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EFSA carries out the risk assessment of genetically modified plants for food and feed uses under Regulation (EU) No 503/2013. Exposure assessment – anticipated intake/extend of use shall be an essential element of the risk assessment of genetically modified feeds, as required by Regulation (EU) No 503/2013. Estimates of animal dietary exposure to newly expressed proteins should be determined to cover average consumption across all the different species, age, physiological and productive phases of farmed and companion animals, and identify and consider particular consumer groups with expected higher exposure. This statement is aimed at facilitating the reporting of the information that applicants need to provide on expected animal dietary exposure to newly expressed proteins and to increase harmonisation of the application dossiers to be assessed by the EFSA GMO Panel. Advice is provided on the selection of proper feed consumption and feed concentration data, and on the reporting of exposure's estimates. An overview of the different uncertainties that may be linked to the estimations is provided. This statement also explains how to access an Excel calculator which should be used in future applications as basis to provide a more consistent presentation of estimates of expected animal dietary exposure.

The European Commission requested the Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA GMO Panel) to assess new scientific information on maize MIR162, and to indicate whether the previous conclusions on the safety of maize MIR162 as a single event and as a part of stacked events remain valid. The new information is included in a European patent that reports a decrease in male fertility in some MIR162 inbred lines, pointing to a potential link between such decrease and the Vip3 protein expressed by maize MIR162. The EFSA GMO Panel evaluated the data provided by the patent owner and found scarce support for a causal link between Vip3 and decreased fertility. The general hypothesis of an association between event MIR162 and altered fertility could not be confirmed. The EFSA GMO Panel conducted the safety assessment based on the conservative assumption that such an association exists. The EFSA GMO Panel concluded that a decrease in male fertility would have no impact on the previous conclusions on maize MIR162 and stacked events containing MIR162.

Following the submission of application EFSA-GMO-RX-024 under Regulation (EC) No 1829/2003 from BASF Agricultural Solutions Seed US LLC, the Panel on Genetically Modified Organisms of EFSA was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide tolerant genetically modified oilseed rape MS8, RF3 and MS8 × RF3, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in oilseed rape MS8, RF3 and MS8 × RF3 considered for renewal are identical to the sequences of the originally assessed events, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-024 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on oilseed rape MS8, RF3 and MS8 × RF3.

Genetically modified maize MON 87419 was developed to confer tolerance to dicamba- and glufosinate-based herbicides. These properties were achieved by introducing the dmo and pat expression cassettes. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize MON 87419 and its conventional counterpart needed further assessment, except for the levels of arginine and protein in grains which did not raise safety and nutritional concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the dicamba mono-oxygenase (DMO) and phosphinothricin N-acetyltransferase (PAT) proteins as expressed in maize MON 87419. The GMO Panel finds no evidence that the genetic modification impacts the overall safety of maize MON 87419. In the context of this application, the consumption of food and feed from maize MON 87419 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize MON 87419 is as safe as the conventional counterpart and non-GM maize varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable maize MON 87419 grains into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize MON 87419. The GMO Panel concludes that maize MON 87419 is as safe as its conventional counterpart and the tested non-GM maize varieties with respect to potential effects on human and animal health and the environment.

Genetically modified maize Bt11 × MIR162 × MIR604 × MON 89034 × 5307 × GA21 was developed by crossing to combine six single events: Bt11, MIR162, MIR604, MON 89034, 5307 and GA21, the GMO Panel previously assessed the 6 single maize events and 27 out of the 56 possible subcombinations and did not identify safety concerns. No new data on the single maize events or the assessed subcombinations were identified that could lead to modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in the six-event stack maize does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that six-event stack maize, as described in this application, is as safe as the conventional counterpart and non-GM maize varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable six-event stack maize grains into the environment, this would not raise environmental safety concerns. The GMO Panel assessed the likelihood of interactions among the single events in 29 of the maize subcombinations not previously assessed and covered by the scope of this application and concludes that these are expected to be as safe as the single events, the previously assessed subcombinations and the six-event stack maize. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize Bt11 × MIR162 × MIR604 × MON 89034 × 5307 × GA21. The GMO Panel concludes that six-event stack maize and the 30 subcombinations covered by the scope of the application are as safe as its conventional counterpart and the tested non-GM maize varieties with respect to potential effects on human and animal health

Genetically modified maize GA21 × T25 was developed by crossing to combine two single events: GA21 and T25. The GMO Panel previously assessed the two single maize events and did not identify safety concerns. No new data on the single maize events were identified that could lead to modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in maize GA21 × T25 does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that maize GA21 × T25, as described in this application, is as safe as its conventional counterpart and the non-GM reference varieties tested, and no post-market monitoring of food and feed is considered necessary. In the case of accidental release of viable maize GA21 × T25 grains into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize GA21 × T25. Post-market monitoring of food and feed is not considered necessary. The GMO Panel concludes that maize GA21 × T25 is as safe as its conventional counterpart and the non-GM reference varieties tested, with respect to potential effects on human and animal health and the environment.

