Food/Feed and Environmental Risk Assessment of Insect Resistant Genetically Modified Maize MON810 for Cultivation, Seed Production, Import, Processing and Feed Uses under Directive 2001/18/EC (Notification C/F/95/12/02)

In preparation for a legal implementation of EU-regulation 1829/2003, the Norwegian Environment Agency (former Norwegian Directorate for Nature Management) has requested the Norwegian Food Safety Authority (NFSA) to give final opinions on all genetically modified organisms (GMOs) and products containing or consisting of GMOs that are authorized in the European Union under Directive 2001/18/EC or Regulation 1829/2003/EC within the Authority’s sectoral responsibility.  The Norwegian Food Safety Authority has therefore, by letter dated 13 February 2013 (ref. 2012/150202), requested the Norwegian Scientific Committee for Food Safety (VKM) to carry out scientific risk assessments of 39 GMOs and products containing or consisting of GMOs that are authorized in the European Union. The request covers scope(s) relevant to the Gene Technology Act. The request does not cover GMOs that VKM already has conducted its final risk assessments on. However, the Agency requests VKM to consider whether updates or other changes to earlier submitted assessments are necessary.  MON810 notification C/F/95/12-02 is approved under Directive 90/220/EEC for cultivation, seed production, import and processing into feeding stuffs and industrial purposes since 22 April 1998 (Commission Decision 98/294/EC). In December 1997, food and food ingredients derived from the progeny of maize line MON810 were notified under Article 5 of Regulation (EC) No 258/97 on novel foods and novel food ingredients. In addition, existing food and feed products containing, consisting of or produced from MON810 were notified according to Articles 8 and 20 of Regulation (EC) No 1829/2003 and were placed in the Community Register in 2005.   Three applications for renewal of the authorisation for continued marketing of (1) existing food and food ingredients produced from MON810; (2) feed consisting of and/or containing maize MON810, and MON810 for feed use (including cultivation); and (3) food and feed additives, and feed materials produced from maize MON810 within the framework of Regulation (EC) No 1829/2003 were submitted in 2007.   Maize MON810 has previously been assessed by the VKM GMO Panel commissioned by the Norwegian Environment Agency in connection with the national finalisation of the procedure of the notification C/F/95/12/02 (VKM 2007a,b). In addition, MON810 has been evaluated by the VKM GMO Panel as a component of several stacked GM maize events (VKM 2005a,b,c, VKM 2007c, VKM 2008, VKM 2009, VKM 2012a). Due to the publication of new scientific literature and updated guidance for food/feed and environmental risk assessment of genetically modified plants, the VKM GMO Panel has decided to deliver an updated risk assessment of MON810.  The updated risk assessment of the maize MON810 is based on information provided by the applicant in the notification C/F/95/12/02 and application EFSA/GMO/RX/MON810, and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered other peer-reviewed scientific literature as relevant.    The VKM GMO Panel has evaluated MON810 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The VKM GMO panel has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2006, 2011a), the environmental risk assessment of GM plants (EFSA 2010), and the selection of comparators for the risk assessment of GM plants (EFSA 2011b).   The scientific risk assessment of maize MON810 includes molecular characterisation of the transformation process, vector construction, expression, inheritance and stability of the transgene construct, comparative assessment of agronomic and phenotypic characteristics, nutritional assessments, toxicology and  allergenicity, unintended effects on plant fitness, potential for gene transfer, interactions between the GM plant and target and non-target organisms and effects on biogeochemical processes.  It is emphasized that the VKM mandate does not include assessments of contribution to sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act. These considerations are therefore not part of the risk assessment provided by the VKM Panel on Genetically Modified Organisms.   The genetically modified maize MON810 was developed to provide protection against certain lepidopteran target pests, including European corn borer (Ostrinia nubilalis) and species belonging to the genus Sesamia. Protection is achieved through expression in the plant of the insecticidal Cry protein, Cry1Ab, derived from Bacillus thuringiensis ssp. kurstaki, a common soil bacterium.    