Humoral and cellular immune response in Wistar Han RCC rats fed two genetically modified maize MON810 varieties for 90 days (EU 7th Framework Programme project GRACE).

The genetically modified maize event MON810 expresses a Bacillus thuringiensis-derived gene, which encodes the insecticidal protein Cry1Ab to control some lepidopteran insect pests such as the European corn borer. It has been claimed that the immune system may be affected following the oral/intragastric administration of the MON810 maize in various different animal species. In the frame of the EU-funded project GRACE, two 90-day feeding trials, the so-called studies D and E, were performed to analyze the humoral and cellular immune responses of male and female Wistar Han RCC rats fed the MON810 maize. A MON810 maize variety of Monsanto was used in the study D and a MON810 maize variety of Pioneer Hi-Bred was used in the study E. The total as well as the maize protein- and Cry1Ab-serum-specific IgG, IgM, IgA and IgE levels, the proliferative activity of the lymphocytes, the phagocytic activity of the granulocytes and monocytes, the respiratory burst of the phagocytes, a phenotypic analysis of spleen, thymus and lymph node cells as well as the in vitro production of cytokines by spleen cells were analyzed. No specific Cry1Ab immune response was observed in MON810 rats, and anti-maize protein antibody responses were similar in MON810 and control rats. Single parameters were sporadically altered in rats fed the MON810 maize when compared to control rats, but these alterations are considered to be of no immunotoxicological significance.

Exposure of livestock to GM feeds: Detectability and measurement.

This review explores the possibilities to determine livestock consumption of genetically modified (GM) feeds/ingredients including detection of genetically modified organism (GMO)-related DNA or proteins in animal samples, and the documentary system that is in place for GM feeds under EU legislation. The presence and level of GMO-related DNA and proteins can generally be readily measured in feeds, using established analytical methods such as polymerase chain reaction and immuno-assays, respectively. Various technical challenges remain, such as the simultaneous detection of multiple GMOs and the identification of unauthorized GMOs for which incomplete data on the inserted DNA may exist. Given that transfer of specific GMO-related DNA or protein from consumed feed to the animal had seldom been observed, this cannot serve as an indicator of the individual animal's prior exposure to GM feeds. To explore whether common practices, information exchange and the specific GM feed traceability system in the EU would allow to record GM feed consumption, the dairy chain in Catalonia, where GM maize is widely grown, was taken as an example. It was thus found that this system would neither enable determination of an animal's consumption of specific GM crops, nor would it allow for quantitation of the exposure.

Case studies on genetically modified organisms (GMOs): Potential risk scenarios and associated health indicators.

Within the frame of the EU-funded MARLON project, background data were reviewed to explore the possibility of measuring health indicators during post-market monitoring for potential effects of feeds, particularly genetically modified (GM) feeds, on livestock animal health, if applicable. Four case studies (CSs) of potential health effects on livestock were framed and the current knowledge of a possible effect of GM feed was reviewed. Concerning allergenicity (CS-1), there are no case-reports of allergic reactions or immunotoxic effects resulting from GM feed consumption as compared with non-GM feed. The likelihood of horizontal gene transfer (HGT; CS-2) of GMO-related DNA to different species is not different from that for other DNA and is unlikely to raise health concerns. Concerning mycotoxins (CS-3), insect-resistant GM maize may reduce fumonisins contamination as a health benefit, yet other Fusarium toxins and aflatoxins show inconclusive results. For nutritionally altered crops (CS-4), the genetic modifications applied lead to compositional changes which require special considerations of their nutritional impacts. No health indicators were thus identified except for possible beneficial impacts of reduced mycotoxins and nutritional enhancement. More generally, veterinary health data should ideally be linked with animal exposure information so as to be able to establish cause-effect relationships.

Assessment of genetically modified maize NK603 x MON810 for renewal of authorisation under Regulation (EC) No 1829/2003 (application EFSA-GMO-RX-007).

