Monitoring and surveillance data for chemical risk assessment needs in EFSA: exploring available sources

EFSA Supporting PublicationsVolume 13, Issue 1 939E Technical reportOpen Access Annual report of the EFSA Scientific Network of Risk Assessment of Nanotechnologies in Food and Feed for 2015 European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 11 January 2016 https://doi.org/10.2903/sp.efsa.2016.EN-939 Published date: 11 January 2016 Question number: EFSA-Q-2015-00596 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References EFSA CEF Panel (EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids), 2014. Statement on the safety assessment of the substance silicon dioxide, silanated, FCM Substance No 87 for use in food contact materials. EFSA Journal 2014; 12(6):3712, 7 pp. doi:10.2903/j.efsa.2014.3712 EFSA Scientific Committee, 2011. Scientific Opinion on Guidance on the risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain. EFSA Journal 2011; 9(5):2140 [ 36 pp.] doi:10.2903/j.efsa.2011.2140. Available online: http://www.efsa.europa.eu/ sites/default/files/scientific_output/files/main_documents/2140.pdf JRC, 2015: JRC science for policy report. Joint Research Centre. Towards a review of the EC Recommendation for a definition of the term "nanomaterial". doi:10.2788/678452. Available at: http://publications.jrc.ec.europa.eu/repository/bitstream/JRC95675/towards%20review%20ec%20 rec%20def%20nanomaterial%20-%20part%203_report_online%20id.pdf RIKILT and JRC, 2014. Inventory of Nanotechnology applications in the agricultural, feed and food Sector. EFSA Supporting Publication 2014: EN-621, 125. Available online: http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/621e.pdf Volume13, Issue1January 2016939E ReferencesRelatedInformation

EFSA JournalVolume 6, Issue 10 838 GuidanceOpen Access Statement of EFSA on a study associating bisphenol A with medical disorders European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 24 October 2008 https://doi.org/10.2903/j.efsa.2008.838Citations: 2 Acknowledgement: This statement was prepared by the EFSA Unit on food contact materials, enzymes, flavourings and processing aids (CEF) and the Unit on Assessment Methodology (AMU). EFSA wishes to thank the following members of the CEF Panel for their scientific advice during the drafting of this statement: Jean-Claude Lhuguenot, Wim Mennes and Detlef Woelfle. Adoption date: 22 October 2008 Published date: 24 October 2008 Question number: EFSA-Q-2008-702 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Centers for Disease Control and Prevention (CDC). 2004. National Health and Nutrition Examination Survey Data 2003–04. Hyattsville, MD: US Dept of Health and Human Services, CDC; 2004. EFSA (2006). Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to 2,2-BIS(4-HYDROXYPHENYL) PROPANE (Bisphenol A). The EFSA Journal (2006), 428, 1– 75. www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620772817.htm Lang, I., Galloway, T., Scarlet, A., Henley, W., Depledge, M., Wallace R. and Melzer, D. 2008. Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults. Journal of the American Medical Association. 2008; 300(11): 1303– 1310 jama.ama-assn.org/cgi/content/full/300.11.1303 Citing Literature Volume6, Issue10October 2008838 ReferencesRelatedInformation

Food contact materials are all materials and articles intended to come directly or indirectly into contact with food. Before being included in the positive European "Union list" of authorized substances (monomers, other starting substances and additives) for plastic food contact materials, the European Food Safety Authority (EFSA) must assess their safety "in use". If relevant for risk, the safety of the main impurities, reaction and degradation products originating from the manufacturing process is also evaluated. Information on genotoxicity is always required irrespective of the extent of migration and the resulting human exposure, in view of the theoretical lack of threshold for genotoxic events. The 2008 EFSA approach, requiring the testing of food contact materials in three in vitro mutagenicity tests, though still acceptable, is now superseded by the 2011 EFSA Scientific Committee's recommendation for only two complementary tests including a bacterial gene mutation test and an in vitro micronucleus test, to detect two main genetic endpoints (i.e., gene mutations and chromosome aberrations). Follow-up of in vitro positive results depends on the type of genetic effect and on the substance's systemic availability. In this study, we provide an analysis of the data on genotoxicity testing gathered by EFSA on food contact materials for the period 1992-2015. We also illustrate practical examples of the approaches that EFSA took when evaluating "non standard" food contact chemicals (e.g., polymeric additives, oligomer or other reaction mixtures, and nanosubstances). Additionally, EFSA's experience gained from using non testing methods and/or future possibilities in this area are discussed. Environ. Mol. Mutagen. 58:361-374, 2017. © 2017 Wiley Periodicals, Inc.

