Novel food information: Insect resistant MON 95275 maize

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Background

Health Canada has notified Bayer CropScience Inc., that it has no objection to the food use of insect resistance maize line MON 95275 (hereafter referred to as MON 95275). The company indicated that MON 95275 will not be offered for commercial use as a stand-alone product but will likely be combined through conventional breeding with other approved varieties to provide protection against both above-ground and below-ground maize pests, as well as tolerance to herbicides for effective weed control.

The Department conducted a comprehensive safety assessment of this maize line according to its Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based upon internationally accepted principles for establishing the safety of foods with novel traits. The following provides a summary of the notification from Bayer CropScience Inc. and the evaluation by Health Canada. This document contains no confidential business information.

Introduction

Bayer CropScience Inc. has developed a genetically modified (GM) maize line (Zea mays L.), MON 95275, that exhibits resistance toward various maize rootworm pests (i.e., Diabrotica ssp., Coleoptera; Chrysomelidae). The insect resistance trait was achieved through expression of the novel Mpp75Aa1.1 and the novel Vpb4Da2 insecticidal proteins as well as the DvSnf7.1 double-stranded RNA (dsRNA).

The DvSnf7.1 dsRNA allows an RNAi-mediated gene suppression mechanism toward the snf7 gene sequence of western corn rootworm. This dsRNA is consumed by Diabrotica virgifera virgifera and is recognized by the corn rootworm's natural RNA interference (RNAi) machinery, which results in down regulation of the targeted Diabrotica's snf7 gene leading to mortality.

Recently, a revised nomenclature system for bacterial pesticidal proteins took placed, which reclassified the previously known Cry75Aa1.1 and Vip4Da2 proteins as Mpp75Aa1.1 and Vpb4Da2, respectively. Despite those nomenclature revisions, Mpp75Aa1.1 and Vpb4Da2 proteins follow the same general mode of action steps as other Bacillus thuringiensis insecticidal proteins currently in commercial use for crop protection from insect.

The safety assessment performed by the Food and Nutrition Directorate evaluators was conducted according to Health Canada's Guidelines for the Safety Assessment of Novel Foods. These Guidelines are based on harmonization efforts with other regulatory authorities and reflect international guidance documents in this area (e.g., Codex Alimentarius). The assessment considered: how insect resistant maize MON 95275 was developed, how the composition and nutritional safety of this variety compared to its unmodified comparator, and what the potential is for this variety to present a toxic or allergenic concern. Bayer CropScience Inc. has provided data to support that this variety is safe for use as food in Canada.

The Food and Nutrition Directorate has a legislated responsibility for the pre-market assessment of novel foods and novel food ingredients, as detailed in Division 28 of Part B of the Food and Drug Regulations (Novel Foods). Insect resistant maize MON 95275 is considered to be a novel food under the following part of the definition of novel foods: "c) a food that is derived from a plant, animal, or microorganism that has been genetically modified such that

  1. the plant, animal or microorganism exhibits characteristics that were not previously observed in that plant, animal or microorganism".

Development of the modified plant

MON 95275 was developed by Agrobacterium-mediated transformation of LH244 immature maize embryos using the transformation vector PV-ZMIR525664, which contains a single T-DNA that encompasses four expression cassettes. One cassette resulted in the expression of DvSnf7.1 dsRNA (two dvSnf7.1 complementary inverted repeat sequences) conferring resistance to western maize rootworm (Diabrotica virgifera virgifera). Two gene expression cassettes were introduced resulting in the expression of the insecticidal Mpp75Aa1.1 and Vpb4Da2 proteins, respectively. The expression of the Mpp75Aa1.1 and Vpb4Da2 proteins confer insecticidal resistance to Diabrotica ssp., Coleoptera, and Chrysomelidae maize pests. Finally, the fourth expression cassette results in the expression of CP4 EPSPS, which was used as a selection marker during development, but was excised from the final MON 95275.

