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Soybean DAS-81419-2 was developed by Agrobacterium tumefaciens-mediated transformation. It expresses the Cry1F and Cry1Ac proteins to confer resistance to certain lepidopteran species and the PAT protein that confers tolerance to glufosinate ammonium-based herbicides and that was used as a selectable marker gene. The molecular characterisation of soybean DAS-81419-2 did not give rise to safety issues. The agronomic, phenotypic and compositional characteristics of soybean DAS-81419-2 tested under field conditions revealed no relevant differences between soybean DAS-81419-2 and its conventional counterpart that would give rise to any food and feed or environmental safety concerns. There were no concerns regarding the potential toxicity and allergenicity of the newly expressed proteins Cry1F, Cry1Ac and PAT, and no evidence that the genetic modification might significantly change the overall allergenicity of soybean DAS-81419-2. The nutritional value of soybean DAS-81419-2 is not expected to differ from that of non-GM soybean varieties and no post-market monitoring of food/feed is considered necessary. There are no indications of an increased likelihood of establishment and spread of occasional feral soybean DAS-81419-2 plants, unless these plants are exposed to glufosinate ammonium-based herbicides or infested by insect pests that are susceptible to the Cry1F and Cry1Ac proteins. This will not result in different environmental impacts compared to conventional soybean. Considering the scope of this application, interactions with the biotic and abiotic environment were not considered to be an issue. Risks associated with an unlikely but theoretically possible horizontal gene transfer from soybean DAS-81419-2 to bacteria have not been identified. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of soybean DAS-81419-2. The GMO Panel concludes that the soybean DAS-81419-2 is as safe and as nutritious as its conventional counterpart and the tested non-GM reference varieties in the context of its scope. [ABSTRACT FROM AUTHOR]

The EFSA Panel on Genetically Modified Organisms (GMO Panel) has previously assessed genetically modified (GM) maize DAS-59122-7 as a single event as well as part of several stacked events. These maize events were found to be as safe as their conventional counterparts and other appropriate comparators with respect to potential effects on human and animal health, and the environment. On 26 July 2016, the European Commission received from Pioneer new nucleic acid sequencing data on maize event DAS-59122-7 and updated bioinformatic analyses using the new sequencing data. The European Commission tasked EFSA to analyse these data and to indicate whether the previous conclusions of the GMO Panel on the previously assessed GM maize events remain valid. The GMO Panel used the appropriate principles described in its guidelines for the risk assessment of GM plants to analyse the received data. The new sequencing data indicated three base pair (bp) differences compared to the sequencing data originally provided; two located in a non-coding region of the insert and one located in the 50 genomic flanking region. These base pairs reported as differences in the new nucleic acid sequencing data on maize event DAS-59122-7 had already been present in the original plant material used for the risk assessment. Thus, with the exception of bioinformatics analyses, the studies performed for the risk assessment remain valid. The new sequencing data and the bioinformatic analyses performed on the new sequence did not give rise to safety issues. Therefore, the GMO Panel concludes that the original risk assessment of event DAS-59122-7 as a single and as a part of stacked events remains valid. [ABSTRACT FROM AUTHOR]

Maize DAS-40278-9 was developed by direct Whiskers-mediated transformation to express the aryloxyalkanoate dioxygenase-1 (AAD-1) protein, conferring tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) and aryloxyphenoxypropionate (AOPP) herbicides. The molecular characterisation of maize DAS-40278-9 did not raise safety issues. The agronomic, phenotypic and compositional characteristics of maize DAS-40278-9 tested under field conditions revealed no differences between maize DAS-40278-9 and its non-genetically modified (GM) comparator that would give rise to food and feed or environmental safety concerns. There were no concerns regarding the potential toxicity and allergenicity of the newly expressed protein AAD-1, and no evidence that the genetic modification might significantly change the overall allergenicity of maize DAS-40278-9. The nutritional characteristics of maize DAS-40278-9 are not expected to differ from those of non-GM maize varieties and no post-market monitoring of food/feed is considered necessary. Maize DAS-40278-9 is as nutritious as its non-GM comparator and other non-GM commercial varieties. There are no indications of an increased likelihood of establishment and spread of occasional feral maize DAS-40278-9 plants, unless these plants are exposed to the intended herbicides. However, this will not result in different environmental impacts compared to conventional maize. Considering the scope of the application, interactions with the biotic and abiotic environment were not considered an issue. Risks associated with the unlikely but theoretically possible horizontal gene transfer from maize DAS-40278-9 to bacteria were not identified. The post-market environmental monitoring plan and reporting intervals are in line with the scope of the application. In conclusion, the EFSA GMO Panel considers that the information available for maize DAS-40278-9 addresses the scientific comments raised by the Member States and that maize DAS-40278-9, as described in this application, is as safe as the non-GM comparator and non-GM maize reference varieties with respect to potential effects on human and animal health and the environment in the context of the scope of this application. [ABSTRACT FROM AUTHOR]

