European Food Safety Authority Guidance Research Articles

Energy Content, Moisture Content, and Energy Assimilation Efficiency by Birds and Mammals of Oil-Containing Seeds and Implications for Seed Treatment Risk Assessments for Birds and Mammals.

Energy content, moisture content, and energy assimilation efficiency are essential parameters in the food intake rate (FIR) and exposure calculations for bird and mammal risk assessments. The updated European Food Safety Authority guidance document on risk assessment for birds and mammals summarizes these parameters for different food items. For seed treatments, values for cereal seeds are proposed as surrogates for other crops. Oil-containing seeds are expected to have a higher energy content than cereal seeds. This would result in lower FIR and, thus, exposure from consuming such seeds. To be able to calculate reliable exposure values for risk-assessment purposes, we conducted a systematic literature review to collect information on these three parameters for oil-containing seeds (sunflower, oilseed rape, soybean, peanut, sesame, safflower, linseed [flax], white mustard, and castor bean). The search yielded 401 papers, of which 151 contained values for at least one of the parameters of the crops in focus. The overall average energy content value of oil-containing seeds was 24.25 kJ/g (n = 124, SD = 3.00), whereas that for moisture content was 6.57% (n = 296, SD = 1.15). Energy assimilation values were only available for peanut, oilseed rape, soy, linseed, and sunflower for a limited number of bird and mammal species. Mean energy assimilation efficiency for mammals was 82.69% (n = 4, SD = 1.55), whereas values for birds were 57.54% (n = 2, SD = 6.77) for Galliformes and 79.25% (n = 2, SD = 1.82) for Passeriformes. The values presented can be used to calculate appropriate FIR values for future bird and mammal risk assessments. Environ Toxicol Chem 2024;00:1-6. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach.

Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide-HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89-94% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers.

Examination of the endocrine-disrupting properties of “active chlorine generated from seawater by electrolysis” in response to the European Biocidal Products Regulation: current knowledge and methodological challenges

BackgroundCurrently, active chlorine is considered the most effective treatment for preventing biofouling of structures in contact with seawater. This compound falls under the scope of the EU Biocidal Products Regulation, which includes since 2018 a requirement to assess all active ingredients for their potential endocrine-disrupting properties on humans and non-target organisms. Therefore, this study examines the endocrine-disrupting (ED) potential of active chlorine based on the European Chemicals Agency and European Food Safety Authority guidance (ED TGD). It includes two approaches: (i) a systematic literature review using appropriate search terms and (ii) an in silico assessment, both supported by expert judgement. Finally, the feasibility and relevance of in vitro tests were examined by considering the stability of chlorine and the applicability domain of the recommended in vitro assays.ResultsNo significant adversity or endocrine activity based on EATS (estrogen, androgen, thyroid, and steroidogenesis)-modalities were evidenced based on the literature data. However, these modalities remain understudied and further datasets are needed for a comprehensive assessment. The in silico approach revealed a low probability of binding between active chlorine and a set of 14 human nuclear receptors, for both agonist and antagonist effects. This is not surprising given the great structural difference between active chlorine and natural ligands. The in vitro investigation of the ED potential of active chlorine raises several operational limits, including: (i) its instability (t1/2 < 48 h) which is incompatible with a reasonable time window between collection and ex situ analysis; (ii) its rapid and complete reaction with several essential nutrients in cell culture media; (iii) its documented cytotoxicity on various cell lines; and (iv) its exclusion from the scope of certain OECD guidelines.ConclusionsOverall, neither the in silico evaluation nor the systematic literature review performed indicates a significant adversity based on EATS-mediated parameters or EATS-related endocrine activities. This study highlights the challenges of performing a comprehensive ED assessment for a data-poor chemical and questions the relevance of transposing generic methodologies to the case of unstable and inorganic molecules.

A content analysis of the European food safety Authority’s scientific opinion on authorised and rejected appetite-related health claim applications

From 2006 to 2020, UK nutrition and health claims were assessed by the European Food Safety Authority (EFSA) under EU Nutrition and Health Claims Regulations (2006). Since Brexit, UK applications are considered by the UK Nutrition and Health Claims Committee (UKNHCC).EFSA guidance documentation drawing together claims related to appetite ratings, weight management, and blood glucose concentrations was most recently published in 2012. 61 EFSA scientific opinions on appetite-related health claims applications from 2010 to 2020 were reviewed. Fifty-five related to hunger, fullness, energy intake, satiation and satiety were rejected, whereas three weight management claims and three blood glucose levels claims were authorised. 17 novel categories of reasons for claims application rejection were synthesised via Inductive Content Analysis (7 main-, 10 sub-categories). The resultant conceptual framework presented herein aims to support commercial pre-assessment of future appetite-related health claim applications and stimulate discussion regarding appetite-related health claims legislation in the new era of UKNHCC.