Following successful transformation, R0 plants were self-pollinated to generate R1 seeds, which were screened for the presence of T-DNA and absence of vector backbone sequences by means of PCR assay. R1 plants were self-pollinated to generate homozygous positive R2 plants, which were crossed with a Cre recombinase expressing line (LH244 Cre line) to excise the cp4 epsps selection marker from the integration site, resulting in F1 plants. The development of the Cre line involved a transformation step with vector PV-ZMOO513642, which contains its own selection marker (i.e., nptII gene).

The PV-ZMOO513642 vector was then removed from the progenies through conventional breeding yielding F2, F3, F4, F5, and F6 plants, which were free of cp4 epsps, cre genes, and plasmid backbone sequences. The genotype was confirmed in F4 plants by means of Next-Generation Sequencing (NGS) and PCR assays. F4 plants were then crossed via conventional breeding techniques to a Bayer proprietary elite inbred parent (HCL617) to produce hemizygous F4F1 seeds. Finally, a series of self-pollination was performed to produce F4F2, F4F3, F4F4, F5, F5F1, and F6 generation plants. F4, F4F1, F5, F5F1, and F6 plants were used for the molecular characterization of MON 95275, the segregation analysis was performed on F4F2, F4F3, F4F4 generation plants, and F6 generation will be used for commercial development.

The coding sequences for the Vpb4Da2 protein was synthetically synthesized and represent a codon-optimized version of the wild-type sequence found in Bacillus thuringiensis. The coding sequence for the Mpp75Aa1.1 was synthetically synthesized and represent a codon-optimized version of the full-length precursor form of the insecticidal protein Mpp75Aa1 from Brevibacillus laterosporus (formally identified as Bacillus laterosporus), where the native membrane-transiting signal peptide has been removed. As synthetic DNA was used for these coding sequences, it is not anticipated that other genes from B. laterosporus or B. thuringensis be carried over into MON 95275 genome.

The Mpp75Aa1.1 and Vpb4Da2 insecticidal proteins have not previously been assessed by Health Canada.

The DvSnf7.1 dsRNA was designed to be partially complementary to the WCR's snf gene, coding a specific portion of the WCR Snf7 subunit protein. The double inverted repeat sequences that form the active portion of the DvSnf7.1 dsRNA are identical to those in dvSnf7 suppression cassette introduced in MON 87411, which is a maize variety assessed and approved by Health Canada. Both dvSnf7.1 and dvSnf7 suppression cassettes share the same functional sequences, but dvSnf7.1 have a different leader sequence in order to increase expression efficacy. The safety of dvSnf7.1 leader sequence was assessed by bioinformatic analysis, which will be discussed below.

The petitioner provided information to support the safety and historical use of each donor organism and the recipient organism (i.e., the public elite inbred transformable maize line LH244). None of these organisms pose a health or safety concern.

Characterization of the modified plant

Next Generation Sequencing (NGS) was used to assess the insert copy number of the T-DNA and characterize the junction sequences in five generations (F4, F4F1, F5, F5F1, and F6) of MON 95275. Additionally, sequencing of specific PCR amplicons from the inserted DNA was used to determine the T-DNA intactness as well as integration site and flanking genomic sequences.

With regards to the NGS quality metrics, the company reported a minimal depth coverage of 75 X for each sequenced plant, which has been reported to be adequate for providing comprehensive coverage and detection of all inserted DNA as well as potential unintended inserted fragments. The nativeFootnote 1, which is present in a single copy locus in maize, was used by the petitioner to estimate the depth coverage in both the conventional (LH244) control and MON 95275. The company also reported complete genome coverage. The breadth of coverage was determined by identifying all single native copy genes throughout the maize reference genome (yielding hundreds) before randomly selecting two of those per chromosome. Then, the company fully mapped these two random single copy maize genes from each maize chromosomes in both conventional control and MON 95275 (F4 generation) providing a proper indication of the breadth of coverage.