Proteins of the 2S albumin family, such as Ara h2 and Ara h6, are most frequently involved in peanut allergy. We have developed a reverse enzyme allergo-sorbent test (EAST) in which total serum IgE antibodies are first captured by immobilised anti-human IgE monoclonal antibodies, and then the binding of the anti-Ara h2 and anti-Ara h6 specific IgE to the corresponding labelled allergens is measured. This reverse immunoassay was used either as a direct EAST or as an EAST inhibition assay to study the interactions of whole peanut protein extract and purified Ara h2 and Ara h6 with IgE antibodies from peanut-allergic patients. Finally, we identified some IgE-binding epitopes on Ara h6 using a format of EAST in which the protein is immobilised in a particular, well defined, manner through interactions with specific monoclonal antibodies (mAbs) coated on the micro-plates. The fine specificity of those mAbs has been characterised at the epitope level, and their binding to the allergen thus masks a known particular epitope and makes it unavailable for recognition by IgE antibodies. The reverse EAST increased the ratio specific signal/background. It avoids interferences with competitors such as anti-peanut protein IgG antibodies and allows the study of the specificity and/or affinity of the interactions between IgE antibodies and Ara h2 or Ara h6 with a higher sensitivity and accuracy than the conventional EAST. The EAST results obtained when the allergens are presented by specific mAbs suggest that the homologous molecular domain(s) in peanut 2S albumins encompass major IgE epitope(s) and are strongly involved in peanut allergenicity. [ABSTRACT FROM AUTHOR]

The use of the food-grade bacterium Lactococcus lactis as a DNA delivery vehicle at the mucosal level is an attractive DNA vaccination strategy. Previous experiments showed that recombinant L. lactis expressing the Listeria monocytogenes inlA gene can deliver a functional gene into mammalian cells. Here, we explored the potential use of noninvasive L. lactis strains as a DNA delivery vehicle. We constructed two Escherichia coli-L. lactis shuttle plasmids, pLIG:BLG1 and pLIG:BLG2, containing a eukaryotic expression cassette with the cDNA of bovine β-lactoglobulin (BLG). The greatest BLG expression after transfection of Cos-7 cells was obtained with pLIG:BLG1, which was then used to transform L. lactis MG1363. The resulting L. lactis strain MG1363(pLIG:BLG1) was not able to express BLG. The potential of L. lactis as a DNA delivery vehicle was analyzed by detection of BLG in Caco-2 human colon carcinoma cells after 3 h of coincubation with (i) purified pLIG:BLG1, (ii) MG1363(pLIG:BLG1), (iii) a mix of MG1363(pLIG) and purified pLIG:BLG1, and (iv) MG1363. Both BLG cDNA and BLG expression were detected only in Caco-2 cells coincubated with MG1363(pLIG:BLG1). There was a decrease in the BLG cDNA level in Caco-2 cells between 24 and 48 h after coincubation. BLG expression by Caco-2 cells started at 24 h and increased between 24 and 72 h. BLG secretion by Caco-2 cells started 48 h after coincubation with MG1363(pLIG:BLG1). We conclude that lactococci can deliver BLG cDNA into mammalian epithelial cells, demonstrating their potential to deliver in vivo a DNA vaccine. [ABSTRACT FROM AUTHOR]

