As previously noted, some selection criteria will be applied using a deterministic approach (i.e. yes/no or an exclusion threshold), whereas to others a probabilistic approach (i.e. inclusion/exclusion range) can be applied. For instance, all the above mentioned exclusion criteria are deterministic. In fact, if a chemical substance has already been identified and submitted for risk assessment, it is of low interest in the present context and should generally be excluded. In the case of the above mentioned inclusion criteria, the manufacturing/import volume is a quantitative parameter that can be used as a deterministic criterion (e.g. by excluding all chemicals below a threshold of 1 ton/year) and is very helpful to establish a simple priority sequence as it is impossible to deal with thousands of chemicals at the same time. Starting from higher production volume chemicals increases the likelihood of detecting the selected substances in the environment and in the food/feed chain if present. The criterion “dispersive use” is a qualitative one that would be very difficult to deal with in probabilistic terms and it is easier to rely on the REACH “environmental release category” as yes/no inclusion criterion. For the criteria based on toxicity, moving to quantitative probabilistic considerations could be difficult in view of the likely limitations of quantitative toxicity data, and it would be more practical to concentrate on substances for which there are sound specific indications of toxicity (i.e. carcinogenic, mutagenic, reprotoxic and/or chronically toxic for mammals and/or toxicity for fish and/or for birds or plants). On the other hand, depending on the specific context of the emerging risk identification process, it could be reasonable to focus on selected endpoints only and disregard toxic endpoints considered of minor relevance in a specific context. In any case, it would be important to clarify the underlying reasoning for deciding on the use of the applied criteria. The criteria which are more likely to be amenable to a probabilistic approach are persistence and bioaccumulation potential. For substances for which a (very) high toxicity has been shown, it would be reasonable to include even moderate levels of persistence/bioaccumulation which might otherwise be excluded. A probabilistic approach could also be justified in the combination of toxicity and persistence/bioaccumulation as a function of the context in which the selection takes place. For instance, if the selection aims at clarifying the possible impact of a pollution source (e.g. an industrial plant) on the immediately surrounding environment, it could be reasonable to attribute more weight to the toxicity of the chemicals released into the environment than to their persistence or bioaccumulability. In some cases, the “entry point” database may also be used as selection criteria. For example, the presence of a chemical in the list of chemicals detected in water, soil, sediment or biota is a clear “entry point” for the procedure under consideration. If the chemical in question is known to be an industrial chemical characterised by high manufacturing volume, dispersive use and environmental persistence and bioaccumulation, the occurrence in one or more environmental compartments could also be simply seen as a confirmation of the other data. On the other hand, if the chemical in question is a natural occurring substance, the presence in one or more environmental compartments is an important information not otherwise available. The sequence of use of specific criteria in the selection procedure may change depending on the substance considered. For instance, the occurrence of an industrial chemical in food/feed is an essential element at the end EFSA supporting publication 2014:EN-547

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of the procedure to conclude that an emerging risk has been identified. On the other hand, in the case of a process contaminant, its detection in food/feed may generally represent the start of the procedure. In any case, the chemicals identified through the proposed approach should be considered to belong to the group representing emerging issues or emerging risks, respectively, only when the evidence exists for specific substances to match all the criteria used for the previous definition of an emerging issue or risk in section 1.

2.3.

Data sources for main entry points and selection criteria

For the application of the procedure, the availability of data sources is essential. Table 2 includes a list of main data sources and several databases on chemical substances providing different types of information. The data sources addressed in this report are not necessarily exhaustive. However, they provide information that should enable the proposed procedure to be tested. All the mentioned databases are at least partially accessible and full accessibility will need to be verified and may require collaboration between EFSA and bodies responsible for the establishment and/or maintenance of the databases. This is the case, for instance, for the REACH Registered Substances Information which includes public information as well as confidential and ad hoc data that are only accessible to the European Chemicals Agency (ECHA) or to national competent Authorities in Member States. Some restrictions, although of different nature, may also exist for accessing the Norman Network database. Even for fully accessible databases, it is important to clarify specific issues such as the quality of data and to carry out some practical exercises in order to make an optimal use of the available data. It is important to have these issues clearly in mind when undertaking a pilot project to test the procedure.

Table 2:

Main data sources for the application of the procedure aiming at identifying emerging issues and

risks20. Data source REACH Registered Substances Information

e-ChemPortal

Norman Network

DG-Joint Research Centre monitoring programme

U.S. Geological Survey (USGS) Toxic Substances Hydrology (Toxics) Program and The Northern (Canadian) 20

Description Data made available by the REACH include information on thousands of registered industrial chemicals on manufacture and use, physico-chemical, toxicological and ecotoxicological properties. Most of these data are expected to become available at different time-points, depending on the amounts/volumes of substance manufactured/imported (according to the timelines as requested by the REACH Regulation). The e-ChemPortal provides free public access to information on properties of chemicals: (i) Physico-chemical properties; (ii) Environmental fate and behaviour; (iii) Ecotoxicity and (iv) Toxicity. The e-ChemPortal allows simultaneous searching of reports and datasets by chemical name and by chemical property. Direct links to collections of chemical hazard and risk information prepared for governmental chemical review programs at national, regional and international levels are provided. Classification results according to national/regional hazard classification schemes or to the Globally Harmonised System of classification and labelling of Chemicals are also provided when available. The eChemPortal provides information also on exposure and use of chemicals. This Network deals with more recent information on emerging substances, with an overview of benchmark values on the occurrence of emerging substances across Europe, traces the occurrence of substances which are currently not included in major monitoring schemes because of a lack of knowledge of their identity; and defines new emerging threats in various environmental compartments. The JRC has recently organised a large scale sampling and monitoring program at 122 river stations and 164 groundwater sites in 27 European countries in order to obtain a panEuropean perspective on the occurrence and levels of a range of organic substances, including many of those considered to be emerging pollutants (Loos et al., 2009 and 2010). Emerging pollutants are those for whom the potential for adverse effects has only recently become apparent (in contrast, for example, to metals and organo-chlorines) and for which the understanding of sources, emissions, levels and effects in the aquatic environment remains limited. Across the JRC study, nearly 60 organic substances were investigated. These include pesticides, pharmaceuticals, hormones, antibiotics, perfluorinated surfactants and other industrial chemicals. These two databases are examples of initiatives aiming at conducting large-scale reconnaissance of new contaminants in Third Countries. Their value in a European context could be considered for confirmatory purposes in the advanced phase of the process addressed herein.

For more detailed information see the Appendix A.


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A procedure for the identification of emerging chemical risks Contaminants Program (NCP) GEMS/Food Program

EFSA databases

Databases of organizations competent for risk assessment in the food/feed sector other than EFSA EUR-Lex In silico (computational) methods for predicting environmental fate, (eco)toxicity.

Since 1976, the Global Environment Monitoring System – Food Contamination Monitoring and Assessment Program, which is commonly known as GEMS/Food, has informed governments, the Codex Alimentarius Commission and other relevant institutions, as well as the public, on levels and trends of chemical contaminants in food and their contribution to dietary exposure. The GEMS/Food Program is implemented by the WHO in cooperation with a network of WHO Collaborating Centres and national institutions located in many countries around the world. Main areas of activities of the GEMS/Food program include, among other data, more than 160 000 analytical results on the occurrence of about 300 chemicals in food from more than 40 countries and regions. EFSA collects data from publicly available sources such as peer-reviewed papers published in scientific journals, official national reports from European Member States or other sources. To complement these open data sources, EFSA regularly launches a call for data on occurrence of the substance(s) of interest and collects food consumption data. In response to these calls, mainly competent authorities of European Member States, but also other stakeholders, submit occurrence data in a specific format as requested by EFSA. Moreover, the EFSA Journal publishes all the opinions provided by the Scientific Committee and Panels. The opinions of the European Scientific Committees on food and feed can be traced back in the documents gathering the opinions adopted by these Committees, whereas the JECFA opinions, IARC monographs and EC documents, which may also provide relevant information, can be retrieved on the respective websites. EUR-Lex provides direct free access to EU law through consultation of the Official Journal of the EU. See Appendix A