The molecular characterization demonstrated a single T-DNA insertion in chromosome 3 of MON 95275. The junction sequences were demonstrated to be linked by contiguous, known, and expected DNA sequences, demonstrating proper orientation of the T-DNA within MON 95275 genome. The sequencing data confirmed that the T-DNA integration occurred in a non-coding region of the genome and did not disrupt endogenous genetic elements.

NGS was also used to confirm the absence of vector backbone sequences and the excision of the cp4-epsps selection maker in five generations (F4, F4F1, F5, F5F1, and F6) of MON 95275. The NGS data confirmed excision of the cp4-epsps selection maker, which was replaced by a single loxP site as expected within the MON 95275 genome. The NGS data also demonstrated the absence of any PV-ZMIR525664 or PV-ZMOO513642 vector backbone sequences, including the absence of the nptII gene.

The integrated T-DNA exhibits Right and Left Border termini deletions, which often occur in Agrobacterium-mediated transformation. A 6 bp co-insertion within the genomic 3' flanking region, and a single nucleotide difference within an intervening sequence were also identified. Further, a 746 bp deletion was found in the genomic DNA at the T-DNA insertion site. These deletions within T-DNA insert sequence and the genomic DNA were attributed to double-stranded break repair mechanisms in the plant during the Agrobacterium-mediated transformation process. The petitioner's open-reading frame (ORF) analysis demonstrates that these deletions do not result in any putative ORFs with similarity to known toxins or allergens.

Bioinformatics analyses of putative ORFs (defined as any sequence from stop-to-stop codons) in all six reading frames were performed on both the sequenced T-DNA I insertion site and junction sequences for similarity to known and putative allergens and toxins. Putative sequenced proteins were searched against the AD_2021, the Uniprot toxin protein database (TOX_2021), and the GenBank protein database (PRT_2021). No biologically relevant alignments were found for MON 95275.

Genetic stability of the T-DNA insert in the MON 95275 genome was demonstrated by assessing individual MON 95275 plants from five generations (F4, F4F1, F5, F5F1, and F6) by means of NGS. The results indicate that the T-DNA insert is intact and stable over all five generations of MON 95275. PCR analysis was performed on 3 generations (F4F2, F4F3, and F4F4) and demonstrated that MON 95275 T-DNA insert segregated in accordance with the Mendelian principles of inheritance for a single genetic locus.

Product information

MON 95275 differs from its traditional counterparts by the expression of Mpp75Aa1.1 and Vpb4Da2 insecticidal proteins as well as the DvSnf7.1 dsRNA. These insecticidal proteins and dsRNA levels were determined at different growth phase in various plant tissues by means of validated enzyme-linked immunosorbent assay (ELISA) and QuantiGene® Plex 2.0 Assay, respectively, through a multi-site field trial using a randomized complete block (RCB) design. Five sites representative of common maize-producing regions located in the U.S.A. were used with four blocks at each site, resulting in a total of 20 samples per tissue tested for each given notified substance.

At R1 phase, silks contain the highest level of Vpb4Da2 and Mpp75Aa1.1 proteins while leaves and roots contain the highest level of DvSnf7.1 dsRNA. At maturity, the average levels of Vpb4Da2 protein, Mpp75Aa1.1 protein, and DvSnf7.1 dsRNA in grains were 1.2±0.086, 1.3±0.086, and 0.28x10-3±0.021x10-3 μg/g of tissue dry weight, respectively.

The notified full-length Mpp75Aa1.1 protein encoded by the mpp75Aa1.1 gene is 295 amino acids in length and has a molecular weight of approximately 35.2 kDa. The notified Vpb4Da2 full-length protein encoded by the vpb4Da2 gene is 937 amino acids in length and has a molecular weight of approximately 104.9 kDa.

To assess the safety of both insecticidal proteins, recombinant Vpb4Da2 and Mpp75Aa1.1 proteins were expressed in a microbial expression system and used as surrogates for MON 95275 expressed proteins. Equivalence between microbially-produced and MON 95275 proteins were established using SDS-PAGE, western blot, protein glycosylation, N-terminal sequence/mass fingerprint analysis using LC-MS/MS, and an insect bioassay against WCR larvae. The results of these analyses conclude that microbially-produced proteins are equivalent to their full-length plant-produced counterpart in MON 95275, and therefore can be used as test articles for protein safety studies.