Abstract: Free radical reactions are involved in the pathogenesis of numerous diseases, so there is a real need to develop biomarkers that reflect these reactions in vivo. 4-Hydroxy-2-nonenal (HNE) is a major product of the lipid peroxidation process that is a consequence of free radical reactions. We present here the development and validation of an enzyme immunoassay (EIA) of the major urinary metabolite of HNE, namely 1,4-dihydroxynonane-mercapturic acid (DHN-MA). EIA allowed direct measurement of DHN-MA in rat urine with good sensitivity (0.02 ng/ml) and precision (intraassay CV = 5.7%). Recovery was complete (99–102%). Cross-reactivity was very low with 1,4-dihydroxynonene and with different mercapturic acids except with one other HNE urinary metabolite. Good correlation (EIA = 0.79 × LC/MS + 14.03, r = 0.877, p < 10−8) was obtained between EIA and liquid chromatography/mass spectrometry (LC/MS) quantitation when analyzing urine samples of rats with different oxidative status, due to treatment with either BrCCl3 or trinitrobenzene sulfonic acid, which are known to induce hepatic lipid peroxidation or colon inflammation, respectively. [Copyright &y& Elsevier]

Bovine β-lactoglobulin (Blg) is one of the major cow's milk allergens. Peptide 41-60 of Blg (Blg41-60) was described as a murine T-cell determinant and a murine, rat, and human immunoglobulin E (IgE) epitope. The aim of this study was the expression of Blg41-60 as a fusion protein in the food-grade bacterium Lactococcus lactis and the characterization of its immunogenicity in mice. We constructed a recombinant strain of L. lactis capable of inducible production and secretion of Blg41-60::Nuc, a fusion protein between Blg41-60 and the mature part of the staphylococcal nuclease (Nuc). The highest production yield of BIg41-60::Nuc (32.5 mg/liter) was reached 4 h after induction. At this time, up to 75% of Blg41-60::Nuc was secreted. When monoclonal antibodies specific for Blg41-60 were used, purified Blg41-60::Nuc and synthetic Blg41-60 exhibited very similar immunoreactivities. Subcutaneous coadministration of purified Blg41-60::Nuc and killed nonrecombinant L. lactis resulted in the induction of specific anti-Blg41-60 IgG2a and IgG1. The IgG1/IgG2a ratio and the lack of specific IgE suggest a Th1-type immune response, i.e., a nonallergic response. Similar administrations of the killed Blg41-60::Nuc-producing L. lactis strain did not elicit a specific immune response, whereas a transitory mucosal IgA-specific immune response was induced in mice after oral administration of the live Blg41-60:: Nuc-producing L. lactis strain. [ABSTRACT FROM AUTHOR]

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., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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)., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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., (© 2018 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

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., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

In this opinion, the GMO Panel assessed the five-event stack maize MON 87427 × MON 89034 ×1507 × MON 88017 × 59122 and its 25 subcombinations, independently of their origin. The GMO Panel has previously assessed the five single events combined to produce this five-event stack maize and 11 subcombinations of these events and did not identify safety concerns. No new data on the single events or their previously assessed subcombinations, leading to modification of the original conclusions were identified. The combination of the single events and of the newly expressed proteins in the five-event stack maize did not give rise to issues - based on the molecular, agronomic/phenotypic or compositional characteristics - regarding food and feed safety and nutrition. Considering the scope of this application, the known biological function of the newly expressed proteins and the data available for the five-event stack maize and its previously assessed maize subcombinations, the GMO Panel considered that different combinations of the single events would not raise environmental concerns. The GMO Panel concludes that the five-event stack maize is as safe and as nutritious as the non-genetically modified (GM) comparator and the tested non-GM reference varieties in the context of its scope. For the 14 maize subcombinations for which no experimental data were provided, the GMO Panel assessed the likelihood of interactions among the single events, and concluded that their combinations would not raise safety concerns. These maize subcombinations are therefore expected to be as safe as the single events, the previously assessed subcombinations and maize MON 87427 ×MON 89034 × 1507 × MON 88017 × 59122. Since the post-market environmental monitoring plan for the five-event stack maize does not include any provisions for the 14 maize subcombinations not previously assessed, the GMO Panel recommended the applicant to revise the plan accordingly., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