It is currently possible to access the full list of chemical substances produced in the EU and, depending on volumes manufactured/imported, their use modalities and many physico-chemical properties following the adoption of Regulation (EC) 1907/2006 of the European Parliament and of the Council of 18 December 2006. The particular importance of this Regulation is that it enables a global and systematic approach to the identification of emerging issues and risks associated with industrial chemicals. The REACH Regulation has established a single system for data provision by manufacturer/importer companies for both “existing” (i.e. “phase-in substance”) and “new” substances (i.e. “non-phase-in”). A pre-registration of all “phase-in” substances manufactured or imported in quantities of 1 ton or more per year, including intermediates without limitation, has been requested within a time period starting on 1 June 2008 and ending on 1 December 2008, by sending the relevant information to the ECHA. The six months REACH pre-registration period closed on 1 December 2008. EU/European Economic Area-based companies submitted well over two million pre-registrations covering more than 100 000 substances. Moreover, any manufacturer or importer of a substance, either on its own or in one or more mixture(s), in quantities of 1 ton or more per year has been requested to submit a full registration to the ECHA. Similarly, any producer or importer of articles (e.g. manufactured goods such as cars, textiles and electronic chips) had to submit a registration to the agency for any substance contained in those articles, if both the following conditions are met: (a) the substance is present in those articles in quantities totalling over 1 ton per producer or importer per year; (b) the substance is intended to be released under normal or reasonably foreseeable conditions of use. In terms of data to be provided by manufacturers/importers of substances other than intermediates, different deadlines apply depending especially on the yearly amount of substance manufactured or imported. The registration obligation includes a technical dossier and, for all substances subject to registration in quantities of 10 tons or more per year per registrant, a chemical safety report. For additional information on the contents and structures of the REACH Registered Substances Information and the other databases see the Appendix B.

2.4.

Nanomaterials/Engineered Nanomaterials

Risks of nanomaterials are related to their specific structural characteristics and their specific uses. Due to the broad applications of engineered nanomaterials outside of foods and feeds and their possible environmental implications, it is necessary to pay consideration to how these materials are produced, used and disposed of, or recycled across the entire life-cycle of a product.


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As also indicated by several EFSA opinions (EFSA, 2009, 2011a, 2012a), EFSA has devoted special attention to safety of nanomaterials in the food and feed chain.

2.4.1.

Nanomaterials legislation status with respect to the REACH Regulation

Although the REACH Regulation does not contain specific requirements for nanomaterials, the Regulation applies to substances, regardless of their size or form, and therefore is considered to also apply to nanomaterials as well. With respect to the REACH requirements for nanosafety, from February 2012 to January 2013, a voluntary tick box “nanomaterial” was indicated in 7 registrations, and 18 notifications. However, many more registered substances are nanomaterials. Registration dossiers are generally unclear whether and how they cover nanomaterials. Therefore, the EC has concluded that more specific requirements in REACH Annexes are necessary and an impact assessment is being conducted for registration of nanomaterials below REACH tonnage, to identify and develop the most adequate means to increase transparency and ensure regulatory oversight, including an in-depth analysis of the data gathering needs for such purpose. This analysis will include those nanomaterials that fulfil the criteria for classification as hazardous under Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures. Many of the related provisions, including safety data sheets and classification and labelling already apply now, independently of the tonnage. Substances, including nanomaterials, meeting the classification criteria as hazardous and put on the market, must be notified to ECHA. ECHA has published advice on how to enter nanomaterial information in the International Uniform Chemical Information Database (IUCLID), and updated IUCLID 5.5 (2 April 2013) to include 13 new OECD agreed physico-chemical properties templates for nanomaterials. The table of terms and guidance for nanomaterials has also been updated, on the basis of the final reports from REACH Implementation Projects on Nanomaterials (RIP-oN2 Information requirements and RIP-oN3 Chemicals safety assessment) and the Commission Recommendation on the definition of “nanomaterial”. ECHA and EU Member States have also included some substances with nanoforms in the Community Rolling Action Plan (CoRAP) list of substances to be evaluated in 2012-2014. The classification and labelling Inventory and the web portal on “Registered substances of ECHA” also contain information on nanoform substances. The EC envisages modifications in some of the REACH Annexes and encourages ECHA to further develop guidance for registrations after 2013. If appropriate, the EC will come forward with a subsequent draft implementing act21. Best practices on the physico-chemical and substance identity information for nanomaterials are being collected from registrants that have registered nanomaterials and are published on the ECHA website22.

2.4.2.

OECD activities on nanomaterials

In 2006, the OECD launched a programme of work to analyse the potential safety concerns and to coordinate and harmonise international approaches for hazard, exposure and risk assessment for manufactured nanomaterials. In 2012, the OECD and its member countries have come to the same conclusion as the EC that the approaches for the testing and assessment of traditional substances are in general appropriate for assessing the safety of nanomaterials, but may have to be adapted to the specificities of nanomaterials. The OECD has concluded that in some cases, it might be necessary to adapt methods of sample preparation and dosimetry for safety testing (OECD, 2012). Similarly, adaptations may be needed for certain Test Guidelines. However, OECD does not consider it necessary to develop completely new approaches for nanomaterials. A review of all existing methodologies to identify and implement the necessary changes to the Test Guidelines that might be needed for their application to nanomaterials, and a number of workshops are planned in the near future to build a basis for this. More information on nanomaterials can be found

in Appendix C.

21

Available at: http://ec.europa.eu/enterprise/sectors/chemicals/reach/nanomaterials/ Nanomaterials report, available at: http://ec.europa.eu/environment/chemicals/nanotech/index.htm; Guidance on information requirements and chemical safety assessment for nanomaterials: http://echa.europa.eu/web/guest/guidance-documents/guidance-oninformation-requirements-and-chemical-safety-assessment. http://echa.europa.eu/documents/10162/5399565/best_practices_physiochem_subst_id_nano_en.pdf 22


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2.5.

In silico (computational) methods for predicting environmental fate and (eco)toxicity23

The chemical structure of a compound carries a lot of information on a wide range of physico-chemical aspects that ultimately determine its properties, behaviour, and biological activity. Combining this information with experimental data on a large number of tested compounds has led to different computational approaches that can provide estimates for physico-chemical properties, environmental fate and behaviour, toxicokinetic properties and (eco)toxicological effects of other yet untested chemicals. Collectively termed as in silico methods, these comprise molecular modelling tools; structure activity relationships (SAR) upon which physico-chemical read-across and chemical categories are based; predictive statistical models such as (Quantitative) Structure Activity Relationships ((Q)SARs); toxicity databases; and rule-based expert systems. These computational tools often only require chemical structure, and/or a few physico-chemical properties, as an input to provide a rapid means for screening of untested substances without the need for lengthy and costly toxicological animal tests. They are, therefore, helpful tools within the procedure for identifying emerging risks for the food chain from those chemical substances that have not yet been tested for safety to human health or the environment. A summary overview figure is presented in Appendix A. A usual work flow would be to first examine existing data and information, then see if one can conduct read across and grouping, using for example the OECD QSAR Toolbox and the data bases therein. A parallel step would also be to screen using QSARs with an appropriate applicability domain (Figure 2). A subsequent step to increase information could be to use metabolism prediction tools such as the expert systems METEOR (LHASA), TIMES and those available in the OECD QSAR toolbox, with the knowledge that such tools have been found to over generate potential metabolites. The US EPA MetaPath pesticide database will be also utilisable for metabolism simulation, when it is sufficiently well populated (US EPA, 2013). Requiring a high level of training and expertise, molecular modelling tools can also be used to conduct 3-D docking studies in potential target receptors and enzymes for the chemical in question, and the data generated can be used to build QSAR models. Computational network, systems biology and decision analysis approaches can be utilised to explore potentially adverse outcome pathways for the substance, as well as for ranking toxicity.

Figure 2:

In silico tools work flow for chemical hazard screening.

While the regulatory acceptance of in silico tools is currently limited, they are useful for (pre)screening purposes, as part of integrated approaches to testing and assessment, or when designing an integrated testing strategy. Extensive efforts are currently underway at the European and international levels to improve the

23

The list of software applications addressed in the present paper is not exhaustive. This report is not an EFSA endorsement of these applications.