Repercussions of politicized regulation exemplified by compulsory new TC1507-maize 90-day rat feeding study

Politicized and prescriptive regulation of genetically modified (GM) crops has unintended adverse effects, including misdirected resources and reduced benefits. In the case of animal testing, this suboptimal use of resources includes the needless sacrifice of animals. Whole-food animal feeding studies are generally of negligible value in the risk assessment of GM crops, a position that was affirmed by the European Food Safety Authority (EFSA). Contrary to EFSA’s 2011 position, in 2013, the European Commission directed that 90-day rat studies be conducted for new GM events. As no EFSA guidance was available for hypothesis-free 90-day rat feeding studies, EFSA interpreted this as a mandate to develop a prescriptive study design. Recently, EFSA has retroactively required 90-day rat studies be completed under new study guidelines for previously approved component single events as part of the approval of breeding stacks. Having been unable to secure a derogation (exemption) from EFSA, a new compulsory 90-day rat study was conducted with TC1507 maize to support a breeding-stack submission. As previously shown, TC1507 maize does not adversely affect rats. This politically driven additional animal testing is risk disproportionate, at odds with European and international standards for animal welfare, and provides no scientific value to the safety assessment for GM breeding stacks.

Draft Genome Sequences of Two Bacteriocin-Producing Enterococcus faecium Strains Isolated from Nonfermented Animal Foods in Spain.

Here, we report the draft genome sequences of two bacteriocin-producing Enterococcus faecium strains isolated from nonfermented animal foods in Spain. The genomes of the strains contain at least three different regions encoding bacteriocins, and the strains comply with the European Food Safety Authority guidance for use in animal nutrition.

Prevalence sample‐based guidance for reporting 2021 data

Prevalence sample-based data should be transmitted from European Union (EU) Member States (MSs) to the European Food Safety Authority (EFSA) using the EFSA Standard Sample Description version 2 (SSD2) standard. To support reporting countries in data transmission using eXtensible Markup Language (XML) data transfer, specific guidance is given in this report covering the reporting of sample-based zoonoses and zoonotic agent data. This guidance is specifically aimed at guiding the reporting of information under the framework of Directive 2003/99/EC, Regulation (EU) 2017/625, Commission Implementing Regulation (EU) 2019/627 and of Commission Delegated Regulation (EU) 2018/772. The objective is to explain in detail the individual data elements that are included in the EFSA (SSD2) data model to be used for the XML prevalence sample-based data transmission through the Data Collection Framework according to the protocol described in the EFSA Guidance on Data Exchange version 2 (GD2). In particular, data elements to be reported are explained, including information about the data type, a reference to the list of allowed terms and business rules or requirements that may apply.

Guidance for reporting 2021 avian influenza data

Avian influenza surveillance data should be submitted twice a year from Member States to the European Food Safety Authority (EFSA) using the EFSA Standard Sample Description version 2 (SSD2). Specific guidelines to support reporting countries with this data transmission (using eXtensible Markup Language (XML) data transfer) are given in this report. The objective of this report is to explain in detail the individual data elements that are included in the EFSA (SSD2) data model used for reporting Avian Influenza (AI) surveillance data. These data elements should be used for reporting laboratory testing results via the EFSA Data Collection Framework, and according to the protocol described in the EFSA Guidance on Data Exchange version 2. A full description of the data elements including information about the data type are presented. Further, a list of allowed terms and business rules or requirements that apply are shown.

Statement of the PPR Panelon a framework for conducting the environmental exposure and risk assessment for transition metals when used as active substances in plant protection products (PPP).

The European Commission asked the European Food Safety Authority (EFSA) to prepare a statement on a framework for the environmental risk assessment (ERA) of transition metals (e.g. iron and copper) used as active substances in plant protection products (PPPs). Non‐degradability, essentiality and specific conditions affecting fate and behaviour as well as their toxicity are distinctive characteristics possibly not covered in current guidance for PPPs. The proposed risk assessment framework starts with a preliminary phase, in which monitoring data on transition metals in relevant environmental compartments are provided. They deliver the metal natural background and anthropogenic residue levels to be considered in the exposure calculations. A first assessment step is then performed assuming fully bioavailable residues. Should the first step fail, refined ERA can, in principle, consider bioavailability issues; however, non‐equilibrium conditions need to be taken into account. Simple models that are fit for purpose should be employed in order to avoid unnecessary complexity. Exposure models and scenarios would need to be adapted to address environmental processes and parameters relevant to the fate and behaviour of transition metals in water, sediment and soils (e.g. speciation). All developments should follow current EFSA guidance documents. If refined approaches have been used in the risk assessment of PPPs containing metals, post‐registration monitoring and controlled long‐term studies should be conducted and assessed. Utilisation of the same transition metal in other PPPs or for other uses will lead to accumulation in environmental compartments acting as sinks. In general, it has to be considered that the prospective risk assessment of metal‐containing PPPs can only cover a defined period as there are limitations in the long‐term hazard assessment due to issues of non‐degradability. It is therefore recommended to consider these aspects in any risk management decisions and to align the ERA with the goals of other overarching legislative frameworks.