Following the submission of application EFSA-GMO-RX-007 under Regulation (EC) No 1829/2003 from Monsanto, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application of the herbicide-tolerant and insect-resistant genetically modified maize NK603 x MON810. 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 sequence of the events in maize NK603 x MON810 considered for renewal is identical to the sequence of the originally assessed events, the GMO Panel concludes that there is no evidence in the renewal application EFSA-GMO-RX-007 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize NK603 x MON810.

Assessment of genetically modified maize MON 87403 for food and feed uses, import and processing, under Regulation (EC) No 1829/2003 (application EFSA-GMO-BE-2015-125).

Maize MON 87403 was developed to increase ear biomass at early reproductive phase through the expression of a modified AtHB17 gene from Arabidopsis thaliana, encoding a plant transcription factor of the HD-Zip II family. The molecular characterisation data and bioinformatic analyses did not identify issues requiring assessment for food and feed safety. No statistically significant differences in the agronomic and phenotypic characteristics tested between maize MON 87403 and its conventional counterpart were identified. The compositional analysis of maize MON 87403 did not identify differences that require further assessment. The GMO Panel did not identify safety concerns regarding the toxicity and allergenicity of the AtHB17∆113 protein, as expressed in maize MON 87403. The nutritional value of food and feed derived from maize MON 87403 is not expected to differ from that of food and feed derived from non-genetically modified (GM) maize varieties. Based on the outcome of the studies considered in the comparative analysis and molecular characterisation, the GMO Panel concludes that maize MON 87403 is as safe and nutritious as the conventional counterpart and the non-GM maize reference varieties tested. In the case of accidental release of viable maize MON 87403 grains into the environment, maize MON 87403 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 87403. In conclusion, the GMO Panel considers that maize MON 87403, 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.

Assessment of genetically modified cotton GHB614 × LLCotton25 × MON 15985 for food and feed uses, under Regulation (EC) No 1829/2003 (application EFSA-GMO-NL-2011-94).

The three-event stack cotton GHB614 × LLCotton25 × MON 15985 was produced by conventional crossing to combine three single cotton events, GHB614, LLCotton25 and MON 15985. The EFSA GMO Panel previously assessed the three single events and did not identify safety concerns. No new data on the single events that could lead to modification of the original conclusions on their safety were identified. Based on the molecular, agronomic, phenotypic and compositional characteristics, the combination of the single events and of the newly expressed proteins in the three-event stack cotton did not give rise to food and feed safety or nutritional issues. Food and feed derived from cotton GHB614 × LLCotton25 × MON 15985 are expected to have the same nutritional impact as those derived from the non-GM comparator. In the case of accidental release of viable GHB614 × LLCotton25 × MON 15985 cottonseeds into the environment, this three-event stack cotton would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of cotton GHB614 × LLCotton25 × MON 15985. In conclusion, the GMO Panel considers that cotton GHB614 × LLCotton25 × MON 15985, as described in this application, is as safe as the non-GM comparator with respect to potential effects on human and animal health and the environment.

Statement complementing the EFSA Scientific Opinion on application (EFSA-GMO-DE-2011-95) for the placing on the market of genetically modified maize 5307 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 from Syngenta Crop Protection AG taking into consideration an additional toxicological study.

The GMO Panel was previously not in the position to complete the food/feed safety assessment of maize 5307 due to an inadequate 28-day toxicity study necessary for an appropriate assessment of eCry3.1Ab protein. Following a mandate from the European Commission, the GMO Panel assessed a supplementary 28-day toxicity study in mice on the eCry3.1Ab protein (1,000 mg/kg body weight (bw) per day) to complement its scientific opinion on application EFSA-GMO-DE-2011-95 for the placing on the market of the maize 5307 for food and feed uses, import and processing. The supplementary 28-day toxicity study did not show adverse effects. Taking into account the previous assessment and the new information, the GMO Panel concludes that maize 5307, as assessed in the scientific opinion on application EFSA-GMO-DE-2011-95 (EFSA GMO Panel, 2015) and in the supplementary toxicity study, is as safe and nutritious as its conventional counterpart in the scope of this application.

Assessment of genetically modified maize 4114 for food and feed uses, under Regulation (EC) No 1829/2003 (application EFSA-GMO-NL-2014-123).