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quality, reliability, use and integration of these tools. An example of the potential application of computational toxicology approach is discussed in a recent EFSA Opinion on endocrine disruptors (EFSA, 2013a). Appendix A of the present report provides a more extensive description of the available in silico (computational) methods for predicting: (i) environmental fate (i.e. persistence and bioaccumulation) and transfer of chemicals into food; and (ii) toxicity. Although a wide range of computational tools is available that can provide means for rapid estimation of physico-chemical properties, fate and behaviour, toxicity and ecotoxicity of untested chemical substances, reliability of the predictions obtained is bound to vary between different models and expert systems. This is because each system will reflect the quality and variability of the data that were used to build it, and the way the model was developed, tested and validated. It also needs noting that the use of different in silico methods and tools requires a skilled and subjective approach which cannot be reduced to a “black box” system. A good level of understanding of chemistry, biochemistry and toxicology is essential for appropriate interpretation of the in silico estimates of the various toxicological endpoints. Furthermore, combining assessments from more than one (Q)SAR model with additional information from, e.g. structural alerts and read-across estimates using a Weight of Evidence (WoE) approach can improve the utility of these tools and increase overall reliability of the in silico assessment.

2.6.

Physiologically-based (PB) models

Once an organism is exposed to a chemical compound, either following intentional or unintentional exposure, the substance may be absorbed and distributed to various tissues and organs by blood flow, following which it can bind to different biological moieties such as proteins and receptors, undergo metabolism, or can be excreted unchanged in the urine or the faeces. For a given substance, the concentration versus time profiles in different tissues, or the amount of metabolites formed, are often used to predict internal dose of the chemical using physiologically-based toxicokinetic (TK)/pharmacokinetic (PK) models (PBTK, PBPK). The key principles and best practices for characterising and applying PB-PK models in risk assessment including case studies can be found in the report published in 2010, by the International Programme on chemical safety of the WHO (WHO, 2010). Generally speaking, PB-TK models are usually developed using non-compartmental or compartmental models. Non-compartmental models are based on statistical regression analysis of TK measurements versus time and a number of covariates and are often used for exploratory analyses, screening of potentially influential factors as well as the determination of sample size for further TK studies (Gerlowski and Jain, 1983; Bois et al., 2010). In contrast, compartmental models split the organism’s body into one/multiple anatomical compartments all connected to the blood circulatory system to form an integrated model and are suitable for refined analyses to generate population models for prediction purposes (Gerlowski and Jain, 1983). In practice, compartmental models are built using anatomical, physiological, biochemical and physico-chemical data structured in specifically designed databases. These compartmental models can then be further refined integrating population information using recent tools such as POPGEN, a virtual human population generator (Loizou and Hogg, 2011; Bois et al., 2010; McNally et al., 2013). In addition, when combining population PBTK models with toxicodynamic (TD)/toxicity data PB-TK-TD (PB-TK-TD) can be developed and these enable to predict, while integrating biological variability in these processes, the relationship between internal dose and the toxicity dose response (Bois et al., 2010). Over the last decades, a large number of PB-TK models have been developed for risk assessment purposes mostly for a large number of pharmaceuticals, environmental contaminants and pesticides for human risk assessment with few examples in other vertebrate and invertebrate species. Examples of human PB-PK models for environmental contaminants include human PB-TK models for acrylamide (Doerge et al., 2007), PFOA and PFOS (Loccizano et al., 2013) and cadmium developed by EFSA (EFSA CONTAM Panel, 2009; Amzal et al., 2009). Recently, Hinderlinter et al. (2011) developed a human PB-TK-TD model for the organophosphate, taking into account inter-individual variation in exposure and response and identifying the parameters that drive variation in toxicodynamic outcomes (brain and red blood cell acetylcholinesterase inhibition) by using sensitivity analysis. For other animal species, examples of TK models include PB-TK for the anti-diabetic drug repaglinide in the pig (Sjogren et al., 2012), for midazolam in four avian species (chicken, turkey, pheasant and quail) (Cortright et al., 2009). For metals and heavy metals recent examples include a PB-TK for water-borne cadmium and zinc accumulation in the carp (Van Campenhout et al., 2009) and a TK population model in terrestrial invertebrates for heavy metals (TK cell demography model(TKCD)) (Argasinski et al., 2012).


19


Software packages to develop these models range from user-friendly excel spread sheet interfaces to software using complex algorithms such as MC-Sim, PK-Sim, Berkeley Madonna, acslX, MATLAB or PK-BUGS using full Bayesian inference (Loizou and Hoggs, 2011). Overall, PB-TK and PB-TK-TD models can provide quantitative insights on TK and TD processes for the characterisation of emerging chemicals hazards. Together with the use of other in silico methods, they can provide a useful mean to estimate toxicological hazard and likely internal exposure of an untested chemical substance, and thus enable risk assessment in the absence of experimental data. So far, these models have not been used by regulatory authorities for this purpose because of a number of limitations including the need for detailed knowledge on TK/TD data to develop the models (which are often not available), and their resource intensiveness (since they require specialised expertise). However, it can be foreseen that PB-TK and PB-TK-TD models may be increasingly used in the future for identifying and characterising emerging chemical hazards in combination with other in silico tools such as QSAR, read across techniques and as more generic predictive tools become available (EFSA, 2013b).


20


3.

APPLICATION OF THE PROCEDURE: (I) INTENTIONALLY PRODUCED INDUSTRIAL CHEMICALS; AND (II) NON-INTENTIONALLY PRODUCED CHEMICALS AND SUBSTANCES OF NATURAL ORIGIN

The two main entry points for which the available databases are considered adequate are described in the following chapters. The main entry point related to industrial chemicals is described in Figure 3, whereas the procedure regarding non-intentionally produced substances and substances of natural origin is described in Figure 4. The procedure proposed for the identification of emerging chemical risks, highlighted in Figure 3, consists of seven selection steps, each requiring input from specific data sources. Only the substances that reach step 6 are considered to constitute “emerging issues” and those reaching step 7 as “emerging risks”. It is important to stress that the sequence in the application of the selection criteria proposed below is one of the several possible approaches, as other sequences might also be equally successful. In fact, the sequence in the use of inclusion/exclusion criteria needs to be altered according to the specific context and data availability to ensure that those criteria that can be applied on larger numbers of chemicals are used at the earliest possible stages in the selection procedure. Therefore, the sequence provided below may be applied in a different way in consideration of the specific context under which the selection is carried out and to the specific task pursued.

Figure 3: Inclusion and exclusion criteria relevant for the systematic screening of registered chemical substances to identify emerging issues and risks in the food/feed chain: industrial chemicals24,25.

3.1.

(I) Emerging risks associated with intentionally produced industrial chemicals 3.1.1.

1st entry point. The REACH list of industrial chemicals

There are currently (as of 2013) 7 884 unique chemical substances registered under REACH with 30 601 dossiers. Of these, 4 886 substances have been registered from 1st June 2008 by chemical companies by means of 28 111 dossiers as being produced/imported in the EU in amounts of one ton and more per year. Of these registrations, 4 132 concern “phase-in” substances (in total 26 477 dossiers) and 754 concern “non phase-in” 24 The sequence of the selection criteria included in this figure is only indicative as it depends largely on the specific context under which the selection is carried out and especially on the pursued task, the nature of the criterion and the available data. In general, criteria easier and quicker to be applied on larger numbers of chemicals should be used as soon as possible in the selection procedure. The timing of the application of the criteria will have to be assessed on a case by case. 25 Depending on the context and objectives, not all steps may be necessary.


21


substances (1 634 dossiers). The remaining were substances notified under Directive 67/548/EC and, therefore, also considered as registered. The registration includes, among others, the obligation to provide a technical dossier addressing: (i) the identity of the manufacturer(s) or importer(s); (ii) the identity of the substance; and (iii) a chemical safety report for all substances subject to registration in quantities of 10 tons or more per year per registrant. At present a full set of data is available for the substances which have been registered at the first relevant transitional deadline of December 2010 and for the new substances which have been registered up to now after 1st December 2008. For all the other substances which need to be registered by December 2013 or by December 2018, many data are already present in the IUCLID files system, but the full set of required data will become available only after the registration. Some indications about the hazardous substances can be derived from the ECHA classification and labelling inventory, a database that contains classification and labelling information given by manufacturers and importers of the substances classified as hazardous under the classification, labelling and packaging (CLP) Regulation EC 1272/2008 and/or to be registered under REACH Regulation. The accuracy of the information is not yet reviewed by ECHA. For the substances listed in the Annex VI of the Regulation, the harmonised classifications are reported. As a consequence the substances that are not classified as hazardous according to CLP and that are produced or imported in quantities less or equal to 1 ton/year are not present in this inventory. Registrants and notifiers can have access to the classification and labelling platform, a new online interactive communication tool, to get in contact with other companies that have submitted notifications or registrations for the same substance and share data and eventually agree on a common classification and labelling. In order to apply the methodology proposed herein, it is important to define first the overall context and objectives of the screening, e.g. general human population or specific human population groups or environmental targets, general health damage or specific toxicity endpoints as well as consideration of all existing industrial chemicals or only specific groups of chemicals. This will determine choices of the inclusion/exclusion criteria and the order in which they can be applied. This approach, thus, has a high degree of flexibility that allows to adapt it for different emerging chemical risk scenarios. The following sequence is, therefore, provided as an example that might be interesting for EFSA in view of its responsibility for food and feed safety at the EU level.