In this opinion, the EFSA Panel on Genetically Modified Organisms (GMO Panel) assessed the three-event stack maize MON 87427 × MON 89034 × NK603 and its three subcombinations, independently of their origin. The GMO Panel has previously assessed the three single events combined to produce this three-event stack maize and did not identify safety concerns. No new data on the single events, leading 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 maize events and of the newly expressed proteins in the three-event stack maize did not give rise to issues regarding food and feed safety or nutrition. In the case of accidental release of viable grains of maize MON 87427 × MON 89034 × NK603 into the environment, the three-event stack maize would not raise environmental safety concerns. The GMO Panel concludes that the three-event stack maize is as safe and as nutritious as the non-GM comparator and the tested non-GM reference varieties in the context of its scope. The GMO Panel considered that its previous conclusions on the two-event stack maize MON 89034 × NK603 remain valid. For the two maize subcombinations for which no experimental data were provided the GMO Panel assessed the likelihood of interactions among the single events, and concluded that their combination would not raise safety concerns. These two subcombinations are therefore expected to be as safe as the single events, the previously assessed maize MON 89034 × NK603 and maize MON 87427 × MON 89034 × NK603. Since the post-market environmental monitoring plan for the three-event stack maize does not include any provisions for the two subcombinations not previously assessed, the GMO Panel recommended the applicant to revise the plan accordingly., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following the submission of application EFSA-GMO-RX-003 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 context of the renewal of authorisation application of the insect-resistant genetically modified maize 59122. 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 59122 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 that would change the conclusions of the original risk assessment on maize 59122., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Following a request from the European Commission, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) assessed the annual post-market environmental monitoring (PMEM) report for the 2015 growing season of the Cry1Ab-expressing maize event MON 810 provided by Monsanto Europe S.A. The GMO Panel concludes that the insect resistance monitoring data submitted to EFSA do not indicate a decrease in susceptibility of field Iberian populations of corn borers to the Cry1Ab protein during the 2015 season. However, since the methodology for insect resistance monitoring remained unchanged compared to previous PMEM reports, the GMO Panel reiterates its previous recommendations on resistance monitoring to provide sufficient detection sensitivity. Although the farmer alert system to report complaints about product performance could complement the information obtained from the laboratory bioassays, the GMO Panel is currently not in a position to appraise its usefulness, and therefore encourages the consent holder to provide more information on this complementary resistance monitoring tool. The data on general surveillance (GS) do not indicate any unanticipated adverse effects on human and animal health or the environment arising from the cultivation of maize MON 810. The GMO Panel reiterates its previous recommendations on the analysis of farmer questionnaires, and advises the consent holder to provide more detailed information on the conducting and reporting of the literature search in future annual PMEM reports. Moreover, the GMO Panel encourages relevant parties to continue developing a methodological framework to use existing networks in the broader context of environmental monitoring. The GMO Panel concludes that the case-specific monitoring (CSM) and GS activities of maize MON 810 as carried out by the consent holder do not provide evidence that would invalidate previous GMO Panel evaluations on the safety of maize MON 810., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

In this opinion, the GMO Panel assessed the three-event stack oilseed rape (OSR) MON 88302 × MS8 × RF3 and its three subcombinations, independently of their origin. The GMO Panel has previously assessed the single events combined to produce this three-event stack OSR and did not identify safety concerns; no new information that would modify the original conclusions was identified. The combination of the single OSR events and of the newly expressed proteins in the three-event stack OSR does not give rise to food and feed safety and nutrition issues - based on the molecular, agronomic/phenotypic and compositional characteristics. In the case of accidental release of viable OSR MON 88302 × MS8 × RF3 seeds into the environment, the three-event stack OSR would not raise environmental safety concerns. The GMO Panel therefore concluded that the three-event stack OSR is as safe and as nutritious as its conventional counterpart and the tested non-GM reference varieties in the context of the scope of this application. Since no new safety concerns were identified for the previously assessed two-event stack OSR MS8 × RF3, the GMO Panel considered that its previous conclusions on this subcombination remain valid. For the two subcombinations MON 88302 × MS8 and MON 88302 × RF3 for which no experimental data were provided, the GMO Panel assessed the likelihood of interactions among the single events, and concluded that their different combinations would not raise safety concerns. These two subcombinations are therefore expected to be as safe as the single events, the previously assessed OSR MS8 × RF3, and OSR MON 88302 × MS8 × RF3. Since the post-market environmental monitoring plan for the three-event stack OSR does not include any provisions for two subcombinations not previously assessed, the GMO Panel recommended the applicant to revise the plan accordingly., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)