The full-length DvSnf7.1 dsRNA exhibits a size of approximately 1.4 kb and has a length of 1014 bp. Northern blot analysis revealed three major readthrough transcript isoforms distinguishable by their splicing level relative to the neighbor native genomic gene adjacent to the 3' end of the insertion site. The safety of those unexpected readthrough isoforms was addressed by ranking the positioning of each start codon downstream of the dvSnf7.1 double inverted sequences and by evaluating the similarity of all putative sequences revealed through means of the ORF analysis against known allergens and toxins. All identified ORFs exhibited start codons in poor contexts of translation and no biologically relevant alignments were found.

Instead of using the DvSnf7.1 dsRNA (1014 bp) to perform toxicological studies, the company used an in vitro synthesized DvSnf7 dsRNA (968 bp) notified in the previously assessed MON 87411 maize eventFootnote 2. To do so, the company established equivalency between the MON 95275-derived DvSnf7.1 dsRNA (including readthroughs) and the in vitro synthesized DvSnf7.1 dsRNA by means of sequencing their retrotranscribed cDNA, RNase If degradation followed by Northern blot, and LC50 assay against Southern Corn Rootworm (SCR) larvaeFootnote 3. Second, the company established the equivalency between the MON 87411-derived DvSnf7 dsRNA and the in vitro synthesized DvSnf7 dsRNA by means of LC50 assay against SCR larvae and RNase If degradation followed by Northern blot. Thirdly, the same assays were performed on both the in vitro DvSnf7.1 and the in vitro DvSnf7 dsRNA, which showed no significant difference between the LC50 values and confirm the presence of the active double stranded 240-bp region in both dsRNA. Based on this three-step rationale and comparative data, the Bureau of Microbial Hazards concluded that the MON 95275-derived DvSnf7.1 dsRNA is equivalent to the in vitro synthesized DvSnf7 dsRNA (968 bp) notified in the previously assessed MON 87411.

Based on the information provided, there are no concerns regarding the food use of MON 95275 maize from a molecular perspective.

Dietary exposure

It is expected that MON 95275 maize will be used in applications similar to conventional maize varieties. The petitioner does not anticipate a significant change in the food use of maize with the introduction of MON 95275 maize.

Nutrition

The petitioner provided compositional data for genetically modified corn MON 95275 and genetically similar conventional control (non-GM LH244+HCL617) obtained from grain samples harvested from five field trials conducted in the US during the 2019 growing season. Each field trial was planted with four replicates of each of the modified and conventional corn in a randomized complete block design.

Samples were analyzed using acceptable methods for proximates, fibres, amino acids, fatty acids, minerals, vitamins and anti-nutrients. The data provided was for all key nutrients and anti-nutrients as described in the Organization for Economic Co-Operation and Development "Consensus Document on Compositional Considerations for New Varieties of Maize (Zea Mays): Key Food and Feed Nutrients, Anti-nutrients and Secondary Plant Metabolites" (2002).

Where a statistically significant difference (P-value < 0.05) was identified between the modified corn and its conventional control, the nutritional relevance of the difference was determined through comparison to the control range value (maximum value minus the minimum value) of the conventional control and the natural variability defined by the range of values observed in the literature and reported in the Agriculture and Food Systems Institute's Crop Composition Database for corn.

There were no statistically significant differences between MON 95275 corn and the conventional control for 54 of the 61 components analyzed in grain. For the seven components (palmitic acid, stearic acid, oleic acid, linoleic acid, arachidic acid, calcium and vitamin B6) that showed a statistically significant, mean differences between MON 95275 and the conventional control were less than the corresponding control range values, suggesting that the genetic modification does not impact levels of these components more than the natural variation observed within the conventional control grown at multiple locations.