3.1.2.

1st screening step. Industrial chemicals with high volume

Entry point: REACH Registered Substances Information, including industrial chemicals produced/imported in the EU. Selection approach: Substances manufactured/imported in (very) high volumes have a higher likelihood to end up in the food and feed chain. In view of this, it is proposed that substances with manufacturing/import volume of less than 1 ton/year should be considered of low interest. For substances with manufacturing/import volumes equal or higher than 1 ton/year, it is suggested that the amount of the chemical produced/imported is used as a priority criterion for inclusion in the procedure (Figure 3). Data Sources: Relevant data sources are provided by REACH Regulation in terms of the amounts of substances produced yearly (see Table 3). Of the new registrations under REACH (notifications/registrations under Directive 67/548/EEC excluded), only 60 % were full registrations for specific substances (i.e. not including intermediates). Most of the full registrations were for substances produced at higher than 1 000 tons per year (calculated by summing the latest year values for actual tonnages in and converting it to a band) and most of them (> 85 %) for “phase-in” unique substances. It is suggested that the selection procedures may be tested stepwise starting from the chemicals produced in higher amounts and progressively smaller volumes down to 1 ton/year in subsequent iterations. Outcome: The list of high volume industrial chemicals produced in the EU. The suggestion of initially concentrating on high volume chemicals is essentially proposed as an approach to reduce stepwise the number of chemicals to consider in a process that should have an iterative nature. It is evident that even substances produced in smaller amounts may be characterised by a very high toxicity and, therefore, be of some interest in the present context. Different approaches, therefore, may be justified in relation to specific tasks to be pursued.


22


Table 3: Number of chemical substances produced in tonnages above defined thresholds (Source: REACH Registered Substances Information). Tonnage Band 100 000 000 – 1 000 000 000 tonnes per annum 10 000 000 – 100 000 000 tonnes per annum 1 000 000 – 10 000 000 tonnes per annum 100 000 – 1 000 000 tonnes per annum 10 000 – 100 000 tonnes per annum 1 000 – 10 000 tonnes per annum 100 – 1 000 tonnes per annum 10 – 100 tonnes per annum 1 – 10 tonnes per annum Intermediate use only TOTAL

3.1.3.

Substances 5 45 157 322 596 941 337 184 249 2 050 4 886

2nd screening step. Industrial chemicals with high volume and high dispersive use

Entry point: The list of high volume industrial chemicals produced in the EU. Selection approach: Substances likely to be used in a way that implies extensive release into the environment are more likely to reach the food/feed chain. Select substances likely to be released in the environment based on the environmental release category and exclude the 2 050 intermediates (see Table 3) as intermediates are, in general, transferred from one manufacturing plant to another and then transformed into final products. Therefore, the opportunity for being released into the environment is much lower for intermediates than for chemical substances intended for dispersive final uses. Data Sources: Relevant data sources are provided by the REACH Regulation in terms of information on the production and use(s) of the substance. This information should represent all the registrant's identified use(s) and may include the relevant use and exposure categories. Information on manufacture and use of the substances (REACH Regulation) include: •

Overall manufacture, quantities used for production of an article that is subject to registration, and/or imports in tons per registrant per year in: the calendar year of the registration (estimated quantity)

•

In the case of a manufacturer or producer of articles: brief description of the technological process used in manufacture or production of articles. Precise details of the process, particularly those of a commercially sensitive nature, are not required

•

An indication of the tonnage used for his own use(s)

•

Form (substance, mixture or article) and/or physical state under which the substance is made available to downstream users. Concentration or concentration range of the substance in mixtures made available to downstream users and quantities of the substance in articles made available to downstream users

•

Brief general description of the identified use(s); the REACH use descriptor system is very articulated through well-defined specific categories such as the descriptor list for 27 main process categories including PROC 1-use in closed process no exposure), PROC7-industrial spraying (workplace exposure) or PROC11-non-industrial spraying (general population exposure)

•

Information on waste quantities and composition of waste resulting from manufacture of the substance, the use in articles and identified uses

•

Uses advised against. Where applicable, an indication of the uses which the registrant advises against and why (i.e. non-statutory recommendations by supplier). This need not be an exhaustive list

Outcome: High volume industrial chemicals that are likely to be released in the environment.


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3.1.4.

3rd screening step

A. Industrial chemicals with high dispersive use, and persistent and bioaccumulative nature Entry point: High volume industrial chemicals likely to be released in the environment. Selection approach: Select substances characterised by environmental persistence and those which also have a potential for bioaccumulation. Among substances selected through the previous steps, substances which tend to persist in the environment and to bio-accumulate in aquatic, and/or, potentially terrestrial organisms have a higher likelihood to end up in the food/feed chain. Data Sources. Relevant data sources are provided by the REACH Regulation (see Annex III of Reg. (EC)1907/2006) and the e-ChemPortal for information on properties that make it possible to predict/assess the environmental behaviour (see Table 4 below and Table 6 in Appendix B). Table 6 in Appendix B lists a variety of physico-chemical properties which, depending on the amount registered, are expected to be characterised by increasing levels of detail. In cases where experimental data are not available, data obtained from the in silico models described in Appendix A should be applied. For this selection step, the Annex XIII of Reg. (EC) No.1907/2006 should be considered. It lays down the criteria for the identification of persistent, bio-accumulative and toxic substances (PBT substances), and very persistent and very bio-accumulative substances (vPvB substances), as well as the information that must be considered for the purpose of assessing the P, B, and T properties of a substance. However, it is important to note that: (i) the definition of persistent and very persistent substance according to the REACH approach (see Appendix B) is based mainly on their degradation half-life in marine, fresh or estuarine waters and sediments (the only additional parameter considered being degradation half-life in soil); (ii) the definition of bioaccumulative substances only refers to bioaccumulation in aquatic organisms.

Table 4: Information requirements referred to in article 10 of (EC) 1907/2006: persistence and bioaccumulation properties. Data to be provided for nonphase-in substances, and for phase-in sub-stances meeting one or both of the criteria specified in Annex III”26 Ready degradability Hydrolysis as a function of pH Adsorption/desorption screening Biotic degradation/soil simulation testing Biotic degradation/sediment simulation testing Bioaccumulation in aquatic species, preferably fish Bioaccumulation in aquatic species, preferably fish Methods of detection and analysis

1 tonne/year or more (since 31 May 2018)

10 tonnes/year or more (since 31 May 2018)

100 tonnes/year or more (since 31 May 2013)

1000 tonnes/year or more (since 31 November 2010)

Yes

Yes Yes Yes

Yes Yes Yes

Yes Yes Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

The usefulness of Annex XIII in the context of a procedure to identifying emerging risks in the food and feed chain needs to be validated as the metabolism and bioaccumulation in terrestrial plants and animal species may also be relevant. 26

ANNEX III - Criteria for substances registered between 1 and 10 tonnes, with reference to Article 12(1)(a) and (b): (a) substances for which it is predicted (i.e. by the application of (Q)SARs or other evidence) that they are likely to meet the criteria for category 1A or 1B classification in the hazard classes carcinogenicity, germ cell mutagenicity or reproductive toxicity or the criteria in Annex XIII; (b) substances: (i) with dispersive or diffuse use(s) particularly where such substances are used in consumer M3 mixtures or incorporated into consumer articles; and (ii) for which it is predicted (i.e. by application of (Q)SARs or other evidence) that they are likely to meet the classification criteria for any health or environmental hazard classes or differentiations under Regulation (EC) No 1272/2008.