Recommendations and guidelines on the prevention of food allergy have changed in recent decades. The aim of this review of the current evidence and ongoing studies is to provide a comprehensive and up to date picture of prevention of food allergy for healthcare professionals. The review was undertaken as part of the European Union funded Integrated Approaches to Food Allergy and Allergen Management (iFAAM) study. This is a wide ranging project bringing together expertise across the breadth of food allergy research. Specifically, the review discusses dietary manipulation in food allergy prevention, and covers the possible preventive strategies of allergen avoidance, early allergen introduction, general nutrition and supplements, as well as other strategies, such as prebiotics and probiotics. The review concludes that despite agreement that allergen avoidance strategies should not be undertaken for allergy prevention, there is currently no consensus regarding what actions should be recommended beyond exclusive breastfeeding for the first 4-6 months of life. Recent and upcoming trial results, which are detailed in this review, should help inform the debate and add clarity to the topic., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

In January 2014, an international meeting sponsored by the International Life Sciences Institute/Health and Environmental Sciences Institute and the Canadian Food Inspection Agency titled "Genetic Basis of Unintended Effects in Modified Plants" was held in Ottawa, Canada, bringing together over 75 scientists from academia, government, and the agro-biotech industry. The objectives of the meeting were to explore current knowledge and identify areas requiring further study on unintended effects in plants and to discuss how this information can inform and improve genetically modified (GM) crop risk assessments. The meeting featured presentations on the molecular basis of plant genome variability in general, unintended changes at the molecular and phenotypic levels, and the development and use of hypothesis-driven evaluations of unintended effects in assessing conventional and GM crops. The development and role of emerging "omics" technologies in the assessment of unintended effects was also discussed. Several themes recurred in a number of talks; for example, a common observation was that no system for genetic modification, including conventional methods of plant breeding, is without unintended effects. Another common observation was that "unintended" does not necessarily mean "harmful". This paper summarizes key points from the information presented at the meeting to provide readers with current viewpoints on these topics.

Background: The 2S-albumin Ara h 2 is the most potent peanut allergen and a good predictor of clinical reactivity in allergic children. Posttranslational hydroxylation of proline residues occurs in DPYSP(OH)S motifs, which are repeated 2 or 3 times in different isoforms., Objectives: We investigated the effect of proline hydroxylation on IgE binding and the relative contributions of linear and conformational epitopes to Ara h 2 allergenicity., Methods: Peptides containing DPYSP(OH)S motifs were synthesized. A recombinant variant of Ara h 2 without DPYSP(OH)S motifs was generated by means of deletion mutagenesis. IgE reactivity of 18 French and 5 American patients with peanut allergy toward synthetic peptides and recombinant allergens was assessed by using IgE-binding inhibition assays and degranulation tests of humanized rat basophilic leukemia cells., Results: Hydroxyproline-containing peptides exhibited an IgE-binding activity equivalent to that of the unfolded Ara h 2. In contrast, corresponding peptides without hydroxyprolines displayed a very weak IgE-binding capacity. Despite removal of the DPYSP(OH)S motifs, the deletion variant still displayed Ara h 2 conformational epitopes. The IgE-binding capacity of Ara h 2 was then recapitulated with an equimolar mixture of a hydroxylated peptide and the deletion variant. Hydroxylated peptides of 15 and 27 amino acid residues were also able to trigger cell degranulation., Conclusions: Sensitization toward linear and conformational epitopes of Ara h 2 is variable among patients with peanut allergy. Optimal IgE binding to linear epitopes of Ara h 2 requires posttranslational hydroxylation of proline residues. The absence of hydroxyprolines could then affect the accuracy of component-resolved diagnostics by using rAra h 2., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu ) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event.