The European Union (EU) is committed to transitioning toward a circular economy model, with food waste being one of the areas to be targeted. To close the loop of food waste generated during food processing and discarded at the retail or consumption phases, research and innovation parties proposed to valorize agro-food by-products to produce novel foods and food improvement agents (food additives, food enzymes, and food flavorings). In the EU, the authorization of such novel foods and food improvement agents is governed by different regulatory frameworks. A centralized safety assessment by the European Food Safety Authority (EFSA) is the prerequisite for their authorization through the so-called Union Lists. Up to December 2023, EFSA published 45 scientific opinions on the safety of novel foods, food enzymes, and food additives derived from by-products of plant and animal origin. The current study illustrates examples of these by-products for the production of novel foods or food improvement agents and the data requirements behind their respective safety assessments conducted by EFSA. In this review, applications on novel foods, food enzymes, and food additives received by EFSA were screened and analyzed to find the common scientific requirements and differences in terms of the safety evaluation of such products. Various by-products (i.e., corncobs, coffee husks, spent grains of barley and rice, grape pomace, pumpkin peels, bovine whey, eggshells, shrimp heads, and animal organs or tissues) were described in the applications as being processed (extraction, physical treatments, and chemical and enzymatic reactions) to obtain novel foods and food improvement agents. The heterogeneity and complexity of these products emphasize the challenge of their safety assessment, depending on the characteristics of each product. However, as this study shows, the scientific requirements underpinning their safety do not differ substantially in the different regulated product areas considered, with similar information needed to assess their safety in terms of identity, production process, compositional characterization, proposed/intended uses and exposure assessment, toxicological information, and allergenicity data. Additional nutritional information and data on the history of use are required in the case of novel foods.

European Food Safety Authority open access tools to estimate dietary exposure to food chemicals

The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide scientific advice to the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel was requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. These flavouring substances are listed in the Register, which was adopted by Commission Decision 1999/217/EC and its consecutive amendments. The JECFA has evaluated a group of 12 simple aliphatic sulphides and thiols at the 61st meeting and seven trisulphides in a group of simple aliphatic and aromatic sulphides and thiols at the 53rd meeting. One of the substances evaluated by the JECFA at its 61st meeting is not in the Register (spiro[2,4-dithia-1-methyl-8-oxabicyclo(3.3.0)octane-3,3'-(1'-oxa-2'-methyl)-cyclopentane], JECFA-no: 1296). Accordingly this consideration will deal with 18 JECFA evaluated substances. The Panel concluded that the 18 substances in the JECFA flavouring group of simple aliphatic sulphides and thiols are structurally related to the group of 66 aliphatic and alicyclic mono-, di-, and polysulphides with or without additional oxygenated functional groups evaluated by EFSA in the Flavouring Group Evaluation 08, Revision 1(FGE.08Rev1). The Panel agrees with the outcome of the application of the Procedure performed by the JECFA for eight of the 18 aliphatic sulphides and thiols [FL-no: 12.179, 12.198, 12.212, 12.238, 12.239, 12.255, 12.257 and 12.291]. For two tertiary thiols, 2-methyl-4-oxopentane-2-thiol [FL-no: 12.169] and 2-mercapto-2-methylpentan-1-ol [FL-no: 12.241], the Panel concluded that they should not be evaluated through the Procedure, as they are structurally related to three tertiary thiols evaluated in FGE.08Rev1 which could not be evaluated through the Procedure due to concern with respect to genotoxicity in vitro. For the eight tri- and polysulphides [FL-no: FL-no: 12.009, 12.013, 12.020, 12.023, 12.045, 12.074, 12.155 and 12.280] the Panel did not agree with the JECFA that appropiate studies were available for deriving NOAELs, and accordingly additional data are required for these eight substances. For two substances [FL-no: 12.045 and 12.155] the JECFA evaluation is only based on MSDI values derived from production figures from the USA. EU production figures are needed in order to finalise the evaluation of these substances. For one substance use levels have been provided by the Industry. For the remaining 17 substances use levels must be provided. These are needed to calculate the mTAMDIs in order to identify those flavouring substances that need more refined exposure assessment and to finalise the evaluation. In order to determine whether the conclusion for the 18 JECFA evaluated substances can be applied to the materials of commerce, it is necessary to consider the available specifications. Adequate specifications including complete purity criteria and identity are available for 10 of the 18 JECFA evaluated substances. For seven substances [FL-no: 12.009, 12.020, 12.045, 12.169, 12.238, 12.239 and 12.291] information on secondary components and/or composition of mixture is requested. For six substances [FL-no: 12.009, 12.020, 12.023, 12.045, 12.074 and 12.155] no solubility in ethanol and/or solubility in water is available. Finally, the European production volumes are not available for [FL-no: 12.045 and 12.155]. Thus, for 10 substances [FL-no: 12.009, 12.020, 12.023, 12.045, 12.074, 12.155, 12.169, 12.238, 12.239 and 12.291] the Panel has reservations (no European production volumes are available, preventing them to be evaluated using the Procedure, and/or information on specifications). For two substances [FL-no: 12.169 and 12.241] the Procedure should not be applied until adequate genotoxicity data become available and for eight substances [FL-no: 12.009, 12.013, 12.020, 12.023, 12.045, 12.074, 12.155 and 12.280] additional toxicity data are required. For the remaining five of the 18 JECFA evaluated simple aliphatic sulphides and thiols [FL-no: 12.179, 12.198, 12.212, 12.255 and 12.257] the Panel agrees with JECFA conclusion “No safety concern at estimated levels of intake as flavouring substances” based on the MSDI approach.