24


In order to take into account terrestrial botanical and animal species, in addition to persistence and bioaccumulation in the aquatic environment and species, it is proposed that a confirmation step is adopted for persistent and bio-accumulative and vPvB substances aiming at also assessing persistence and bioaccumulation in other species that may be relevant for the food chain. To this end, the use of software models such as those used by the EFSA CONTAM Panel in the evaluation of the poly-brominated flame retardants (EFSA CONTAM Panel, 2012) has an interesting potential to identify chemicals characterised by high overall persistence and a high overall potential for bioaccumulation (see Appendix A). This is mainly due to the fact that distribution to biota and accumulation throughout the food chain is poorly understood, because of lack of relevant studies and adapted models (EAHC, 2012). When environmental persistence/bioaccumulation of chemical substances is assessed, it should be also considered that repeated occurrence in specific environmental compartments (e.g. water or soil) far away from manufacturing plants and waste disposal plants of particular industrial chemicals is another important indicator of high persistence and of dispersive uses, while repeated occurrence in biota clearly highlights a potential for transfer and, possibly, bioaccumulation in the food/feed chain. Outcome: Lists of high volume industrial chemicals characterised by highly dispersive use modalities, and likely to persist at different degrees in the environment and bioaccumulate in the biota (e.g. list of vPvB substances and list of PB substances). B. Industrial chemicals with high volume, high dispersive use, and high toxicity Starting point: The list high volume industrial chemicals characterised by highly dispersive use modalities. Selection approach: It is proposed to concentrate on substances for which there are sound specific indications of toxicity (i.e. carcinogenic, genotoxic, reprotoxic and/or chronically toxic for mammals and/or toxicity for fish and/or for birds or plants). However, depending on the specific context of the emerging risk identification process, it could be reasonable to focus on selected endpoints only by disregarding toxic endpoints considered of minor relevance (e.g. bird toxicity). In any case, it would be important to clarify the underlying reasoning for deciding on the priority attributed to specific toxicity endpoints. For the criteria based on toxicity moving to quantitative probabilistic considerations could be difficult in view of the likely limitations of quantitative toxicity data. Data Sources: Relevant data sources are provided from the REACH Registered Substances Information (see Appendix B and the e-ChemPortal in terms of relevant properties, as well as by the in silico models such as the OECD (Q)SAR Toolbox and the ecotoxicological models described in Appendix A). Outcome: The list of toxic chemicals characterised by high manufacturing/import volume, by highly dispersive use modalities and by genotoxic, reprotoxic, neurotoxic, or other toxic activity.


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3.1.5.

4th screening step. Toxic industrial chemicals with high volume, high dispersive use, high persistence and bioaccumulation (Combination of selection criteria 3.1.4.A. and 3.1.4.B)

Starting points: Lists of chemicals characterised by a specific degree of persistence and bioaccumulation and/or by specific toxic activities. Selection approach: There are several reasonable combinations of the properties related to persistence/bioaccumulation and of those related to toxicity, especially depending on the context under which the emerging risk identification procedure is carried out. For instance, if the objective is to identify emerging risks related to chemicals more likely contributing to increase cancer incidence among humans at the EU level through dietary exposure, it would be justified to select highly persistent and bio-accumulative substances which are genotoxic. Conversely, if the objective is to identify the emerging risks in a limited geographical area directly impacted by chemicals released from one or more industrial or chemical waste disposal plants, it would be appropriate also to include in the process genotoxic substances, not necessarily being very persistent and/or bioaccumulative27. Therefore, this step is more likely amenable to a probabilistic approach in the use of selection criteria. The selection of a specific toxicity end point could also be justified as a function of the context in which the emerging risk identification takes place (e.g. in case the focus of the emerging risks identification process is on a specific malformation, it would be reasonable to concentrate on reprotoxicity as the relevant end point). Another factor that may justify the adoption of higher or lower threshold values for persistence/bioaccumulation and/or specific toxicity endpoints could be related to the resources and time available for the identification of emerging risks. Therefore, it is essential that the overall context under which the procedure is applied is well defined and that the adopted selection criteria are adequately justified. Data sources: Data sources relevant for this step obviously consist of those already addressed in the previous steps 3.1.4A and 3.1.4B. The modulation of the data retrieved from the different data sources should also reflect whether the selection procedure is applied to specified local pollution sources of industrial chemical or it is carried out in a broader European context. Outcome: List of toxic industrial chemical substances likely to occur/accumulate in the environment.

3.1.6.

5th screening step. Excluding regulated toxic chemicals

Starting point: The list of toxic industrial chemicals likely to occur/accumulate in the environment. Selection approach: All the chemicals already regulated in the food/feed context or subject to specific monitoring programs in food or feed should be excluded as they have already been identified as deserving specific attention. It is important to exclude the substances for which maximum permissible levels in food/feed have already been established at the European level or which are prohibited for use in the food/feed chain. Moreover, substances authorised for use in the food/feed chain such as food additives, solvents or feed additives should also be excluded. Data sources: The relevant EU Regulations dealing with: measures to monitor certain substances and residues thereof in live animals and animal products28, undesirable substances in animal feed29, maximum levels of some contaminants in food30, pharmacologically active substances and their classification regarding maximum residue 27 It should also be pointed out that, depending on the specific context under which the emerging risk identification process takes place, even the entry list may need reconsideration (e.g. if applied to a specific geographical area known to be characterized by particular chemical manufacturing activities, it would be reasonable to start from the list of those specific chemicals as an entry point rather than from the whole REACH register). 28 Directives 96/22/EC and 96/23/EC. 29 Directive 2002/32/EC, as modified by Directive 2001/102/EC, that repealed Directive 1999/29/EC, amended and integrated by number of subsequent Directives and Regulations; Directive 2003/57/CE; Directive 2003/100/EC; Directive 2005/8/EC; Directive 2005/86/EC; Directive 2005/87/EC; Directive 2006/13/EC; Directive 2006/77/EC; Directive 2008/76/EC; Directive 2009/8/EC; Regulation 2009/219/EC; Directive 2009/124/EC; Directive 2009/141/EC; Directive 2010/6/EC; Rectified by 2003/57/EC. 30 Regulation (EC) No 2006/1881/EC as modified by several subsequent Regulations; Regulation (EC) No 93/315/EC; Regulation (EC) No 2006/1881/EC amended by Regulation (EC) No 2007/1126/EC; Regulation (EC) No 2008/565/EC; Regulation (EC) No 2008/629/EC; Regulation (EC) No 2010/105/EC; Regulation (EC) No 2010/165/EC; Regulation (EC) No 2011/420/EC; Regulation (EC) No 2011/1258/EC; Regulation (EC) No 2011/1259/EC; Regulation (EC) No 2012/594/EC.


26


limits in foodstuffs of animal origin31, plant protection products32, maximum residues levels of pesticides in or on food and feed of plant and animal origin33, data requirements for active substances34, fertilizers35, animal byproducts and derived products not intended for human consumption36,37, and certain samples and items exempt from veterinary checks at the border38. Moreover, the main group of substances regulated for use in the food/feed chain can be identified by consulting the existing legislation39. Outcome: The list of unregulated toxic chemicals likely to occur/accumulate in the environment. It should be noted that the exclusion of chemical substances regulated under the food packaging materials or flavourings legislations would not be appropriate. In fact, food packaging materials are mainly regulated through the adoption of acceptable migration levels of specific substances into packaged foodstuffs. However, when food packaging materials are released into the environment and enter the waste disposal chain, this safety assessment approach becomes irrelevant as it is only applicable to intact packaging. Moreover, in the case of flavourings, safety assessment is largely based on read-across for toxicity properties and on self-limiting modalities of use in food/feed; the relevance of these criteria for environmental contaminants is doubtful.

3.1.7.

6th screening step. Excluding chemical substances evaluated by the EU

This section deals with the exclusion of chemical substances evaluated by the European Commission Scientic Committees for Food/Feed and EFSA (i.e. selecting emerging issues). Starting point: The list of unregulated toxic chemicals likely to occur/accumulate in the environment. Selection approach: Exclude all the chemicals already evaluated by the European Commission SCs competent for food/feed, EFSA or other scientific bodies as they have already been identified as needing specific attention. Data sources: All the opinions of the European SC for food and feed can be traced back in the documents gathering the opinions adopted by these Committees, whereas the opinions of EFSA are available on the EFSA Journal. JECFA opinions, IARC opinions and CE opinions, which may also provide relevant information, can be retrieved on the respective websites. Outcome: The list of toxic chemicals likely to occur in the environment (and therefore likely to occur in the food/feed chain) that have not been regulated as contaminants in food/feed and neither evaluated by the European Commission SC for Food/Feed and/or EFSA or authorised for use in food/feed (i.e. emerging issues).

3.1.8.