Genetically modified cotton COT102 was developed to confer resistance against several lepidopteran species. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the differences in the agronomic-phenotypic and compositional characteristics between cotton COT102 and its non-GM comparator needs further assessment, except for levels of acid detergent fibre, which do not raise safety or nutritional concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the Vip3Aa19 and APH4 proteins as expressed in cotton COT102 and finds no evidence that the genetic modification would change the overall allergenicity of cotton COT102. In the context of this application, the consumption of food and feed from cotton COT102 does not represent a nutritional concern for humans and animals. The GMO Panel concludes that cotton COT102 is as safe as the non-GM comparator and non-GM cotton varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable cotton COT102 seeds into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of cotton COT102. The GMO Panel concludes that cotton COT102 is as safe as its non-GM comparator and the tested non-GM cotton varieties with respect to potential effects on human and animal health and the environment.

Genetically modified (GM) soybean 40-3-2 expresses a 5-enolpyruvylshikimate-3-phosphate synthase protein from Agrobacterium sp. strain CP4 (CP4 EPSPS), which confers tolerance to glyphosate. This event was previously assessed by the GMO Panel as a single event and as part of a two-event stack and was found to be as safe as its conventional counterparts and other appropriate comparators with respect to potential effects on human and animal health and the environment. On September 2021, the European Commission requested EFSA to evaluate a new bioinformatics study which revealed predicted genomic deletions at the insertion sites using the available soybean reference genome. Considering the variability of the soybean genome, with a number of structural variants such as presence/absence variants and copy number variants including genic regions, as well as the fact that a number of genes are present only in particular varieties, the GMO Panel concludes that comparing only to the reference genome does not allow to conclude that the transformation event resulted in gene loss. In support of this, the transcriptomic analysis did not show major differences in gene expression when comparing the soybean 40-3-2 with the most closely related conventional variety, indicating that the genetic redundancy may compensate for the potential gene loss. Moreover, the composition, phenotypic and agronomic analyses already assessed by the GMO Panel in previous opinions did not show differences between soybean 40-3-2 and its comparators suggesting that the potential gene loss may not have a significant phenotypic effect in soybean 40-3-2. For these reasons, the EFSA GMO Panel concludes that the new information provided by the applicant on soybean 40-3-2 does not alter EFSA's previous conclusions.

This Scientific Opinion addresses the formulation of specific development needs, including research requirements for allergenicity assessment and protein safety, in general, which is urgently needed in a world that demands more sustainable food systems. Current allergenicity risk assessment strategies are based on the principles and guidelines of the Codex Alimentarius for the safety assessment of foods derived from ‘modern’ biotechnology initially published in 2003. The core approach for the safety assessment is based on a ‘weight-of-evidence’ approach because no single piece of information or experimental method provides sufficient evidence to predict allergenicity. Although the Codex Alimentarius and EFSA guidance documents successfully addressed allergenicity assessments of single/stacked event GM applications, experience gained and new developments in the field call for a modernisation of some key elements of the risk assessment. These should include the consideration of clinical relevance, route of exposure and potential threshold values of food allergens, the update of in silico tools used with more targeted databases and better integration and standardisation of test materials and in vitro/in vivo protocols. Furthermore, more complex future products will likely challenge the overall practical implementation of current guidelines, which were mainly targeted to assess a few newly expressed proteins. Therefore, it is timely to review and clarify the main purpose of the allergenicity risk assessment and the vital role it plays in protecting consumers' health. A roadmap to (re)define the allergenicity safety objectives and risk assessment needs will be required to inform a series of key questions for risk assessors and risk managers such as ‘what is the purpose of the allergenicity risk assessment?’ or ‘what level of confidence is necessary for the predictions?’.

In a previous scientific opinion on application EFSA-GMO-BE-2016-138, the EFSA Panel on Genetically Modified Organisms (GMO Panel) could not conclude on the comparative analysis and on the food/feed safety assessment of genetically modified (GM) oilseed rape (OSR) MS11 because of the lack of an appropriate compositional data set. Following a request from the European Commission, the GMO Panel assessed additional information related to OSR MS11 to complement the original scientific opinion. The GMO Panel concluded that the information submitted (on the composition of the two-event stack MS11 × RF3) could not be used for the assessment of the composition of OSR MS11 and requested the applicant to perform a complementary set of field trials to generate additional data. The applicant did not perform the requested field trials and did not provide any new experimental data on the composition of OSR MS11. Hence, the GMO Panel is still not in the position to conclude on either the compositional analysis or the toxicological, allergenicity or nutritional assessment of OSR MS11. Therefore, the previous conclusions of the GMO Panel still hold.