Molecular Characterisation:  Appropriate analysis of the integration site including flanking sequences and bioinformatics analyses have been performed to analyse the construct integrated in the GM plant. Updated bioinformatics analyses revealed that one ORF shared sequence similarity to a putative HECT-ubiquitin ligase protein.   The VKM GMO Panel found no safety implications from the interruption of this gene sequence. Analyses of leaf, grains, whole plant tissue and pollen from the maize MON810 demonstrated that the Cry1Ab protein is expressed at very low levels in all tissues tested and constitute less than 0.001% of the fresh weight in each tissue. The cry1Ab gene is the only transgene expressed in line MON810 and is expressed the highest in leaves. The stability of the genetic modification has been demonstrated over several generations.  Event MON810 and the physical, chemical and functional characteristics of the proteins have previously been evaluated by The VKM Panel on Genetically Modified Organisms, and considered satisfactory (VKM 2007a,b).  Comparative Assessment:  Compositional assessments were performed using the principles and analytes outlined in the OECD consensus document for maize composition (OECD 2002). For maize MON810 grain and forage, VKM previously concluded, based on data from risk assessments and field trials as presented in notification MON810 (C/F/95/12/02) and application NK603 x MON810 (EFA/GMO/UK/2004/1), MON 863 x MON810 (EFSA/GMO/DE/2004/03), MON863xMON810x NK603 (EFSA/GMO/BE/2004/07) and MON 88017 x MON810 (EFSA/GMO/ CZ/2006/33), that maize MON810 is compositionally similar to the non-GM counterparts and conventional maize varieties, except for the new trait (VKM 2005a,b,c, 2007a,b,c).  Comparative analyses of data from field trials located at representative sites and environments in the USA and Europe indicate that maize MON810 is agronomically and phenotypically equivalent to the conventional counterpart and commercially available reference varieties, with the exception of the lepidopteran-protection trait, conferred by the expression of the Cry1Ab protein. The field evaluations support a conclusion of no phenotypic changes indicative of increased plant weed/pest potential of MON810 compared to conventional maize. Evaluations of ecological interactions between maize MON810 and the biotic and abiotic environment indicate no unintended effects of the introduced trait on agronomic and phenotypic characteristics.   Food and Feed Safety Assessment:  Based on current knowledge, there is no reason to assume that the characteristics of processed products derived from maize MON810 would be different from processed products derived from nonGM maize. The compositional and nutritional equivalence of MON810 to conventional non-GM maize varieties is supported by several animal studies.  Acute oral toxicity tests have not indicated any toxicity related to the Cry1Ab protein from Bacillus thuringiensis. Cry1Ab is readily degraded in simulated gastric fluids and no adverse health effects have been reported related to maize MON810 from whole food feeding studies performed on rats, broilers, pigs or dairy cows. Some studies on Atlantic salmon have however indicated possible immunological reactions related to MON810 in fish feed. Bioinformatics analyses show no resemblance of the Cry1Ab protein to known toxins or allergens. Cry1Ab has not been shown to cause IgE mediated allergic reactions and is considered a non-allergenic by EFSA. Some studies have however indicated a potential role of Cryproteins as adjuvants in allergic reactions (VKM 2012b).   Environmental Risk:  There are no reports of the target lepidopteran species attaining pest status on maize in Norway. Since there are no Bt-based insecticides approved for use in Norway, and lepidopteran pests have not been registered in maize, issues related to resistance evolution in target pests are not relevant at present for Norwegian agriculture.  Published scientific studies show no or negligible adverse effects of Cry1Ab protein on non-target arthropods that live on or in the vicinity of maize plants. Cultivation of maize MON810 is not considered to represent a threat to the prevalence of red-listed species in Norway.  Few studies have been published examining potential effects of Cry1Ab toxin on ecosystems in soil, mineralization, nutrient turnover and soil communities. Some field studies have indicated that root exudates and decaying plant material containing Cry proteins may affect population size and activity of rhizosphere organisms (soil protozoa and microorganisms). Most studies conclude that effects on soil microorganisms and microbial communities are transient and minor compared to e