Therefore, the Bureau of Nutritional Sciences has not identified any nutritional concerns related to food use MON 95275 corn.

Chemistry

Chemical contaminant residue data have not been provided, nor have any unique contaminant considerations been identified with respect to MON 95275 maize. As well, there are no maximum levels for contaminants specific to this food set out in Health Canada's List of Contaminants and Other Adulterating Substances in Foods or in the List of Maximum Levels for Chemical Contaminants in Foods.

As with any food or food ingredient sold in Canada, it is the responsibility of the food manufacturer to ensure that its use does not result in a violation of Section 4(1)(a) and (d) of the Food and Drugs Act, which states that no person shall sell an article of food that has in or on it any poisonous or harmful substance or is adulterated. If an elevated concentration of any chemical contaminant is found in any type of food, the Bureau of Chemical Safety may conduct a human health risk assessment to determine if there is a potential safety concern and whether risk management measures are required.

Toxicology

The Pre-Market Toxicology Assessment Section (PTAS) evaluated the safety of MON 95275 maize by assessing the potential toxicity of the insecticidal proteins Mpp75Aa1.1 and Vpb4Da2 and the insecticidal DvSnf7.1 dsRNA.

The insect resistance traits are not expected to change the overall consumption pattern of maize in Canada, because these traits would not be apparent to consumers and do not lead to new food products being created.

Activation of Mpp75Aa1.1 and Vpb4Da2 proteins, and subsequent binding of the core regions to specific insect receptors involves molecular machinery specifically present in the insect midgut, and therefore PTAS considers that the potential risks to humans and other vertebrates exposed to the protein are expected to be minimal. Similarly, the DvSnf7.1 dsRNA was designed to match the snf7 gene of Western Corn Rootworm (WCR) and specifically suppress the expression of this insect gene through an RNA interference (RNAi) mode of action, and it is not expected to present a hazard to humans.

To support the toxicological safety of the Mpp75Aa1.1 and Vpb4Da2 proteins, the petitioner provided the results of acute oral toxicity studies in mice, conducted in compliance with the U.S. Environmental Protection Agency (EPA) Good Laboratory Practice (GLP) requirements and with EPA Health Effects Testing Guideline OPPTS 870.1100. The test material was purified Mpp75Aa1.1 or Vpb4Da2 protein produced in an Escherichia coli-based expression system. The Bureau of Microbial Hazards (BMH) confirmed that the E. coli-produced proteins were equivalent from a safety perspective to those expressed in MON 95275 maize, and therefore that they were an appropriate surrogate test material for studying the safety of the Mpp75Aa1.1 and Vpb4Da2 proteins produced in planta.

Neither Mpp75Aa1.1 protein nor Vpb4Da2 protein produced any apparent signs of acute toxicity in mice, at doses of 2000 mg/kg bw and 5000 mg/kg bw, respectively. The No Observed Adverse Effect Level (NOAEL) for Mpp75Aa1.1 protein and Vpb4Da2 protein was 2000 mg/kg bw per day and 5000 mg/kg bw per day, respectively.

The toxicological safety of Mpp75Aa1.1 and Vpb4Da2 proteins was further assessed by comparing the amino acid (aa) homology of these proteins to known protein toxins. Mpp75Aa1.1 protein shared 25.9% homology to epsilon-toxin type B (ETXB) from Clostridium perfringens and Vpb4Da2 protein was 32.7% homologous to the Protective Antigen (PA) from Bacillus anthracis. Although there is no accepted consensus threshold for aa homology to known toxins, PTAS considers that overall homologies of 25.9% and 32.7% are not suggestive of a high degree of similarity that could be a concern to human health, especially since these homologies were only to regions that are highly conserved across the respective protein families and are not involved in mediating toxicity. Overall, the bioinformatic evidence suggests that neither Mpp75Aa1.1 nor Vpb4Da2 is likely to behave as a toxin.