Scope: Cow's milk allergy is the most prevalent food allergy in infants whose immune system development is critically stimulated during postnatal gut colonization by commensal bacteria. Allergenic potential of cow's milk β-lactoglobulin (BLG) and caseins (CAS) was investigated in germ-free (GF) BALB/c mice and in GF mice conventionalized (CVd) at 6 weeks of age., Methods and Results: Oral sensitization to cow's milk in the presence of cholera toxin led to higher BLG-specific IgE, IgG1, and IgG2a responses in GF mice than in conventional (CV) mice. No significant difference was observed for CAS-specific IgE responses although IgG1 responses to αS1- and κ-caseins were higher in GF mice than in CV mice. CVd mice, orally inoculated with fecal preparations from CV mice, also displayed biased antibody responses compared to CV mice. Secretion of Th2 cytokines by BLG- and CAS-reactivated splenocytes of CVd mice was similar to that of GF mice whereas cytokine production by reactivated cells from mesenteric lymph nodes of CVd mice was equivalent to that of CV mice., Conclusion: Oral sensitization to BLG and CAS was differentially affected by the absence of gut microbiota and delayed bacterial colonization altered persistently the host immune response to oral sensitization against food antigens., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Despite a sequence homology of 90% between bovine and caprine β-caseins (CN), IgE antibodies from patients allergic to goat's milk (GM), but tolerant to cow's milk (CM), recognize caprine β-CN without cross-reacting with bovine β-CN. We investigated this lack of cross-reactivity by evaluating the IgE-reactivity toward peptides isolated from plasmin hydolysates of bovine and caprine β-CN., Methods and Results: The IgE-binding capacity of plasmin-derived peptides was evaluated with sera from 10 CM-allergic patients and 12 GM-allergic/CM-tolerant patients. In CM-allergic patients, IgE reactivity of caprine fragments (f29-107) and (f108-207), but not (f1-28), was similar to that of the bovine counterparts. In contrast, all bovine fragments were poorly recognized by IgE antibodies from GM-allergic/CM-tolerant patients. The peptide (f29-107) was generally the most immunoreactive fragment of caprine β-CN. By using synthetic peptides, the immunodominant IgE-binding epitope recognized by most GM-allergic/CM-tolerant patients was located in the caprine domain 49-79., Conclusion: The restricted specificity of the IgE response toward the caprine β-CN in GM-allergic/CM-tolerant patients is mainly directed against the domain 49-79, which differs from its bovine counterpart by only three amino acid substitutions., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: 2S-albumins Ara h 2 and Ara h 6 are the most widely recognized and potent allergens for peanut-allergic patients. These allergens are particularly resistant to proteolysis and the digestion products generally retain significant allergenicity. Five disulfide bridges (DB) stabilize Ara h 6 overall structure and their influence on the trypsin resistance and on the allergenicity of the digestion products was investigated., Methods and Results: Progressive disruption of each DB was performed by site-directed mutagenesis. Successful refolding of Ara h 6 variants was confirmed by circular dichroism. Trypsin resistance, IgE-binding capacity and allergenic potency, as assessed by in vitro mediator release assay with sera from peanut-allergic patients, was not affected by the deletion of the C-terminal DB at Cys(84) -Cys(124) . Additional disruption of DB at Cys(14) -Cys(71) or at Cys(73) -Cys(115) rendered Arg(16/20) or Arg(114) susceptible to trypsinolysis, respectively, but affected principally the IgE-binding capacity of Ara h 6. DB disruption at Cys(26) -Cys(58) or at Cys(59) -Cys(107) led to an extensive proteolytic degradation and a complete loss of allergenic potency of the digestion products., Conclusion: Selective disruption of the DB stabilizing the protease-resistant core of Ara h 6 eliminated the IgE-binding capacity of the trypsin-degradation products and their ability to trigger mast cell degranulation., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Roasting rather than boiling and Maillard modifications may modulate peanut allergenicity. We investigated how these factors affect the allergenic properties of a major peanut allergen, Ara h 1., Methods and Results: Ara h 1 was purified from either raw (N-Ara h 1) or roasted (R-Ara h 1) peanuts. Boiling (100°C 15 min; H-Ara h 1) resulted in a partial loss of Ara h 1 secondary structure and formation of rod-like branched aggregates with reduced IgE-binding capacity and impaired ability to induce mediator release. Glycated Ara h 1 (G-Ara h 1) formed by boiling in the presence of glucose behaved similarly. However, H- and G-Ara h1 retained the T-cell reactivity of N-Ara h 1. R-Ara h 1 was denatured, comprised compact, globular aggregates, and showed no evidence of glycation but retained the IgE-binding capacity of the native protein., Conclusion: Ara h 1 aggregates formed by boiling were morphologically distinct from those