Prevalence sample‐based guidance for reporting 2020 data

Prevalence sample-based data should be transmitted from Member States to the European Food Safety Authority (EFSA) using the EFSA Standard Sample Description version 2 (SSD2) standard. To support reporting countries in data transmission using eXtensible Markup Language (XML) data transfer, specific guidance is given in this report covering the reporting of sample-based zoonoses and zoonotic agent data. This guidance is specifically aimed at guiding the reporting of information under the framework of Directive 2003/99/EC, Regulation (EU) 2017/625, Commission Implementing Regulation (EU) 2019/627 and of Commission Delegated Regulation (EU) 2018/772. The objective is to explain in detail the individual data elements that are included in the EFSA (SSD2) data model to be used for the XML prevalence sample-based data transmission through the Data Collection Framework according to the protocol described in the EFSA Guidance on Data Exchange version 2 (GD2). In particular, data elements to be reported are explained, including information about the data type, a reference to the list of allowed terms and business rules or requirements that may apply.

Evaluating plant residue decline data with KinGUII and TREC: results from case studies involving also non-SFO kinetic models

BackgroundFoliage residue decline data are used to refine the risk assessment for herbivorous birds and mammals foraging in fields treated with plant protection products. For evaluation, current EFSA guidance has a clear focus on single-first order (SFO) kinetic models. However, other kinetic models are well established in other areas of environmental risk evaluations (e.g., soil residue assessment), and easy-to-use calculation tools have become available now. We provide case studies with 6 fungicides how such evaluations can be conducted with two of these tools (KinGUII and TREC) that have been developed by Bayer.ResultsSFO kinetics provided the best fits only for 13 of 36 residue decline studies conducted in a standardized design under field conditions. Biphasic models (double first order in parallel, hockey stick) were often superior and sometimes more conservative for risk assessment. The additional effort is manageable when using software such as KinGUII and TREC, and appears justified by the more reliable outcome of the evaluations.ConclusionsFurther research would be useful to better assess the extent to which non-SFO better fits foliage residue decline, but our study suggests that it may be a significant proportion. Therefore, we encourage the use of biphasic models in the regulatory risk assessment for herbivorous birds and mammals, in the ongoing revision of the European Food Safety Authority (EFSA) guidance document from 2009.

Novel foods in the European Union: Scientific requirements and challenges of the risk assessment process by the European Food Safety Authority

The European Food Safety Authority (EFSA) has been involved in the risk assessment of novel foods since 2003. The implementation of the current novel food regulation in 2018 rendered EFSA the sole entity of the European Union responsible for such safety evaluations. The risk assessment is based on the data submitted by applicants in line with the scientific requirements described in the respective EFSA guidance document.The present work aims to elaborate on the rationale behind the scientific questions raised during the risk assessment of novel foods, with a focus on complex mixtures and whole foods. Novel foods received by EFSA in 2003–2019 were screened and clustered by nature and complexity. The requests for additional or supplementary information raised by EFSA during all risk assessments were analyzed for identifying reoccurring issues.In brief, it is shown that applications concern mainly novel foods derived from plants, microorganisms, fungi, algae, and animals. A plethora of requests relates to the production process, the compositional characterization of the novel food, and the evaluation of the product’s toxicological profile. Recurring issues related to specific novel food categories were noted.The heterogeneous nature and the variable complexity of novel foods emphasize the challenge to tailor aspects of the evaluation approach to the characteristics of each individual product. Importantly, the scientific requirements for novel food applications set by EFSA are interrelated, and only a rigorous and cross-cutting approach adopted by the applicants when preparing the respective application dossiers can lead to scientifically sound dossiers. This is the first time that an in-depth analysis of the experience gained by EFSA in the risk assessment of novel foods and of the reasoning behind the most frequent scientific requests by EFSA to applicants is made.

Biosafety of GM Crop Plants Expressing dsRNA: Data Requirements and EU Regulatory Considerations.