In 2012, EFSA issued an opinion on plants developed through cisgenesis and intragenesis. With the development of New Genomic Techniques (NGTs) in the last decade, cisgenic and intragenic plants can now be obtained with the insertion of a desired sequence in a precise location of the genome. EFSA has been requested by European Commission to provide an updated scientific opinion on the safety and the risk assessment of plants developed through cisgenesis and intragenesis, in order to (i) identify potential risks, comparing them with those posed by plants obtained by conventional breeding and Established Genomic Techniques (EGTs) and (ii) to determine the applicability of current guidelines for the risk assessment of cisgenic and intragenic plants. The conclusions of the previous EFSA opinion were reviewed, taking into consideration the new guidelines and the recent literature. The GMO panel concludes that no new risks are identified in cisgenic and intragenic plants obtained with NGTs, as compared with those already considered for plants obtained with conventional breeding and EGTs. There are no new data since the publication of the 2012 EFSA opinion that would challenge the conclusions raised in that document. The conclusions of the EFSA 2012 Scientific Opinion remain valid. The EFSA GMO Panel reiterates from these conclusions that with respect to the source of DNA and the safety of the gene product, the hazards arising from the use of a related plant-derived gene by cisgenesis are similar to those from conventional plant breeding, whereas additional hazards may arise for intragenic plants. Furthermore, the EFSA GMO Panel considers that cisgenesis and intragenesis make use of the same transformation techniques as transgenesis, and therefore, with respect to the alterations to the host genome, cisgenic, intragenic and transgenic plants obtained by random insertion do not cause different hazards. Compared to that, the use of NGTs reduces the risks associated with poten

Synthetic biology (SynBio) is an interdisciplinary field at the interface of molecular engineering and biology aiming to develop new biological systems and impart new functions to living cells, tissues and organisms. EFSA has been asked by the European Commission to evaluate SynBio developments in agri-food with the aim of identifying the adequacy and sufficiency of existing guidelines for risk assessment and determine if updated guidance is needed. In this context, the GMO Panel has previously adopted an Opinion evaluating the SynBio developments in agri-food/feed and the adequacy and sufficiency of existing guidelines for the molecular characterisation and environmental risk assessment of genetically modified plants (GMPs) obtained through SynBio and reaching the market in the next decade. Complementing the above, in this Opinion, the GMO Panel evaluated the adequacy and sufficiency of existing guidelines for the food and feed risk assessment of GMPs obtained through SynBio. Using selected hypothetical case studies, the GMO Panel did not identify novel potential hazards and risks that could be posed by food and feed from GMPs obtained through current and near future SynBio approaches; considers that the existing guidelines are adequate and sufficient in some Synbio applications; in other cases, existing guidelines may be just adequate and hence need updating; areas needing updating include those related to the safety assessment of new proteins and the comparative analysis. The GMO Panel recommends that future guidance documents provide indications on how to integrate the knowledge available from the SynBio design and modelling in the food and feed risk assessment and encourages due consideration to be given to food and feed safety aspects throughout the SynBio design process as a way to facilitate the risk assessment of SynBio GMPs and reduce the amount of data required.

EFSA was asked by the european Commission to develop criteria as advice for consideration for the risk assessment of plants produced by targeted mutagenesis, cisgenesis and intragenesis. EFSA proposes in this statement six main criteria to assist the risk assessment of these plants. The first four criteria are related to the molecular characterisation of the genetic modification introduced in the recipient plant. The four criteria evaluate whether any exogenous DNA sequence(s) is/are present (Criterion 1), whether such sequence derives from the breeders' gene pool (Criterion 2), the type of integration (Criterion 3) and whether any endogenous plant gene is interrupted (Criterion 4). Depending on the evaluation of the above criteria, the product can be a genome edited plant where no exogenous DNA sequence is present, or a cisgenic or intragenic plant where the cisgenic and intragenic sequence are introduced by targeted insertion and no plant endogenous genes are interrupted. In these cases, two more criteria are assessed to evaluate the history of safe use (Criterion 5) and the structure and function of the new allele (Criterion 6). If cisgenic and intragenic sequence are introduced by random integration without interruption of an endogenous gene, or when no risk is identified when an endogenous gene is interrupted, the criteria 5 and 6 will also be assessed. Evaluating the history of safe use is an important part of the proportionate risk assessment of cisgenic, intragenic and genome-edited plants since the newly introduced allele may already be present in nature. However, when the history of safe use cannot be sufficiently demonstrated, the function and structure of the introduced allele should be carefully assessed. Recommendations are also included on the aspects that need further elaboration for full applicability of the criteria proposed herein are also included.