7th screening step. Selecting substances identified as emerging issues and occurring in the food/feed chain (i.e. emerging risks)

Starting point: The list of toxic chemicals likely to accumulate in the environment (and therefore likely to occur in food/feed) that have not been regulated or authorised for use in food/feed and neither evaluated by the European Commission SC for Food/Feed, EFSA or other international risk assessment bodies (i.e. emerging issues). The opinions of the non-food SANCO Committees might also be relevant in this context and should receive attention.

31

Regulation (EC) No 2010/37/EC. Regulation (EC) No 2009/1107/EC. 33 Regulation (EC) No 2005/396/EC and subsequent modifications and integrations. 34 Regulation (EC) No 2011/544/EC implementing Regulation 2009/1107/EC. 35 Regulation (EC) No 2012/223/EC. 36 Regulation (EC) No 2009/1069/EC. 37 Regulation (EC) No 2011/142/EC implementing Regulation (EC) No 2009/1069/EC. 38 Commission Directive 97/78/EC. 39 Regulations (EC) No 2011/1129/EC, 2011/1130/EC and subsequent modifications; Commission Directive 2009/32/EC; Regulation (EC) No 2003/1831/EC; Regulation (EC) No 2008/1332/EC and amending Commission Directive 83/417/EC; Regulation (EC) No 1999/1493/EC; Commission Directive 2000/13/EC; Commission Directive 2001/112/EC; Regulation (EC) No 1997/258/EC; Regulation (EC) No 2006/1925/EC; Regulation (EC) No 2003/1829/EC; and Regulation (EC) No 1997/258/EC. 32


27


Selection approach: Substances that have passed the preceding selection steps, together with data showing a significant occurrence in the food/feed chain, would be those to be considered as identified to be associated with emerging risks. Data sources: The selection of emerging risks among the emerging issues identified can be carried out by making use of specific data sources and/or of data obtained through ad hoc monitoring activities. The consultation of specialised literature on occurrence of chemical substances in the food/feed chain by undertaking ad hoc literature searches may verify for which substances there is evidence for their occurrence in the food/feed chain. Considering, however, that results of monitoring programs are in general not published in the open literature, but only in the grey literature, another important tool in this respect is the ad hoc call for data. The existing ongoing call for data should be extended to meet the needs of the present approach. Member States, research institutions and any other stakeholder should be invited to submit data on the testing and detection in the food/feed chain of chemical substances identified as emerging issues. Member States should also be requested to encourage the active involvement of food and feed business operators in the submission of all available data to EFSA. The rules on use, disclosure and re-use of occurrence data in the area of substances in food and feed agreed by the Standing Committee on the Food Chain and Animal Health on 19 May 2010 are applicable for this data collection. Another possibility would be to undertake, under the leadership of the European Commission, targeted monitoring programs on the priority chemicals identified as emerging issues in the food/feed chain to ascertain their actual occurrence. Smart monitoring and assessment tools are needed as it is not practical or affordable to sample and analyse at sufficient spatial and temporal resolution for hundreds of individual chemicals that may occur within the food/feed chain. Outcome: Emerging risks associated with industrial chemical contaminants.

3.1.9.

Subsets of the 1st main entry point list. Specific lists of industrial chemicals with highly dispersive uses and some evidence of environmental persistence

The approach described in the previous Sections from 3.1.1. to 3.1.8 is a global one focused, in principle, on all the industrial chemicals registered under the REACH Regulation. However, it is important to consider that, in particular contexts depending on specific priority objectives and/or data availability, selected groups of industrial chemicals could be addressed as subsets of the 1st entry point with considerable advantages in terms of practicability and speed of the procedure due to the availability of additional data and possibility of avoiding or modulating the application of some specific previously-described screening steps. This would, for example, be the case when adopting as entry points lists of pharmaceutical or personal care chemicals already detected in the environment (e.g. water, soil, sediment and biota) as contaminants. Such lists might be developed by crossing data from REACH Register with those from data sources concerning the occurrence of emerging substances across Europe such as the Norman Network. Moreover, it should be also considered that several recent reviews/articles are available in the open literature describing the occurrence in different environmental compartments of chemicals released from pharmaceutical, personal care and food packaging products (Binderup et al., 2002; Castle et al., 1997; Clarke et al., 2011; Damant, 1999; EFSA, 2011b; Fauris et al., 1998; Grob et al., 1991; Sipilainen-Malm et al., 1997; Stuart et al., 2012; Vinggaard et al., 2000; Ziegleder, 2001). In case this approach is adopted, one or more of the previously-described selection steps may be omitted. In fact, in the above-mentioned examples, the dispersive use is evident and some degree of persistence is shown by their occurrence in different environmental compartments. Therefore, the focus of the emerging risk identification procedure in these cases should be on the more advanced selection steps and especially on the evaluation of the potential transfer from different environmental compartments to drinking water (EFSA, 2010) and on the distribution to biota and evidence of uptake of specific above-mentioned chemical substances by edible botanical species (Blackwell et al., 2011; Eggen et al., 2012; Wu et al., 2012). Obviously, the further consideration of the potential toxicity of the chemicals involved would also remain an essential step that could also benefit for some of the above-mentioned group of chemicals, e.g. pharmaceuticals, from additional available data sources.


28


3.1.10.

Identification of substances of very high concern within the REACH framework: differences with the approach proposed in the present paper for the identification of emerging risks in the food/feed chain

The identification of substances of very high concern (SVHC) which may require special control measures such as ad hoc case-by-case authorization is carried out according to REACH through a special procedure leading to inclusion in the Annex XIV of (EC) Regulation 1907/2006, i.e. the list of substances subject to authorization, in order to better control their effects and be replaced as soon as possible40. According to Regulation (EU) 253/2011, registrations of substances under Regulation (EC) No 1907/2006 that are not in accordance with the Annex to this Regulation shall be updated in order to comply with this Regulation no later than 19 March 2013. Another important recent development in this sector has been the EU General Court's conclusions which confirm the ECHA's approach in identifying PBTs and vPvBs as SVHC (ECHA/PR/13/11- 8 March 2013). The ruling confirms that ECHA's approach in identifying unknown, or variable composition, or of biological origin (UVCB)41 substances as well as other multi-constituent substances as PBTs42 or vPvBs43 on the basis of their constituent ingredients present in a concentration of 0.1 % or more is lawful. The Court also upheld that ECHA's decisions were proportionate and did not breach the principle of equal treatment. The Court further ruled that after a substance has been identified by ECHA as having PBT and/or vPvB properties, suppliers of these substances are legally required to update their safety data sheets with this information. It follows that all registrants of such substances will also need to update their chemical safety report with such information. It is to be noted that according to the REACH Regulation, companies that have already concluded in their chemical safety assessment that a substance meets the criteria for identification as a PBT/vPvB are required to update their safety data sheet with this information even if ECHA has not yet formally identified such substances as PBTs/vPvBs and included them in the Candidate List. Such developments are of major interest also for the approach to the identification of chemical emerging risks for the food/feed chain by EFSA. In fact, it means that the identification of substances meeting the criteria in the Annex XIII for PBTs and vPvBs substances has to be carried out by each registrant, thus considerably facilitating such a task. Using the criteria and procedures described above, a list of 54 substances has been proposed on 3 September 2012 and consultations have been on going in Authorities from Member States and ECHA and finalized by 19 October 201244. Previous lists for consultation, published between 30 June 2008 and 27 February 2012, include 91 substances and are accessible on the ECHA website45. To this end, ECHA has implemented a two tiered priority setting approach for its next recommendation(s) of substances to be included in Annex XIV. Tier 1 uses a scoring approach based on the criteria ‘Intrinsic properties (PBT/vPvB)’, ‘Volume’ (t/y supplied in the EU to uses in the scope of authorization) and ‘Wide-dispersive use’ (with the sub-criteria ‘site-numbers’(use) and ‘release’). Tier 2 considers the results of the scoring/ranking and complements them with regulatory effectiveness considerations to draw final conclusions on priorities of the substances on the Candidate List (ECHA, 2010). This directive was replaced in early 2009 by the new EU Regulation (EC) No 1272/2008 on classification, labelling and packaging of chemical substances and mixtures, the so-called CLP Regulation (EC, 2008). Annex XV reports for SVHC prepared by a Member State or the Agency, are available on the ECHA website. Interested parties have 45 days from the date of publication to provide comments to the Agency on the identification of the substance as SVHC as well as further information related to use, exposure, alternatives and risks. While this REACH approach shows that the REACH Registered Substances Information is, in fact, a useful source to retrieve essential data for the implementation of the procedure described in the previous chapters of the present report for emerging risks identification, it is evident that the approach previously described for the identification of emerging risks and that for the identification of SVHC are actually different both in their objectives and outcomes. The REACH approach on substances of high concern does not address specifically their occurrence in the food/feed chain, but aims at taking into account also concerns associated with exposures through routes other than the food/feed chain such as at the work place and in the environment. Moreover, the REACH approach rather than being focused on unknown or not regulated chemical substances in the food/feed chain to be classified as emerging issues/risks and thus deserving a full risk assessment, clearly aims at identifying substances for which the adoption of ad hoc Regulations would be appropriate. 40