The use of RNA interference (RNAi) enables the silencing of target genes in plants or plant-dwelling organisms, through the production of double stranded RNA (dsRNA) resulting in altered plant characteristics. Expression of properly synthesized dsRNAs in plants can lead to improved crop quality characteristics or exploit new mechanisms with activity against plant pests and pathogens. Genetically modified (GM) crops exhibiting resistance to viruses or insects via expression of dsRNA have received authorization for cultivation outside Europe. Some products derived from RNAi plants have received a favourable opinion from the European Food Safety Authority (EFSA) for import and processing in the European Union (EU). The authorization process in the EU requires applicants to produce a risk assessment considering food/feed and environmental safety aspects of living organisms or their derived food and feed products. The present paper discusses the main aspects of the safety assessment (comparative assessment, molecular characterization, toxicological assessment, nutritional assessment, gene transfer, interaction with target and non-target organisms) for GM plants expressing dsRNA, according to the guidelines of EFSA. Food/feed safety assessment of products from RNAi plants is expected to be simplified, in the light of the consideration that no novel proteins are produced. Therefore, some of the data requirements for risk assessment do not apply to these cases, and the comparative compositional analysis becomes the main source of evidence for food/feed safety of RNAi plants. During environmental risk assessment, the analysis of dsRNA expression levels of the GM trait, and the data concerning the observable effects on non-target organisms (NTO) will provide the necessary evidence for ensuring safety of species exposed to RNAi plants. Bioinformatics may provide support to risk assessment by selecting target gene sequences with low similarity to the genome of NTOs possibly exposed to dsRNA. The analysis of these topics in risk assessment indicates that the science-based regulatory process in Europe is considered to be applicable to GM RNAi plants, therefore the evaluation of their safety can be effectively conducted without further modifications. Outcomes from the present paper offer suggestions for consideration in future updates of the EFSA Guidance documents on risk assessment of GM organisms.

Physical, chemical, and toxicological characterization of fibrillated forms of cellulose using an in vitro gastrointestinal digestion and co-culture model.

Fibrillated cellulose is a next-generation material in development for a variety of applications, including use in food and food-contact materials. An alternative testing strategy including simulated digestion was developed to compare the physical, chemical, and biological characteristics of seven different types of fibrillated cellulose, following European Food Safety Authority guidance. Fibrillated forms were compared to a conventional form of cellulose which has been used in food for over 85years and has Generally Recognized as safe regulatory status in the USA. The physical and chemical characterization of fibrillated celluloses demonstrate that these materials are similar physically and chemically, which composed of the same fundamental molecular structure and exhibit similar morphology, size, size distribution, surface charge, and low levels of impurities. Simulated gastrointestinal and lysosomal digestions demonstrate that these physical and chemical similarities remain following exposure to conditions that mimic the gastrointestinal tract or intracellular lysosomes. A toxicological investigation with an advanced intestinal co-culture model found that exposure to each of the fibrillated and conventional forms of cellulose, in either the pristine or digested form at 0.4% by weight, showed no adverse toxicological effects including cytotoxicity, barrier integrity, oxidative stress, or inflammation. The results demonstrate the physical, chemical, and biological similarities of these materials and provide substantive evidence to support their grouping and ability to read-across data as part of a food safety demonstration.

Harmonised collection of national food consumption data in Europe

Since 2005, the European Food Safety Authority (EFSA) has worked in close cooperation with organisations operating in the field towards harmonising dietary survey methodology and building a common European Union (EU) food consumption database. Harmonised food consumption data are the basis for improving accuracy of EU-wide exposure assessments and also supports nutrition surveillance, diet and health related studies. Improved risk assessments assure more targeted risk management and permit more accurate risk communication resulting in increased consumer confidence. The most important step in this direction was the development of the EFSA Comprehensive European Food Consumption Database, which compiles existing national dietary information from the Member States (MS). MS used different methods to collect food consumption data, which makes it difficult to carry out EU-wide analyses or country-to-country comparisons. Furthermore, as the consumption patterns are continuously changing, regular update of the available information is necessary. Therefore, in 2011 EFSA launched the “What’s on the Menu in Europe? - EU Menu” project, with the aim of providing financial and technical support to carry out national dietary surveys in the EU. It focuses on collecting data from six population groups (from three months to 74 years of age) using harmonised methods described in the EFSA Guidance on the EU Menu methodology that has been endorsed by the EU institutions through the EFSA Network on Food Consumption Data. EFSA is currently supporting 36 surveys on children and/or adults from 18 Member States and four pre-accession countries. All projects are expected to be finalised by 2023.