Maize MON 87429 was developed to confer tolerance to dicamba, glufosinate, quizalofop and 2,4-D herbicides. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between maize MON 87429 and its conventional counterpart needs further assessment, except for the levels of phytic acid in grains, which do not raise nutritional and safety concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the DMO, PAT, FT_T and CP4 EPSPS proteins as expressed in maize MON 87429. The GMO Panel finds no evidence that the genetic modification impacts the overall safety of maize MON 87429. In the context of this application, the consumption of food and feed from maize MON 87429 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that maize MON 87429 is as safe as the conventional counterpart and non-GM maize reference varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable maize MON 87429 grains into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize MON 87429. The GMO Panel concludes that maize MON 87429, as described in this application, is as safe as its conventional counterpart and the tested non-GM maize reference varieties with respect to potential effects on human and animal health and the environment.

Genetically modified maize MON 89034 × 1507 × MIR162 × NK603 × DAS-40278-9 was developed by crossing to combine five single events: MON 89034, 1507, MIR162, NK603 and DAS-40278-9. The GMO Panel previously assessed the five single maize events and 16 of the subcombinations and did not identify safety concerns. No new data on the single maize events or the assessed subcombinations were identified that could lead to the modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in the five-event stack maize does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that five-event stack maize, as described in this application, is as safe as the non-GM comparator and non-GM maize varieties tested. In the case of accidental release of viable five-event stack maize grains into the environment, this would not raise environmental safety concerns. The GMO Panel assessed the likelihood of interactions among the single events in nine of the maize subcombinations not previously assessed and concludes that these are expected to be as safe as the single events, the previously assessed subcombinations and the five-event stack maize. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize MON 89034 × 1507 × MIR162 × NK603 × DAS-40278-9. Post-market monitoring of food/feed is not considered necessary. The GMO Panel concludes that the five-event stack maize and its subcombinations are as safe as its non-GM comparator and the tested non-GM maize varieties with respect to potential effects on human and animal health and the environment.

Following the submission of application EFSA-GMO-RX-026/1 under Regulation (EC) No 1829/2003 from Bayer Agriculture BV on behalf of Bayer CropScience LP, the Panel on Genetically Modified Organisms of EFSA was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for foods and food ingredients containing, consisting of, or produced from oilseed rape GT73 with the exception of isolated seed protein, and feed produced from this GM oilseed rape, excluding cultivation in the EU. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and a search for additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in oilseed rape GT73 considered for renewal are identical to the sequences of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-026/1 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on oilseed rape GT73.

Following the submission of application EFSA-GMO-RX-022 under Regulation (EC) No 1829/2003 from Bayer CropScience LP, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect-resistant and herbicide-tolerant genetically modified soybean MON 87701 × MON 89788, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in soybean MON 87701 × MON 89788 considered for renewal are identical to the sequences of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-022 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on soybean MON 87701 × MON 89788.

DAS-21Ø23-5 and concluded that it is as safe as its conventional counterpart and other appropriate comparators with respect to potential effects on human and animal health and the environment in the context of its intended uses. On 17 November 2020, the European Commission requested EFSA to evaluate new DNA sequence information and updated bioinformatics data for cotton DAS-24236-5 × DAS-21Ø23-5 and to indicate whether the conclusions of the GMO Panel on the previously assessed cotton DAS-24236-5 × DAS-21Ø23-5 remain valid. The new sequence data of DAS-24236-5 showed the change of one nucleotide that results in one amino acid substitution, in the newly expressed Cry1F (synpro_L620Q) compared to the sequence originally reported. The GMO Panel concludes that this amino acid substitution in the protein is a mutation. Nonetheless with the exception of the bioinformatics analysis, the studies performed for the risk assessment of Cry1F in cotton DAS-24236-5 × DAS-21Ø23-5 remain valid. In addition, the new sequencing data showed a change in one nucleotide in the 5′ flanking region of DAS-21Ø23-5 compared to the original sequence reported on the stack cotton DAS-24236-5 × DAS-21Ø23-5. The bioinformatic analyses of the newly sequenced DAS-21Ø23-5 event in the stack DAS-24236-5 × DAS-21Ø23-5 shows that the nucleotide difference is in the 5′ flanking region outside the ORFs that span the 5′ junction and is therefore not considered further in the safety assessment. Based on the information provided, the GMO Panel concludes that the corrected sequence does not give rise to any safety concerns, and therefore, the original risk assessment of cotton DAS-24236-5 × DAS-21Ø23-5 remains valid.