Maize 4114 was developed through Agrobacterium tumefaciens-mediated transformation to provide protection against certain lepidopteran and coleopteran pests by expression of the Cry1F, Cry34Ab1 and Cry35Ab1 proteins derived from Bacillus thuringiensis, and tolerance to the herbicidal active ingredient glufosinate-ammonium by expression of the PAT protein derived from Streptomyces viridochromogenes. The molecular characterisation data did not identify issues requiring assessment for food/feed safety. None of the compositional, agronomic and phenotypic differences identified between maize 4114 and the non-genetically modified (GM) comparator(s) required further assessment. There were no concerns regarding the potential toxicity and allergenicity of the newly expressed proteins Cry1F, Cry34Ab1, Cry35Ab1 and PAT, and no evidence that the genetic modification might significantly change the overall allergenicity of maize 4114. The nutritional value of food/feed derived from maize 4114 is not expected to differ from that derived from non-GM maize varieties and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable maize 4114 grains into the environment, maize 4114 would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize 4114. The genetically modified organism (GMO) Panel concludes that maize 4114 is as safe as the non-GM comparator(s) and non-GM reference varieties with respect to potential effects on human and animal health and the environment in the context of the scope of this application.

Assessment of genetically modified maize MON 87411 for food and feed uses, import and processing, under Regulation (EC) No 1829/2003 (application EFSA-GMO-NL-2015-124).

Maize MON 87411 was developed to confer resistance to corn rootworms (Diabrotica spp.) by the expression of a modified version of the Bacillus thuringiensis cry3Bb1 gene and a DvSnf7 dsRNA expression cassette, and tolerance to glyphosate-containing herbicides by the expression of a CP4 5-enolpyruvylshikimate-3-phosphate synthase (cp4 epsps) gene. The molecular characterisation data and bioinformatics analyses did not identify issues requiring assessment for food and feed safety. No statistically significant differences in the agronomic and phenotypic characteristics tested between maize MON 87411 and its conventional counterpart were identified. The compositional analysis of maize MON 87411 did not identify differences that required further assessment except for palmitic acid levels in grains from not treated maize MON 87411. The GMO Panel did not identify safety concerns regarding the toxicity and allergenicity of the Cry3Bb1 and CP4 EPSPS proteins, as expressed in maize MON 87411 and found no evidence that the genetic modification might significantly change the overall allergenicity of maize MON 87411. The nutritional impact of maize MON 87411-derived food and feed is expected to be the same as those derived from the conventional counterpart and non-GM commercial reference varieties. The GMO Panel concludes that maize MON 87411, as described in this application, is nutritionally equivalent to and as safe as the conventional counterpart and the 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 87411 grains into the environment, maize MON 87411 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 87411. The GMO Panel concludes that maize MON 87411, 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.

Technical Note on the quality of DNA sequencing for the molecular characterisation of genetically modified plants.

As part of the risk assessment (RA) requirements for genetically modified (GM) plants, according to Regulation (EU) No 503/2013 and the EFSA guidance on the RA of food and feed from GM plants (EFSA GMO Panel, 2011), applicants need to perform a molecular characterisation of the DNA sequences inserted in the GM plant genome. The European Commission has mandated EFSA to develop a technical note to the applicants on, and checking of, the quality of the methodology, analysis and reporting covering complete sequencing of the insert and flanking regions, insertion site analysis of the GM event, and generational stability and integrity. This Technical Note puts together requirements and recommendations for when DNA sequencing is part of the molecular characterisation of GM plants, in particular for the characterisation of the inserted genetic material at each insertion site and flanking regions, the determination of the copy number of all detectable inserts, and the analysis of the genetic stability of the inserts, when addressed by Sanger sequencing or NGS. This document reflects the current knowledge in scientific-technical methods for generating and verifying, in a standardised manner, DNA sequencing data in the context of RA of GM plants. From 1 October 2018, this Technical Note will replace the JRC guideline of 2016 (updated April 2017) related to the verification and quality assessment of the sequencing of the insert(s) and flanking regions. It does not take into consideration the verification and validation of the detection method which remains under the remit of the JRC.