As materials intended to be brought into contact with food, food contact materials (FCMs) – including plastics, paper or inks – can transfer their constituents to food under normal or foreseeable use, including direct or indirect food contact. The safety of FCMs in the EU is evaluated by the European Food Safety Authority (EFSA) using risk assessment rules. Results of independent, health-based chemical risk assessments are crucial for the decision-making process to authorize the use of substances in FCMs. However, the risk assessment approach used in the EU has several shortcomings that need to be improved in order to ensure consumer health protection from exposure arising from FCMs. This article presents the use of meta-analysis as a useful tool in chronic risk assessment for substances migrating from FCMs. Meta-analysis can be used for the review and summary of research of FCMs safety in order to provide a more accurate assessment of the impact of exposure with increased statistical power, thus providing more reliable data for risk assessment. The article explains a common methodology of conducting a meta-analysis based on meta-analysis of the dose-effect relationship of cadmium for benchmark dose evaluations performed by EFSA.

The European Food Safety Authority (EFSA) asked the Scientific Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide scientific advice to the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel was requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary

The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide scientific advice to the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs in the Member States. In particular, the Panel was requested to consider the Joint FAO/WHO Expert Committee on Food Additives (the JECFA) evaluations of flavouring substances assessed since 2000, and to decide whether no further evaluation is necessary

Data generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF.

The European Food Safety Authority (EFSA) was asked to evaluate a new study provided by industry that reports on the bioavailability of aluminium from several aluminium compounds in the rat. EFSA was asked whether the scientific data provided by the study could trigger the revision of the safety evaluation performed by EFSA in 2008, for the different aluminium based food additives investigated in this report (in particular SALP acidic, also known as sodium aluminium phosphate, acidic form or E 541). In the new study, the oral bioavailability of aluminium was determined as the ratio of the fraction of radioactivity left in the carcass seven days after oral administration of the 26Al-labelled compound of interest over the fraction of radioactivity left in the carcass seven days after intravenous administration of 26Al-labelled aluminium citrate using accelerator mass spectrometry (AMS). The results from the study show that the oral bioavailability of aluminium from twelve different aluminium-containing compounds, including the food additives aluminium sulphate, Allura Red AC aluminium lake (FD&C red 40 aluminium lake) and sodium aluminium silicate, ranges from 0.02 to 0.21%, and therefore falls within the overall 10-fold range of previously reported oral bioavailability values for aluminium from aluminium containing compounds. In the case of the two sodium aluminium phosphates, SALP acidic and SALP basic (KASAL), and aluminium metal, the measurements were below the limit of detection by AMS. In conclusion, the new study does not provide any additional information on the bioavailability of aluminium from aluminium-containing compounds that could modify the conclusions reached in 2008 by the Panel on Food Additives, Flavourings, Processing Aids and Food Contact Materials. Therefore, EFSA concludes that this study does not give reason to reconsider the previous safety evaluation of aluminium-based food additives authorised in the European Union performed by EFSA in 2008.