The petitioner provided estimates of the dietary intake of Mpp75Aa1.1 and Vpb4Da2 proteins that would result from consumption of MON 95275 maize. The margin of exposure (MOE) between the NOAEL for Mpp75Aa1.1 protein (2000 mg/kg bw per day) and the estimated exposure to Mpp75Aa1.1 protein in the general population (2.2 μg/kg bw per day) is 9.0 x 105. Similarly, the MOE between the NOAEL for Vpb4Da2 protein (5000 mg/kg bw per day) and the estimated exposure to Vpb4Da2 protein in the general population (2.0 μg/kg bw per day) was 2.5 x 106. Because these estimates considered consumers only, were based on 90th percentiles for maize product consumption, assumed that all maize products consumed were derived from MON 95275, and that there is no reduction in the levels of Mpp75Aa1.1 and Vpb4Da2 proteins due to cooking or processing (which is not likely to be the case), PTAS considers that the MOEs are protective of human health.

The DvSnf7.1 dsRNA transcript expressed by MON 95275 maize was deemed by BMH to be equivalent to the DvSnf7 dsRNA molecule expressed by the previously approved crop MON 87411 maize, suggesting that this expressed RNA is already present in the Canadian food supply. There have been no reports of adverse effects arising from consumption of foods derived from MON 87411 maize.

The safety of the DvSnf7 dsRNA transcript in the approved MON 87411 maize was supported by a 28-day oral toxicity study in mice, which was previously reviewed by PTAS. This study was conducted in compliance with the principles of GLP, and according to OECD Testing Guideline 407. There were no adverse effects and the NOAEL from this study was 100 mg/kg bw per day. Since BMH confirmed that the respective RNA transcripts in MON 87411 and MON 95275 are equivalent, the NOAEL of 100 mg/kg bw per day can be applied to DvSnf7.1 dsRNA from MON 95275 by the principle of read-across.

There is no evidence to suggest that the DvSnf7.1 dsRNA expressed by MON 95275 is translated into proteins, since the secondary structure produced by the internal inverted repeat sequence tends to interfere with translation. The aa sequences of potential proteins encoded by DvSnf7.1 dsRNA demonstrated no significant homology to any known toxins.

The DvSnf7.1 dsRNA transcript sequence involved in the RNAi mode of action did not demonstrate any significant homologies to either human RNA sequences or RNA sequences of other off-target organisms. Therefore, the DvSnf7.1 dsRNA is very unlikely to have off-target binding and gene-suppressive effects.

The MOE between the 28-day NOAEL for DvSnf7.1 dsRNA (100 mg/kg bw per day) and the estimated exposure to DvSnf7.1 dsRNA in the general population (0.0005 μg/kg bw per day) is 2.0 x 108. PTAS considers this MOE to be protective of safety. Furthermore, it is considered to be an underestimate since levels of the DvSnf7.1 dsRNA in MON 95275 maize are expected to be reduced by processing and cooking and ingested dietary RNA is generally degraded by nucleases in saliva, acidic conditions in the stomach, and additional digestive enzymes in the small intestine. In addition, there is a physical barrier (i.e., mucus and cellular membranes) that limits the uptake of dietary RNA by gastrointestinal cells. Therefore, of the estimated dietary dsRNA DvSnf7.1 intake, only a very small fraction is expected to be absorbed after oral ingestion.

Based on the available information, the PTAS did not identify any toxicological food safety concerns with the use of the MON 95275 maize, as proposed.

Allergenicity

Maize (Z. mays) is not considered a common allergenic food (OECD, 2002Footnote 4) and is not on Health Canada's list of priority food allergens. The respective donor organisms for the mpp75Aa1.1 and vpb4Da2 genes are also widespread in prevalence and not known sources of allergens.

To support the allergenic safety of MON 95275 maize-produced Mpp75Aa1.1 and Vpb4Da2 proteins, the petitioner provided the results of aa homology searches to known allergens, as well as in vitro simulated digestibility studies, and thermostability studies.