Maize DP4114 × MON 810 × MIR604 × NK603 (four-event stack maize) was produced by conventional crossing to combine four single events: DP4114, MON 810, MIR604 and NK603. The GMO Panel previously assessed the four single maize events and one of the subcombinations and did not identify safety concerns. No new data on the single maize events or the assessed subcombination were identified that could lead to modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in the four-event stack maize does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that the four-event stack maize, is as safe as the comparator and the selected non-GM reference varieties. In the case of accidental release of viable grains of the four-event stack maize into the environment, this would not raise environmental safety concerns. The GMO Panel assessed the likelihood of interactions among the single events in nine of the maize subcombinations not previously assessed and concludes that these are expected to be as safe as the single events, the previously assessed subcombination and the four-event stack maize. Post-market monitoring of food/feed is not considered necessary. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of the four-event stack maize. The GMO Panel concludes that the four-event stack maize and its subcombinations are as safe as the non-GM comparator and the selected non-GM reference varieties with respect to potential effects on human and animal health and the environment.

Following the submission of application EFSA–GMO–RX–018 under Regulation (EC) No 1829/2003 from BASF Agricultural Solutions Seed US LLC, the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide-tolerant genetically modified cotton GHB614, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. The GMO Panel concludes that there is no evidence in renewal application EFSA–GMO–RX–018 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on cotton GHB614.

Cotton GHB811 was developed to confer tolerance to glyphosate and HPPD inhibitor herbicides. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between cotton GHB811 and its conventional counterpart needs further assessment, except for % lint, lint length and dihydrosterculic acid, which do not raise nutritional and safety concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the 2mEPSPS and HPPD W336 proteins as expressed in cotton GHB811 and finds no evidence that the genetic modification would change the overall allergenicity of cotton GHB811. In the context of this application, the consumption of food and feed from cotton GHB811 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that cotton GHB811 is as safe as the conventional counterpart and non-GM cotton reference varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable cotton GHB811 seeds into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of cotton GHB811. The GMO Panel concludes that cotton GHB811 is as safe as its conventional counterpart and the tested non-GM cotton reference varieties with respect to potential effects on human and animal health and the environment.

Following the submission of application EFSA-GMO-RX-017 under Regulation (EC) No 1829/2003 from Bayer Agriculture BVBA the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect-resistant and herbicide-tolerant genetically modified maize MON 88017 × MON 810, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, and updated bioinformatic analysis. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the events in maize MON 88017 × MON 810 considered for renewal are identical to the sequence of the originally assessed events, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-017 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize MON 88017 × MON 810.

Oilseed rape 73496 was developed to confer tolerance to the herbicidal active substance glyphosate through the expression of the glyphosate acetyltransferase protein GAT4621. The molecular characterisation data and bioinformatic analyses identify no issues requiring food/feed safety assessment. None of the identified differences between oilseed rape 73496 and its conventional counterpart in the agronomic/phenotypic endpoints tested needs further assessment. Differences identified in seed composition of oilseed rape 73496 as compared to its conventional counterpart raise no safety and nutritional concerns in the context of the scope of this application. No safety concerns are identified regarding toxicity and allergenicity of the GAT4621 protein as expressed in oilseed rape 73496. No evidence is found that the genetic modification would change the overall allergenicity of oilseed rape 73496. Based on the outcome of the comparative and nutritional assessments, the consumption of oilseed rape 73496 does not represent any nutritional concern, in the context of the scope of this application. The implementation of a post-market monitoring plan is recommended to confirm the predicted consumption data and to verify that the conditions of use are those considered during the pre-market risk assessment. In the case of accidental release of viable oilseed rape 73496 seeds into the environment, oilseed rape 73496 would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of oilseed rape 73496. The GMO Panel concludes that oilseed rape 73496, as described in this application, is as safe as its conventional counterpart and the non-genetically modified oilseed rape reference varieties tested with respect to potential effects on human and animal health and the environment.

This statement supplements and updates the GMO Panel guidance document on allergenicity of genetically modified (GM) plants published in 2017. In that guidance document, the GMO Panel considered that additional investigations on in vitro protein digestibility were needed before providing any additional recommendations in the form of guidance to applicants. Thus, an interim phase was proposed to assess the utility of an enhanced in vitro digestion test, as compared to the classical pepsin resistance test. Historically, resistance to degradation by pepsin using the classical pepsin resistance test has been considered as additional information, in a weight-of-evidence approach, for the assessment of allergenicity and toxicity of newly expressed proteins in GM plants. However, more recent evidence does not support this test as a good predictor of allergenic potential for hazard. Furthermore, there is a need for more reliable systems to predict the fate of the proteins in the gastrointestinal tract and how they interact with the relevant human cells. Nevertheless, the classical pepsin resistance test can still provide some information on the physicochemical properties of novel proteins relating to their stability under acidic conditions. But other methods can be used to obtain data on protein's structural and/or functional integrity. It is acknowledged that the classical pepsin resistance test is embedded into international guidelines, e.g. Codex Alimentarius and Regulation (EU) No 503/2013. For future development, a deeper understanding of protein digestion in the gastrointestinal tract could enable the framing of more robust strategies for the safety assessment of proteins. Given the high complexity of the digestion and absorption process of dietary proteins, it is needed to clarify and identify the aspects that could be relevant to assess potential risks of allergenicity and toxicity of proteins. To this end, a series of research questions to be addressed are also for