Per- and polyfluoroalkyl substances (PFASs) pose significant public health concerns due to their environmental persistence, bioaccumulation, and ubiquitous presence in human biomonitoring (HBM) data, despite regulatory restrictions. This study establishes a deterministic pharmacokinetic model for perfluorooctanoic acid (PFOA), enabling the estimation of PFOA concentrations in major human organs, even at low doses. The model integrates accumulation and recirculation mechanisms of PFOA in hepatic and renal tissues, leveraging publicly available HBM datasets (e.g., HBM4EU, NHANES, literature) to reconstruct bodyweight-normalized intake levels. Importantly, due to the extremely low urinary excretion concentrations of PFOA, most datasets were derived from blood-based measurements, particularly serum while confirming urine as unreliable biomarker of exposure. The analysis underscores the effectiveness of regulatory efforts in reducing PFOA exposures, as evidenced by declining time-trends in estimated exposure levels in recent studies. Risk characterization ratios were calculated based on recommended limits set by the European Food Safety Authority (EFSA), the United States, and Australia. While EFSA's tolerable weekly intake (TWI) indicated a high risk, other regulatory limits suggested less concern about risk at these intake levels. These findings highlight the need for continuous re-evaluation of exposures and targeted studies to identify key determinants of PFOA exposure, informing future regulatory measures. The study emphasizes the critical role of physiologically based pharmacokinetic (PBPK) modeling, HBM data, and exposure reconstruction in advancing chemical risk assessment. These tools form a science-based framework integral to the Chemical Strategy for Sustainability (CSS), enabling accurate predictions of internal exposure levels, empirical validation of models, and robust assessments of real-world exposure scenarios. The integration of these approaches supports the CSS goals of minimizing chemical risks while promoting innovation, ultimately contributing to a sustainable and protective regulatory landscape for human health and the environment.

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

EFSA Supporting PublicationsVolume 19, Issue 5 E200505E Technical reportOpen Access Theme (concept) paper – Advancing the Environmental Risk Assessment of Chemicals to Better Protect Insect Pollinators (IPol-ERA) European Food Safety Authority (EFSA), Corresponding Author European Food Safety Authority (EFSA) SPIDO@efsa.europa.eu Correspondence:SPIDO@efsa.europa.euSearch for more papers by this authorDomenica Auteri, Domenica AuteriSearch for more papers by this authorGuilhem de Seze, Guilhem de SezeSearch for more papers by this authorYann Devos, Yann DevosSearch for more papers by this authorJulia Fabrega, Julia FabregaSearch for more papers by this authorClaudia Heppner, Claudia HeppnerSearch for more papers by this authorMarta Hugas, Marta HugasSearch for more papers by this authorSteve Pagani, Steve PaganiSearch for more papers by this authorAgnès Rortais, Agnès RortaisSearch for more papers by this author European Food Safety Authority (EFSA), Corresponding Author European Food Safety Authority (EFSA) SPIDO@efsa.europa.eu Correspondence:SPIDO@efsa.europa.euSearch for more papers by this authorDomenica Auteri, Domenica AuteriSearch for more papers by this authorGuilhem de Seze, Guilhem de SezeSearch for more papers by this authorYann Devos, Yann DevosSearch for more papers by this authorJulia Fabrega, Julia FabregaSearch for more papers by this authorClaudia Heppner, Claudia HeppnerSearch for more papers by this authorMarta Hugas, Marta HugasSearch for more papers by this authorSteve Pagani, Steve PaganiSearch for more papers by this authorAgnès Rortais, Agnès RortaisSearch for more papers by this author First published: 31 May 2022 https://doi.org/10.2903/sp.efsa.2022.e200505 Disclaimer: This document does not present future project calls as part of EFSA’s work programme, or any future position of EFSA. It aims to support the development of a roadmap for action and its content can be subject to change. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume19, Issue5May 2022E200505E RelatedInformation

In the context of the circular economy and the increasing demand for safe and sustainable packaging, this work addresses the safety assessment of food contact materials (FCMs) derived from agro-industrial by-products. Despite growing interest in these bio-based materials, the literature still lacks a structured safety-assessment framework able to account for substrate-related contaminants, microbial processing, and downstream impurities. The novelty of this work lies in applying the European Food Safety Authority (EFSA) Technical Report perspective on natural mixtures to two representative case studies: bacterial cellulose (BC) produced by Komagataeibacter spp., as a promising microbial biopolymer for food packaging application, and nisin produced by Lactococcus lactis subsp. lactis, as an antimicrobial peptide, to functionalize the packaging material. This study aims to evaluate whether the EFSA-oriented framework can support the identification of potential substances of concern across the production chain when cellulose is produced starting from agro-industrial waste or nisin is applied. For this, a systematic literature review (SLR) was conducted to investigate potential substances of concern from agro-industrial substrates through fermentation to the final activated materials. The findings highlight the need to characterize natural carbon sources, including pesticide residues, consider the qualified presumption of safety (QPS) status of production microorganisms, and assess metabolites and fermentation by-products. The behavior of these substances during processing and their potential migration into food are critical aspects. A preliminary safety assessment at early development stages is therefore essential to guide material design and regulatory compliance. Overall, this study provides a practical framework to support researchers, developers, and risk assessors in identifying safety concerns and improving the regulatory readiness of innovative bio-based FCMs.