Assessment of genetically modified maize 1507 × NK603 for renewal of authorisation under Regulation (EC) No 1829/2003 (application EFSA-GMO-RX-008).

Following the submission of application EFSA-GMO-RX-008 under Regulation (EC) No 1829/2003 from Pioneer Hi-Bred International, Inc. and Dow AgroSciences 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 insect-resistant, herbicide-tolerant genetically modified maize 1507 × NK603, for food and feed uses, import and processing, excluding cultivation within the EU. The data received in the context of this renewal application contained 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. In conclusion, under the assumption that the DNA sequence of the events in maize 1507 × NK603 considered for renewal are identical to the newly reported 1507 sequence and the NK603 sequence of the originally assessed two-event stack maize, the GMO Panel concludes that there is no evidence in the renewal application EFSA-GMO-RX-008 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize 1507 × NK603 (EFSA, 2006).

Assessment of genetically modified soybean MON 87751 for food and feed uses under Regulation (EC) No 1829/2003 (application EFSA-GMO-NL-2014-121).

Soybean MON 87751 was developed through Agrobacterium tumefaciens-mediated transformation to provide protection certain specific lepidopteran pests by the expression of the Cry1A.105 and Cry2Ab2 proteins derived from Bacillus thuringiensis. The molecular characterisation data and bioinformatic analyses did not identify issues requiring assessment for food and feed safety. None of the compositional, agronomic and phenotypic differences identified between soybean MON 87751 and the conventional counterpart required further assessment. The GMO Panel did not identify safety concerns regarding the toxicity and allergenicity of the Cry1A.105 and Cry2Ab2 proteins as expressed in soybean MON 87751, and found no evidence that the genetic modification might significantly change the overall allergenicity of soybean MON 87751. The nutritional impact of soybean MON 87751-derived food and feed is expected to be the same as those derived from the conventional counterpart and non-GM commercial reference varieties. The GMO Panel concludes that soybean MON 87751, as described in this application, is nutritionally equivalent to and as safe as the conventional counterpart and the non-GM soybean reference varieties tested, and no post-market monitoring of food and feed is considered necessary. In the case of accidental release of viable soybean MON 87751 seeds into the environment, soybean MON 87751 would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of soybean MON 87751. In conclusion, soybean MON 87751, as described in this application, 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.

Guidance on allergenicity assessment of genetically modified plants.

This document provides supplementary guidance on specific topics for the allergenicity risk assessment of genetically modified plants. In particular, it supplements general recommendations outlined in previous EFSA GMO Panel guidelines and Implementing Regulation (EU) No 503/2013. The topics addressed are non-IgE-mediated adverse immune reactions to foods, in vitro protein digestibility tests and endogenous allergenicity. New scientific and regulatory developments regarding these three topics are described in this document. Considerations on the practical implementation of those developments in the risk assessment of genetically modified plants are discussed and recommended, where appropriate.

Scientific opinion on an application for renewal of authorisation for continued marketing of maize 1507 and derived food and feed submitted under Articles 11 and 23 of Regulation (EC) No 1829/2003 by Pioneer Overseas Corporation and Dow AgroSciences LLC.

Following the submission of application EFSA-GMO-RX-001 under Regulation (EC) No 1829/2003 from Pioneer Overseas Corporation and Dow Agrosciences LLC, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) was asked to deliver a scientific risk assessment on the data submitted in the frame of a renewal of authorisation application of the insect-resistant and herbicide-tolerant genetically modified (GM) maize 1507. The data package received in the frame of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, an updated bioinformatics analysis and additional documents or studies performed by or on behalf of the applicant. The GMO Panel assessed this data package for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the frame of the original application. Under the assumption that the DNA sequence of the event in maize 1507 considered for renewal is identical to the corrected sequence of the originally assessed event, the GMO Panel concludes that no new hazards or modified exposure and no new scientific uncertainties were identified for the application for renewal that would change the conclusions of the original risk assessment on maize 1507 (EFSA, 2005b, 2009).