Mutations are changes in the genetic material that may be transmitted to subsequent generations. Mutations appear spontaneously in nature and are one of the underlying driving forces of evolution. In plants, in vivo and in vitro random mutagenesis relies on the application of physical and chemical mutagens to increase the frequency of mutations thus accelerating the selection of varieties with important agronomic traits. The European Commission has requested EFSA to provide a more detailed description of in vivo and in vitro random mutagenesis techniques and the types of mutations and mechanisms involved, to be able to conclude on whether in vivo and in vitro random mutagenesis techniques are to be considered different techniques. To address the European Commission request, a literature search was conducted to collect information on the random mutagenesis techniques used in plants both in vivo and in vitro, on the type of mutations generated by such techniques and on the molecular mechanisms underlying formation of those mutations. The GMO Panel concludes that most physical and chemical mutagenesis techniques have been applied both in vivo and in vitro; the mutation process and the repair mechanisms act at cellular level and thus there is no difference between application of the mutagen in vivo or in vitro; and the type of mutations induced by a specific mutagen are expected to be the same, regardless of whether such mutagen is applied in vivo or in vitro. Indeed, the same mutation and the derived trait in a given plant species can be potentially obtained using both in vivo and in vitro random mutagenesis and the resulting mutants would be indistinguishable. Therefore, the GMO Panel concludes that the distinction between plants obtained by in vitro or in vivo approaches is not justified.

Synthetic Biology (SynBio) is an interdisciplinary field at the interface of engineering and biology aiming to develop new biological systems and impart new functions to living cells. EFSA has been asked by the European Commission to evaluate SynBio developments in agri-food with the aim of identifying the adequacy of existing guidelines for risk assessment and determine if updated guidance is needed. The scope of this opinion covers the molecular characterisation and environmental risk assessment of such genetically modified plants obtained through SynBio, meant to be for cultivation or food and feed purposes. The previous work on SynBio by the non-food scientific Committees (2014, 2015) was used and complemented with the output of a horizon scanning exercise, which was commissioned by the EFSA to identify the most realistic and forthcoming SynBio cases of relevance to this remit. The horizon scan did not identify other sectors/advances in addition to the six SynBio categories previously identified by the non-food scientific committees of the European Commission. The exercise did show that plant SynBio products reaching the market in the near future (next decade) are likely to apply SynBio approaches to their development using existing genetic modification and genome editing technologies. In addition, three hypothetical SynBio case studies were selected by the working group of the Panel on Genetically Modified Organisms (GMO), to further support the scoping exercise of this Scientific Opinion. Using the selected cases, the GMO Panel concludes that the requirements of the EU regulatory framework and existing EFSA guidelines are adequate for the risk assessment of SynBio products to be developed in the next 10 years, although specific requirements may not apply to all products. The GMO Panel acknowledges that as SynBio developments evolve, a need may exist to adjust the guidelines to ensure they are adequate and sufficient.

Maize NK603 × T25 × DAS-40278-9 (three-event stack maize) was produced by conventional crossing to combine three single events: NK603, T25 and DAS-40278-9. The GMO Panel previously assessed the three single maize events and two of the subcombinations and did not identify safety concerns. No new data on the single maize events or the two subcombinations were identified that could lead to modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in the three-event stack maize does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that the three-event stack maize, as described in this application, is as safe as the non-GM comparator and the selected non-GM reference varieties. In the case of accidental release of viable grains of the three-event stack maize into the environment, this would not raise environmental safety concerns. The GMO Panel assessed the likelihood of interactions among the single events in one of the maize subcombinations not previously assessed and concludes that these are expected to be as safe as the single events, the previously assessed subcombinations and the three-event stack maize. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of the three-event stack maize. Post-market monitoring of food/feed is not considered necessary. The GMO Panel concludes that the three-event stack maize and its subcombinations are as safe as the non-GM comparator and the selected non-GM reference varieties with respect to potential effects on human and animal health and the environment.