Art. 59, Reg. (EC) 1907/2006 describes in detail the procedure for establishing a candidate list of substances for eventual inclusion in the list of substances subject to authorization. Available at: http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2007:136:0003:0280:en:PDF 41 http://echa.europa.eu/view-article/-/journal_content/title/eu-court-confirms-echa-pbt-assessment-of-substances#_edn1 42 http://echa.europa.eu/view-article/-/journal_content/title/eu-court-confirms-echa-pbt-assessment-of-substances#_edn2 43 http://echa.europa.eu/view-article/-/journal_content/title/eu-court-confirms-echa-pbt-assessment-of-substances#_edn3 44 http://echa.europa.eu/web/guest/proposals-to-identify-substances-of-very-high-concern 45 http://echa.europa.eu/web/guest/proposals-to-identify-substances-of-very-high-concern-previous-consultations


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Therefore, it would be inappropriate to consider all the SVHC identified through the REACH procedure as emerging risks under the EFSA definition, and the other way around. The reasoning behind such a statement becomes clear through a detailed consideration of the properties of the 138 substances currently under consideration for being included under such qualifications (for the amounts produced see the Table 5). About 38 % of these substances are carcinogenic and another 38 % are toxic for reproduction. Substances which are both carcinogenic and toxic for reproduction are about 10 % of the total number, whereas another 10 % consists of PBT and/or vPvB substances. From the above consideration, it appears that only a very few out of the 138 substances so far considered as candidate for being of “very high concern” (the exact number could become available only after the exclusion criteria will have been applied to the few PBT and vPvB substances) and none can be currently considered to be associated with an emerging risk for the food/feed chain on the basis of the data already gathered in this report. Therefore, it can be concluded that, although some selection criteria and data sources are common to both procedures, the two procedures and their relevant contexts and objectives, although being complementary, are likely to lead to different results.

Table 5: Manufacturing/import volumes of chemicals considered in the framework of the “high concern substances” within the REACH framework. Tonnage band 100 000 000 - 1 000 000 000 tonnes per annum 10 000 000 - 100 000 000 tonnes per annum 1 000 000 - 10 000 000 tonnes per annum 100 000 - 1 000 000 tonnes per annum 10 000 - 100 000 tonnes per annum 1 000 - 10 000 tonnes per annum 100 - 1 000 tonnes per annum 10 - 100 tonnes per annum 1 - 10 tonnes per annum Intermediate Use Only Not included in the list of registered substances Impossible to search in the list of registered substances (No id numbers) Confidential manufacturing/importing tonnage TOTAL

3.2.

Substances 0 0 3 8 14 24 12 17 4 16 25 7 4 138

(II) Emerging risks associated with non-intentionally produced chemicals and chemicals of natural origin

As no ”register” currently exists for non-intentionally produced chemicals and for chemicals of concern of natural origin, a different entry point than the REACH Register is needed to identify emerging issues/risks associated with these chemicals (Figure 4). A suitable “entry point” in this case is provided by lists of substances repeatedly reported to occur in environmental compartments such as water, soil, sediments and/or biota and, especially, in the emissions/effluents of industrial plants or waste disposal plants, as well as at primary production level and storage. These lists include both (intentionally and non-intentionally produced) industrial chemicals and chemicals of natural origin. As the identification of emerging risks associated with intentionally produced industrial chemicals has already been dealt with, any compound included in the REACH register should be excluded from the second main entry point. However, it would be important not to overlook such findings in the context of the procedure described so far, as it is expected that industrial chemicals characterised by high production volumes, dispersive uses and environmental persistence and bioaccumulation, should also be detected sooner or later in one or more environmental compartments. Similarly, substances repeatedly reported to occur in environmental compartments are likely characterised by high persistence.


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Figure 4: Inclusion and exclusion criteria relevant for the systematic screening of registered chemical substances to identify emerging issues and risks in the food/feed chain: non-intentionally produced substances and substances of natural origin46.

(

(4)

3.2.1.

2nd entry point. List of chemical substances reported to occur in the environment

This section deals with the list of chemical substances reported to occur in environmental compartments such as water, soil, sediments and/or biota in the emissions/effluents of industrial plants or waste disposal plants as well as at primary production level and storage. Several data sources are relevant in this context. The list of the NORMAN Network emerging substances (update approved 6 March 2011) consists of more than 700 substances classified according to the following categories: algal toxins, anti-corrosives, anti-foaming agents, anti-fouling compounds, antioxidants, biocides, bioterrorism/sabotage agents, complexing agents, detergents, disinfection by-products (drinking water), drugs of abuse, flame retardants, food additives, fragrances, gasoline additives, industrial chemicals, nanoparticles, perfluoroalkylated substances and their transformation products, personal care products, pesticides, pharmaceuticals, plasticizers, trace metals and their compounds, wood preservatives and other substances (see Appendix B). The EC Joint Research Centre has recently organised a large-scale sampling and monitoring program at 122 river stations and 164 groundwater sites in 27 European countries in order to obtain a pan-European wide perspective on the occurrence and levels of a range of organic substances, including many of those considered to be emerging chemical substances (Loos et al., 2009, 2010). Emerging chemical substances are those for whom the potential for adverse effects has only recently become apparent (in contrast, for example, to metals and organochlorines) and for which the understanding of the sources, emissions, levels and effects in the aquatic environment remains limited. Across the Joint Research Centre study, nearly 60 organic substances were investigated (Loos et al., 2009). The U.S. Geological Survey (USGS) Toxic Substances Hydrology (Toxics) Program and The Northern (Canadian) Contaminants Program (NCP), important initiatives aiming at conducting large-scale reconnaissance of new contaminants in selected Third Countries, are likely to provide additional data useful to identify substances which are emerging issues/risks not only in the European context.

46 The sequence of the selection criteria included in this figure is only indicative as it depends largely on the specific context under which the selection is carried out and especially on the pursued task, the nature of the criterion and the available data and structure of the software. In general, criteria easier and quicker to be applied on larger numbers of chemicals should be used as soon as possible in the selection procedure.


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3.2.2.

1st screening step. Selecting chemicals repeatedly detected in the environment

Entry point: List of substances detected in environmental compartments. Selection approach: Occurrence of a specific substance in more than one database or evidence of repeated occurrence in a specific database. Data sources: The same as for second main entry point. Outcome: List of chemicals repeatedly detected in the environment.

3.2.3.

2nd screening step. Excluding the industrial chemicals registered under REACH

Entry point: List of chemicals repeatedly detected in environmental compartments. Selection approach: Exclude substances already registered under the REACH Regulation. These substances are industrial chemicals to be screened for emerging issues and risks under the procedure described in Section 3.1. Data Sources: The REACH list of registered chemicals. Outcome: List of natural contaminants and non-registered chemical substances.

3.2.4.

Subsequent five screening steps

The five subsequent screening steps in this procedure are identical to the third, fourth, fifth, sixth and seventh screening step in the previous procedure with the main difference that the REACH Registered Substances Information is of no use in this case, and that the in silico models for predicting persistence/bioaccumulation, toxicity and other properties are likely to be more useful. The emerging issues and risks identified at step sixth and seventh, respectively, are those associated with natural contaminants and non-registered chemicals.

3.3.

Considerations on the sequential implementations of exclusion/inclusion criteria

Once the entry point has been defined, the order in which the different inclusion/exclusion criteria are applied has no practical impact on the final result of the overall selection procedure chosen for the identification of emerging issues/risks. However, the time and resources needed to apply the procedure may be considerably different depending on the order with which the different selection criteria are applied. Considering the large number of chemicals likely to be involved in the procedure, it would be more convenient to make use, at early stages of the selection process, of criteria which are easier and faster to apply to a large number of chemicals. These aspects should be addressed during the future testing phase of the procedure (see Section 4).