Assessment of genetically modified maize GA21 for renewal of authorisation under Regulation (EC) No 1829/2003 (application EFSA-GMO-RX-005).

Following the submission of application EFSA-GMO-RX-005 under Regulation (EC) No 1829/2003 from Syngenta Crop Protection NV/SA, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application of the herbicide-tolerant genetically modified maize GA21. The data received in the context of this renewal application contained post-market environmental monitoring reports, a systematic search and evaluation of literature, updated bioinformatics 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 sequence of the event in maize GA21 considered for renewal is identical to the corrected sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in the renewal application EFSA-GMO-RX-005 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on maize GA21.

Assessment of genetically modified maize 1507 × 59122 × MON810 × NK603 and subcombinations, for food and feed uses, under Regulation (EC) No 1829/2003 (application EFSA-GMO-NL-2011-92).

In this opinion, the GMO Panel assessed the four-event stack maize 1507 × 59122 ×  MON810 ×  NK603 and its ten subcombinations, independently of their origin. The GMO Panel previously assessed the four single events combined in this four-event stack maize and five of their combinations and did not identify safety concerns. No new data on the single events or their previously assessed combinations leading to modification of the original conclusions were identified. Based on the molecular, agronomic, phenotypic and compositional characteristics, the combination of the single maize events and of the newly expressed proteins in the four-event stack maize did not give rise to food and feed safety or nutritional issues. The GMO Panel concludes that the four-event stack maize is as safe and as nutritious as its non-GM comparator. In the case of accidental release of viable grains of maize 1507 × 59122 × MON810 × NK603 into the environment, this would not raise environmental safety concerns. For four of the subcombinations not previously assessed, protein expression data were provided and did not indicate an interaction affecting the levels of the newly expressed proteins in these subcombinations. The five subcombinations not previously assessed are expected to be as safe as the single maize events, the previously assessed subcombinations and the four-event stack maize. The GMO Panel considers that post-market monitoring of maize 1507 × 59122 ×MON810 × NK603 and its subcombinations is not necessary. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of maize 1507 × 59122 × MON810 ×NK603 and its subcombinations.

Guidance for the risk assessment of the presence at low level of genetically modified plant material in imported food and feed under Regulation (EC) No 1829/2003.

This document provides guidance for the risk assessment under Regulation (EC) No 1829/2003 of the unintended, adventitious or technically unavoidable presence in food and feed of low level of genetically modified plant material intended for markets other than in the European Union. In this context, the presence at low level is defined to be maximum 0.9% of genetically modified plant material per ingredient. This guidance is intended to assist applicants by indicating which scientific requirements of Annex II of Regulation (EU) No 503/2013 are considered necessary for the risk assessment of the presence at low levels of genetically modified plant material in food and feed.

Assessment of genetically modified sugar beet H7-1 for renewal of authorisation under Regulation (EC) No 1829/2003 (application EFSA-GMO-RX-006).

Following the submission of application EFSA-GMO-RX-006 under Regulation (EC) No 1829/2003 from KWS SAAT SE and Monsanto Company, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) 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 sugar beet H7-1. The data received in the context of this renewal application contained a systematic search and evaluation of literature, updated bioinformatics 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 sequence of the event in sugar beet H7-1 considered for renewal is identical to the originally assessed event, the GMO Panel concludes that there is no evidence in the context of this renewal application for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on sugar beet H7-1.

Assessment of genetically modified oilseed rape MS8, RF3 and MS8×RF3 for renewal of authorisation under regulation (EC) No 1829/2003 (application EFSA-GMO-RX-004).

Following the submission of application EFSA-GMO-RX-004 under Regulation (EC) No 1829/2003 from Bayer CropScience, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application of the genetically modified (GM) herbicide-tolerant oilseed rape MS8, RF3 and MS8×RF3. The data received in the context of this renewal application contain post-market environmental monitoring reports, systematic searches and evaluation of literature, updated bioinformatics 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 sequence of the event in oilseed rape MS8, RF3 and MS8×RF3 considered for renewed authorisation is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in the context of this renewal application 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.