Maize 1507 × MIR162 × MON810 × NK603 (four-event stack maize) was produced by conventional crossing to combine four single events: 1507, MIR162, MON810 and NK603. The GMO Panel previously assessed the four single events and six of the subcombinations and did not identify safety concerns. No new data on the single events or the six subcombinations that could lead to modification of the original conclusions on their safety were identified. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins in the four-event stack maize does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that the four-event stack maize, as described in this application, is as safe as its non-GM comparator and the non-GM reference varieties tested. In the case of accidental release of viable seeds of the four-event stack maize into the environment, this would not raise environmental safety concerns. The GMO Panel assessed the likelihood of interactions among the single events in the four maize subcombinations not previously assessed and concludes that these are expected to be as safe as the single events, the previously assessed subcombinations and the four-event stack maize. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of the four-event stack maize. Post-market monitoring of food/feed is not considered necessary. The GMO Panel concludes that the four-event stack maize and its subcombinations are as safe as the non-GM comparator and the tested non-GM reference varieties with respect to potential effects on human and animal health and the environment.

Soybean GMB151 was developed to confer tolerance to 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicides and resistance to nematodes. The molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic and compositional characteristics tested between soybean GMB151 and its conventional counterpart needs further assessment, except for palmitic acid and heptadecenoic acid in seeds and carbohydrate and crude protein in forage, which does not raise nutritional and safety concerns. The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of the HPPD-4 and Cry14Ab-1 proteins as expressed in soybean GMB151, and finds no evidence that the genetic modification would change the overall allergenicity of soybean GMB151. In the context of this application, the consumption of food and feed from soybean GMB151 does not represent a nutritional concern in humans and animals. The GMO Panel concludes that soybean GMB151 is as safe as the conventional counterpart and non-GM soybean reference varieties tested, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable soybean GMB151 seeds into the environment, this would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of soybean GMB151. The GMO Panel concludes that soybean GMB151 is as safe as its conventional counterpart and the tested non-GM soybean reference varieties with respect to potential effects on human and animal health and the environment.

Maize MON 87427 × MON 87460 × MON 89034 × 1507 × MON 87411 × 59122 (six-event stack maize) was produced by conventional crossing to combine six single events: MON 87427, MON 87460, MON 89034, 1507, MON 87411 and 59122. The GMO Panel previously assessed the six single maize events and 17 of the subcombinations and did not identify safety concerns. No new data on the single maize events or the 17 subcombinations were identified that could lead to modification of the original conclusions on their safety. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single maize events and of the newly expressed proteins and dsRNA in the six-event stack maize does not give rise to food and feed safety and nutritional concerns. The GMO Panel concludes that the six-event stack maize, as described in this application, is as safe as its non-GM comparator and the selected non-GM reference varieties. In the case of accidental release of viable grains of the six-event stack maize into the environment, this would not raise environmental safety concerns. The GMO Panel assessed the likelihood of interactions among the single events in the 39 maize subcombinations not previously assessed and concludes that these are expected to be as safe as the single events, the previously assessed subcombinations and the six–event stack maize. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of the six-event stack maize. Post-market monitoring of food/feed is not considered necessary. The GMO Panel concludes that the six-event stack maize and its subcombinations are as safe as the non-GM comparator and the selected non-GM reference varieties with respect to potential effects on human and animal health and the environment.

Following the submission of application EFSA-GMO-RX-016 under Regulation (EC) No 1829/2003 from Syngenta the Panel on Genetically Modified Organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the insect-resistant and herbicide-tolerant genetically modified maize Bt11, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatic analyses, and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequences of the event in maize Bt11 considered for renewal is identical to the sequence of the originally assessed events, the GMO Panel concludes that there is no evidence in renewal application EFSA-GMO-RX-016 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize Bt11.

Soybean DAS–8419–2 × DAS–44406–6 was developed to provide protection against certain lepidopteran pests and tolerance to 2,4–dichlorophenoxyacetic acid and other related phenoxy herbicides, and glyphosate‐ and glufosinate ammonium‐containing herbicides. The Genetically Modified Organisms (GMO) Panel previously assessed the two single soybean events and did not identify safety concerns. No new data on the single soybean events, leading to modification of the original conclusions on their safety have been identified. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single soybean events and of the newly expressed proteins in the two‐event stack soybean does not give rise to food and feed safety and nutritional concerns. In the case of accidental release of viable DAS–8419–2 × DAS–44406–6 seeds into the environment, soybean DAS–8419–2 × DAS–44406–6 would not raise environmental safety concerns. The post‐market environmental monitoring plan and reporting intervals are in line with the intended uses of soybean DAS–8419–2 × DAS–44406–6. In conclusion, the GMO Panel considers that soybean DAS–8419–2 × DAS–44406–6, as described in this application, is as safe as its conventional counterpart and the non‐genetically modified soybean reference varieties tested with respect to potential effects on human and animal health and the environment.