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4.

TESTING AND FURTHER IMPROVING THE PROPOSED PROCEDURE THROUGH A PILOT PROJECT

The procedure for identifying emerging chemical risks highlighted in this report needs to be further detailed and tested, preferably through a pilot project with the following objectives: (i) evaluating the accessibility of the different databases addressed herein and develop the necessary collaborative frameworks and actions required to make them as much as possible accessible; (ii) testing and validating the present procedure to investigate its feasibility and possible improvements and refinements; and (iii) developing, if possible, a software capable of efficiently handling the large amount of data involved. In view of the broad scope of the proposed procedure, various approaches to validate the procedure can be investigated. However, in view of EFSA’s mission, further development and testing of the proposed procedure should preferably be focused on the ability to identify new chemical hazards for which significant exposure is likely through the food/feed chain, both of humans and animal species, and no risk assessment is available. Moreover, the flexibility of the different inclusion/exclusion criteria, their possible deterministic and probabilistic applications and their sequences of use in the procedure should also be explored along with their impacts in terms of the outcomes, speed and resources demand for the procedure. During the pilot project, the accessibility of the different databases addressed herein should be established. All the above-mentioned databases are partially accessible, but whether full accessibility is needed for application of the proposed procedure has to be carefully checked and may require (or be considerably improved by) a collaboration between EFSA and authorities holding these databases. Even for fully accessible databases such as the Norman Network, it is important to clarify the quality of data as well as to carry out practical tests in order to make use of the available data in an optimal manner. It is important to decide the sequence of application of the specific inclusion/exclusion criteria during the procedure and, especially, which ones should be used deterministically or probabilistically. Moreover, possible interactions of different criteria adopted should also be taken into account. Testing the proposed procedure through a specific pilot project will allow EFSA to decide whether to arrange a wider consultation with the EFSA Panels and EU Member States competent Authorities to identify both additional relevant data sources, and to receive advice on specific chemicals to be included as “entry points” for the identification of emerging issues and risks in a more specific or an even broader context. It is recommended that in the pilot project two different approaches are tested to check, 1) to what extent data are already available for retrieval in the REACH Registered Substances Information, and 2) whether and to what extent the existing in silico models are useful for the procedure proposed in this report for the identification of emerging risks in the food/feed chain.

4.1.

Application of the procedure to selected chemicals recognized as food/feed contaminants

It is suggested that, as a first approach, a small group, consisting of about 20 industrial chemicals, that are already recognised/regulated as contaminants of the food/feed chain undergoes the procedure highlighted in this report. This would enable an assessment of the validity of the specified data sources and the selection criteria, and their combination, in terms of whether they are able to effectively identify these test chemical contaminants. This validation approach should also aim at verifying whether the currently available REACH software system allows to combine available data according to approaches that are different from those adopted in the REACH Regulation.

4.2.

Selected chemical substances registered under the REACH Regulation

The second approach should be based on the application of the procedure described in section 3.1 to identify emerging risks from a selected group of chemicals (about 100) chosen according to ECHA’s past experience, and see whether it would be possible to identify the likely presence in the food chain of so far undetected emerging risks. The validation of this approach could be achieved through the identification of specific chemicals which meet the criteria for being classified as emerging risks. The pilot project should aim at testing and improving the procedure in a reasonable and manageable timeframe (i.e. within 1 or 2 years). It is suggested that the approaches described above are followed for intentionallyEFSA supporting publication 2014:EN-547

33


manufactured/imported industrial chemicals. The most appropriate step forward would be for EFSA to contract out the tasks with the ECHA’s support and experience with intentionally-produced industrial chemicals and the REACH register. When deciding on outsourcing, EFSA should use an interactive approach so that EFSA can be effectively informed and can also provide suggestions throughout the whole process. Moreover, participation of some members of the Standing WG to support this activity would also be helpful in terms of providing continuous scientific advice to the contractor of the pilot study. Depending on the outcomes of the two above-mentioned validation approaches, it might be appropriate to consider undertaking a third validation approach by using, as an entry point, the list provided by the Norman Network. In this case, about 100 chemical substances repeatedly reported to occur in the environment which are unintentionally produced or of natural origin could be submitted to the procedure described in Section 3.2. of this report by making use of the described in silico models to estimate their persistence/stability in the environment, accumulation in food-producing organisms as well as toxicity.


34


CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS The overall framework and the procedures proposed in this report for identification of chemical emerging risks in the food/feed chain aim at developing a structured and integrated use of data and information already available for a variety of purposes. This is a flexible framework which has the potential to identify chemical substances likely to be associated with emerging risks in the food/feed chain, while attributing low priority to chemicals that are unlikely to pose emerging risks. Another feature of the framework is that it is also applicable, in principle, to chemicals with very limited data due to the availability of in silico modelling tools that can be used to predict, to some extent, toxic properties and environmental fate of chemicals. Moreover, in addition to identifying emerging risks according to EFSA’s definition, this methodology could also be used to establish an early alert system for new chemicals. This could inform on the need for an oversight on any major increase in the manufacturing/importation volumes of chemicals, especially highly toxic substances that are also able to persist in the environment and accumulate in food and feed. In this respect, it is noteworthy that many new chemicals are being manufactured/imported in the EU every year (e.g. about 3 000-4 000 chemicals during the last 5-6 years). Although not being the focus of the present report, it is also worthwhile noting that, in addition to the whole group of industrial chemicals registered under the REACH Regulation, the methodology addressed herein could also be applied, depending on data availability, to other groups of chemicals such as chemicals: (i) from local releases (e.g. from intense point sources, such as leaks or discharges from (industrial) facilities); and (ii) from multiple closely spaced releases, such as domestic septic systems and to relatively uniform releases that occur over broad areas with similar land-use practices, such as agricultural and residential land uses.

RECOMMENDATIONS The procedure for identifying emerging risks/issues highlighted in the present report needs to be further detailed, clarified in relation to specific elements and tested, preferably through a pilot project as described in Section 4. This pilot project should have the following objectives: (i) evaluating the accessibility of the different databases already addressed herein, and develop the necessary collaborative frameworks and actions required to make them as much as possible accessible and useful in the present context; (ii) test and validate the present procedure by applying the approaches described in the Section 4 to investigate the feasibility of the procedure, and to identify possible future improvements and refinements; (iii) developing, if possible, a software capable of efficiently handling the large amount of data involved. Based on the results of the above-mentioned pilot project, further steps can be foreseen to: •

consider additional data sources and selection criteria, and to refine those already identified

•

further check the accessibility of the different databases already addressed herein and develop the necessary collaborative frameworks and actions to make them fully accessible, if needed

•

develop a database and a software to apply efficiently and systematically the inclusion/exclusion criteria which characterise the different selection steps of the proposed methodology; and

•

take actions to implement the recommended methodology for the systematic identification of emerging chemical risks through the food/feed chain


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APPENDICES Appendix A. In silico (computational) methods for predicting environmental fate and (eco)toxicity. Appendix B. Databases available on chemical substances Appendix C. Nanomaterials


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ABBREVIATIONS BfRs

Brominated flame retardants

CLP

Classification, labelling and packaging

CMR

Carcinogenic, mutagenic and reprotoxic

CoRAP

Community Rolling Action Plan

EC

European Commission

ECHA

European Chemicals Agency

EEA

European Environment Agency

EPA

Environmental Protection Agency

IARC

International Agency for Research on Cancer

IUCLID

International Uniform Chemical Information Database

JRC

Joint Research Centre

OECD

Organisation for Economic Co-operation and Development

PAHs

Polyaromatic hydrocarbons

PCBs

Polychlorinated biphenyls

PFAs

Perfluoroalkyls

PFOS

Perfluorooctanesulfonic acid or perfluorooctane sulfonate

PB

Physiologically-based

PK

Pharmacokinetic

POPs

Persistent organic pollutants

PBT

Persistent, Bioaccumulative and Toxic (substances)

(Q)SAR (Quantitative) Structure Activity Relationship REACH Registration, Evaluation, Authorization and Restriction of Chemicals SVHC

Substances of Very High Concern

TD

Toxicodynamic

TK

Toxicokinetic

UVCB

Unknown, or variable composition, or of biological origin

vPvB

Very persistent and very bioaccumulative (substances)

WoE

Weight of Evidence


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