Guidance for reporting 2020 avian influenza data

Avian influenza surveillance data should be submitted twice a year from Member States to the European Food Safety Authority (EFSA) using the EFSA Standard Sample Description version 2 (SSD2). Specific guidelines to support reporting countries with this data transmission (using eXtensible Markup Language (XML) data transfer) are given in this report. The objective of this report is to explain in detail the individual data elements that are included in the EFSA (SSD2) data model used for reporting Avian Influenza (AI) surveillance data. These data elements should be used for reporting laboratory testing results via the EFSA Data Collection Framework, and according to the protocol described in the EFSA Guidance on Data Exchange version 2. A full description of the data elements including information about the data type are presented. Further, a list of allowed terms and business rules or requirements that apply are shown.

Assessing Global Human Exposure to T-2 Toxin via Poultry Meat Consumption Using a Lifetime Physiologically Based Pharmacokinetic Model.

Residue depletion of T-2 toxin in chickens after oral gavage at 2.0 mg/kg twice daily for 2 days was determined in this study. A flow-limited physiologically based pharmacokinetic (PBPK) model was developed for lifetime exposure assessment in chickens. The model was calibrated with data from the residue depletion study and then validated with independent data. A local sensitivity analysis was performed, and 16 sensitive parameters were subjected to Monte Carlo analysis. The population PBPK model was applied to estimate daily intake values of T-2 toxin in different countries based on reported consumption factors and the guidance value of 0.25 mg/kg in feed for chickens by the European Food Safety Authority (EFSA). The predicted daily intakes in different countries were all lower than the EFSA's total daily intake, suggesting that the EFSA's guidance value has minimal risk. This model provides a foundation for scaling to other mycotoxins and other food animal species.

Isoline use in crop composition studies with genetically modified crops under EFSA guidance – Short communication

The European Food Safety Authority (EFSA) oversees the safety evaluation of genetically modified (GM) crops in the European Union. EFSA requires inclusion of commercial non-GM reference lines and a non-GM isoline in crop composition studies with GM crops. Reference lines are used to construct equivalence limits for each compositional analyte. Results for the GM line are compared with these equivalence limits to assess compositional equivalence between the GM crop and the non-GM crop. If compositional equivalence cannot be concluded from this comparison, then results for the non-GM isoline can be used to determine if this finding is likely the result of the background non-GM genetics of the GM crop. If this latter comparison is not sufficient to assess the compositional safety of the GM crop, then a biological-relevance assessment for the analytes in question can be completed taking into account the greater body of knowledge of composition for the crop and diets. Thus, the isoline is a useful comparator but not required to assess the compositional safety of the GM crop, and therefore, unavoidable genotype differences between the isoline and GM line should not be grounds for rejection of compositional studies where the biological relevance of potential non-equivalence is addressed.

Guidelines for reporting 2017 prevalence sample‐based data in accordance with SSD2 data model

Prevalence sample-based data should be transmitted from Member States to the European Food Safety Authority (EFSA) using the EFSA Standard Sample Description version 2 (SSD2) standard. To support reporting countries in data submission using eXtensible Markup Language (XML) data transfer, specific guidelines are given in this report covering the reporting of sample-based zoonoses and zoonotic agent data. These guidelines are specifically aimed at guiding the reporting of information under the framework of Directive 2003/99/EC. The objective is to explain in detail the individual data elements that are included in the EFSA (SSD2) data model to be used for the XML prevalence sample based data transmission through the Data Collection Framework according to the protocol described in the EFSA Guidance on Data Exchange (GDE). In particular the data elements to be reported are explained, including information about the data type, a reference to the list of allowed terms and business rules or requirements that may apply.

Claimed effects, outcome variables and methods of measurement for health claims on foods proposed under Regulation (EC) 1924/2006 in the area of oral health

ObjectiveSome of the requests of authorization to apply health claims in the context of oral health have received a negative scientific opinion from the European Food Safety Authority (EFSA). The main reasons refer to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed at collecting, collating and critically analysing the information in relation to claimed effects, OVs and MMs, in the area of oral health and compliant with Regulation (EC) 1924/2006. MethodsClaimed effects, OVs and the related MMs were collected from EFSA guidance documents and from the scientific opinions on the substantiation of health claims under Articles 13.5 and 14. The collection, collation and critical analysis of the relevant scientific literature consisted in a definition of the keywords, PubMed search strategies and in the creation of databases of references. Results and conclusionsThe critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context each specific claimed effect. Clinical significanceThe information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims related to oral health, as well as to the stakeholders for the identification of existing and design of novel randomized controlled trials aimed at substantiating such health claims.