The aa sequences of the Mpp75Aa1.1 and Vpb4Da2 proteins were queried against the COMprehensive Protein Allergen Resource (COMPARE) database of the Health and Environmental Sciences Institute (HESI). Specifically, the following comparisons were performed: (1) full-length aa sequence alignment, to assess overall homology; (2) 80-aa sliding window alignment, to assess structural homology; and (3) 8-aa identity match searches to assess homology to potential immunoglobulin E (IgE) epitopes. According to Codex Alimentarius, proteins which share full-length or 80-aa sliding window homologies greater than 35%, or 8-aa exact matches, with known food allergens may signify a risk of cross-reaction. Neither Mpp75Aa1.1 nor Vpb4Da2 protein shared any full-length or 80-aa sliding window homologies above 35% or any 8-aa exact matches to any allergens in the COMPARE database. These findings suggest that the Mpp75Aa1.1 and Vpb4Da2 proteins are unlikely to cross-react with known food allergens when ingested in MON 95275 maize.

There is an association between the resistance of dietary proteins to gastrointestinal digestion and their likelihood of triggering an allergy. The susceptibility of the MON 95275-produced Mpp75Aa1.1 protein and Vpb4Da2 protein to digestion under conditions representative of the human gastrointestinal tract (GIT) was assessed by subjecting equivalent proteins (i.e., E. coli-produced Mpp75Aa1.1 and Vpb4Da2) to simulated gastric fluid and simulated intestinal fluid assays in vitro. Both Mpp75Aa1.1 and Vpb4Da2 proteins were completely degraded within the first 10 minutes of incubation in simulated gastric fluid, containing pepsin, and within 2 hours of incubation in simulated intestinal fluid (containing pancreatin). Following ingestion of food products derived from MON 95275 maize, both Mpp75Aa1.1 and Vpb4Da2 proteins are expected to be rapidly and completely digested. PTAS concludes that peptides from Mpp75Aa1.1 or Vpb4Da2 proteins would be unlikely to persist long enough in the digestive tract to interact with the immune system and trigger an allergic response.

Thermostability studies showed that Mpp75Aa1.1 and Vpb4Da2 proteins lose both structural and functional activity when heated at temperatures above 55°C for more than 15 minutes. Since normal processing and cooking conditions of maize food products involve heating, it is expected that Mpp75Aa1.1 and Vpb4Da2 would be denatured and inactivated prior to consumption. Therefore, Mpp75Aa1.1 and Vpb4Da2 proteins are not expected to behave as allergens when ingested in MON 95275 maize.

Almost all food allergens are proteins. The DvSnf7.1 dsRNA expressed by MON 95275 is not a protein and is very unlikely to be translated into a protein. The aa sequences of potential proteins encoded by DvSnf7.1 dsRNA were queried against the COMPARE allergen database. There were no full-length or 80-aa sliding window homologies above 35% and no 8-aa exact peptide matches, for any of the hypothetical proteins and peptides. This suggests that, even if the DvSnf7.1 dsRNA were to be translated into a protein and consumed in MON 95275 maize, it is very unlikely that the resultant protein would behave as an allergen.

The PTAS has determined that the notified MON 95275 maize is not expected to pose any additional allergenic safety concerns for consumers compared to conventional maize.

Conclusion

Health Canada's review of the information presented in support of the use of insect resistant maize variety MON 95275 does not raise concerns related to food safety.

Health Canada's opinion refers only to the food use of MON 95275 maize. Issues related to its use as animal feed have been addressed separately through existing regulatory processes in the Canadian Food Inspection Agency.

This Novel Food Information document has been prepared to summarize the opinion regarding the subject product provided by the Food and Nutrition Directorate, Health Products and Food Branch, Health Canada. This opinion is based upon the comprehensive review of information submitted by the petitioner according to the Guidelines for the Safety Assessment of Novel Foods.

For further information, please contact:

Health Canada
Novel Food Section
Food and Nutrition Directorate
Health Products and Food Branch
251 Sir Frederick Banting Driveway
PL2204E
Ottawa, Ontario, K1A 0K9

Email: bmh-bdm@hc-sc.gc.ca

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