The EFSA Panel on Genetically Modified Organisms (GMO) previously assessed oilseed rape Ms8 × Rf3 × GT73 and its subcombinations Ms8 × GT73 and Rf3 × GT73 according to the scope as defined in the application EFSA¿GMO¿NL¿2009¿75, and was not in the position to complete the safety assessment of products rich in protein, such as rapeseed protein isolates or products of this nature in animal feeding. Following a mandate from the European Commission, the GMO Panel assessed a 28¿day toxicity study in mice with the glyphosate oxidoreductase (GOXv247) protein, provided to complement information related to application EFSA¿GMO¿NL¿2009¿75 for the placing on the market of oilseed rape Ms8 × Rf3 × GT73 and its subcombinations Ms8 × GT73 and Rf3 × GT73, for food and feed uses, import and processing, with the exception of isolated seed protein for food. The 28¿day toxicity study on Escherichia coli¿ produced GOXv247 protein did not show adverse effects in mice, at the gavage doses up to 1000 mg/kg body weight (bw) per day. Taking into account its previous assessment on EFSA¿GMO¿NL¿2009¿75 and the outcome of the 28¿day toxicity study in mice with the GOXv247 protein provided in this mandate, the GMO Panel, based on a weight of evidence approach, concludes that food and feed containing, consisting and produced from genetically modified oilseed rape Ms8 × Rf3 × GT73 and its sub combinations Ms8 × GT73 and Rf3 × GT73, are as safe as its conventional counterpart, according to the scope as defined in the application EFSA¿GMO¿NL¿2009¿75.

Oilseed rape MS11 has been developed to confer male sterility and tolerance to glufosinate‐ammonium‐containing herbicides. Based on the information provided in the application and in line with the scope of application EFSA‐GMO‐BE‐2016‐138, the genetically modified organism (GMO) Panel concludes that the molecular characterisation data and bioinformatic analyses do not identify issues requiring food/feed safety assessment. None of the identified differences in the agronomic/phenotypic characteristics tested between oilseed rape MS11 and its conventional counterpart needs further assessment. No conclusions can be drawn for the compositional analysis due to the lack of an appropriate compositional data set. No toxicological or allergenicity concerns are identified for the Barnase, Barstar and PAT/bar proteins expressed in oilseed rape MS11. Owing to the incompleteness of the compositional analysis, the toxicological, allergenicity and nutritional assessment of oilseed rape MS11 cannot be completed. In the case of accidental release of viable oilseed rape MS11 seeds into the environment, oilseed rape MS11 would not raise environmental safety concerns. The post‐market environmental monitoring plan and reporting intervals are in line with the scope of the application. Since oilseed rape MS11 is designed to be used only for the production of hybrid seed, it is not expected to be commercialised as a stand‐alone product for food/feed uses. Thus, seeds harvested from oilseed rape MS11 are not expected to enter the food/feed chain, except accidentally. In this context, the GMO Panel notes that, oilseed rape MS11 would not pose risk to humans and animals, while the scale of environmental exposure will be substantially reduced compared to a stand‐alone product.

Soybean MON 87705 × MON 87708 × MON 89788 (three‐event stack soybean) was produced by conventional crossing to combine three single soybean events: MON 87705, MON 87708 and MON 89788. This combination is intended to alter the fatty acid profile in the seed (in particular increasing the levels of oleic acid) and tolerance to glyphosate‐based and dicamba herbicides. The Genetically Modified Organisms Panel previously assessed the three single soybean events and did not identify safety concerns. No new data on the single soybean events, leading to modification of the original conclusions on their safety have been identified. The molecular characterisation, comparative analysis (agronomic, phenotypic and compositional characteristics) and the outcome of the toxicological, allergenicity and nutritional assessment indicate that the combination of the single soybean events and of the newly expressed proteins in the three‐event stack soybean does not give rise to food and feed safety and nutritional concerns. In the case of accidental release of viable three‐event stack soybean seeds into the environment, this would not raise environmental safety concerns. The post‐market environmental monitoring plan and the reporting intervals are in line with the intended uses of soybean MON 87705 × MON 87708 × MON 89788. Considering the altered fatty acid profile of the three‐event stack soybean, a proposal for post‐market monitoring needs to be provided by the applicant. The GMO Panel notes that in the context of this application EFSA‐GMO‐NL‐2015‐126 the applicant did not provide a 90‐day study on MON 87705 soybean in line with the applicable legal requirements. Therefore, the GMO Panel is not in the position to finalise the risk assessment of soybean MON 87705 × MON 87708 × MON 89788 under the current regulatory frame.