formed by roasting and had lower allergenic activity. Glycation had no additional effect on Ara h 1 allergenicity compared with heating alone. Taken together with published data on the loss of Ara h 2/6 from boiled peanuts, this supports the hypothesis that boiling reduces the allergenicity of peanuts., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: In most animal models of allergy, the development of an IgE response requires the use of an adjuvant. Germ-free (GF) mice exhibit Th2-polarized antibody responses combined with defective immunosuppressive mechanisms. The sensitizing potential of milk proteins was investigated in GF mice in the absence of adjuvant., Methods and Results: β-lactoglobulin (BLG) and whole casein (CAS) allergenicity was evaluated by means of intraperitoneal injections without adjuvant. Injections of BLG induced significant IgE and IgG1 responses in GF mice, while CAS injections provoked the production of IgG1 toward κ- and αS1-caseins. No significant antibody response was evidenced in conventional (CV) mice. After in vitro BLG-reactivation, IL-4, IL-5, IL-13 and IFN-γ productions by splenocytes were higher in GF mice than in CV mice. Heat-treatment decreased BLG allergenicity as indicated by the absence of IgE production in GF mice. However, heat-treatment increased protein immunogenicity and led to the production of anti-BLG and anti-κ-casein IgG1 in both GF and CV mice. This correlated with enhanced productions of IL-4, IL-5 and IL-13 in BLG-reactivated splenocytes from CV mice., Conclusion: Gut colonization by commensal bacteria appeared then to significantly reduce the susceptibility of mice toward the intrinsic allergenic and immunogenic potential of milk proteins., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cow's milk (CM) allergy affects about 2% of infants. The allergenicity of dietary proteins, including those from CM, has been related to their digestibility although the generality of the link and its causality remains to be demonstrated. In this study we use an in vitro digestion system, to investigate the digestibility of β-lactoglobulin (blg) during gastrointestinal transit and to assess the impact of this process on blg allergenic reactivity in CM allergic children., Methods: Blg digesta were prepared using an in vitro digestion protocol simulating either gastric digestion alone or followed by duodenal digestion with or without phosphatidylcholine (PC). Biochemical analysis of blg digesta was performed by SDS-PAGE and their concentration was measured by a sandwich ELISA. Assessment of their allergenic reactivity was done in vitro by EAST inhibition, specific basophil activation (basotest) and lymphocyte proliferation (PCNA-flow cytometry) assays using sera and cells from patients allergic to blg and in vivo by skin prick testing (SPT) of these patients., Results: Blg was only broken down to smaller peptides after gastro-duodenal digestion although a sizeable amount of intact protein still remained. Digestion did not modify the IgE binding capacity of blg except for gastro-duodenal digestion performed in the absence of PC. These results are consistent with the quantity of intact blg remaining in the digesta. Overall both gastric and gastroduodenal digestion enhanced activation of sensitized basophils and proliferation of sensitized lymphocytes by blg. However, there was a tendency towards reduction in mean diameter of SPT following digestion, the PC alone during phase 1 digestion causing a significant increase in mean diameter., Conclusions: Digestion did not reduce the allergenic reactivity of blg to a clinically insignificant extent, PC inhibiting digestion and thereby protecting blg allergenic reactivity. SPT reactivity was reduced compared to blg immunoreactivity in in vitro tests.

Highly purified allergens namely cow's milk alpha-lactalbumin (ALA). (Bos d 4), beta-lactoglobulin (BLG) (Bos d 5) and casein (Bos d 8) and goat's milk casein were prepared from the raw milk from a single animal with a known genetic background. Consequently the natural isoforms are limited, constant and characterized. Purification included selective precipitations and chromatographical steps. Characterization of structure and allergenic activity assessment of milk allergens were carried out using physicochemical and immunochemical methods. Taken together data demonstrated the absence of impurities and of contamination by other milk allergens in each preparation. NMR and circular dichroism analyses confirmed the native conformation and proper folding of ALA and BLG and the expected absence of folding of bovine and caprine casein. Enzyme immuno assays confirmed the native conformation of BLG and the purity and immunoreactivity of all the proteins. The allergenic activity, e. g. the IgE binding capacity, of purified proteins was identical as that of those proteins when present in milk. The purified proteins also demonstrated the ability to provoke the degranulation of humanized rat basophilic leukaemia cells. All the data thus confirm the purity, identity, structural conformation and functionality of the prepared milk allergens.