Decision Document DD2014-104
Determination of the Safety of Monsanto Canada Inc. Cotton (Gossypium hirsutum) Event 88701

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June 26, 2014

This Decision Document has been prepared to explain the regulatory decisions reached under Section 2.6 Guidelines for the Assessment of Novel Feeds: Plant Sources, of Chapter 2 of the RG-1 Regulatory Guidance: Feed Registration Procedures and Labelling Standards, and based on the environmental criteria in Directive 94-08 Assessment Criteria for Determining Environmental Safety of Plants with Novel Traits.

The Canadian Food Inspection Agency (CFIA), specifically the Animal Feed Division of the Animal Health Directorate, with input from the Plant and Biotechnology Risk Assessment Unit of the Plant Health Science Directorate, CFIA, has evaluated information submitted by Monsanto Canada Inc. This information is in regard to the herbicide tolerant cotton event MON 88701. The CFIA has determined that feed derived from these modified plants does not present a significant risk to the environment, nor does it present livestock feed safety concerns when compared to currently commercialized cotton varieties in Canada.

Taking into account this evaluation, use as livestock feed of cotton event MON 88701 is, therefore, authorized by the Animal Feed Division of the Animal Health Directorate as of June 26, 2014. Any cotton lines derived from cotton event MON 88701 may also be used as livestock feed, provided that (i) no inter-specific crosses are performed; (ii) the intended uses are similar; (iii) it is known based on characterization that these plants do not display any additional novel traits and are substantially equivalent to cotton varieties that are currently grown and permitted to be used as livestock feed in Canada, in terms of their potential environmental impact and livestock feed safety; and (iv) the novel genes are expressed at a level similar to that of the authorized line.

Cotton event MON 88701 is subject to the same phytosanitary import requirements as the unmodified cotton varieties, and is required to meet the requirements of other Canadian legislation including, but not limited to, the Food and Drugs Act and the Pest Control Products Act.

Please note that the livestock feed safety of novel feeds is a critical step in the potential commercialization of these plant types. Other requirements, such as the evaluation of food safety by Health Canada, have been addressed separately from this review.

Table of Contents

  1. Brief Identification of the Modified Plant
  2. Background Information
  3. Description of the Novel Traits
    1. Development Method
    2. Tolerance to Dicamba
    3. Tolerance to Glufosinate-Ammonium
    4. Stable Integration into the Plant Genome
  4. Criteria for the Environmental Assessment
    1. Potential for Cotton Event MON 88701 to Become a Weed of Agriculture or be Invasive of Natural Habitats
    2. Potential for Gene Flow from Cotton Event MON 88701 to Sexually Compatible Plants Whose Hybrid Offspring May Become More Weedy or More Invasive
    3. Altered Plant Pest Potential of Cotton Event MON 88701
    4. Potential Impact of Cotton Event MON 88701 on Non-Target Organisms
    5. Potential Impact of Cotton Event MON 88701 on Biodiversity
  5. Criteria for the Livestock Feed Assessment
    1. Potential Impact of Cotton Event MON 88701 on Livestock Nutrition
    2. Potential Impact of Cotton Event MON 88701 on Animal Health and Human Safety as it Relates to the Potential Transfer of Residues into Foods of Animal Origin and Worker/Bystander Exposure to the Feed
  6. New Information Requirements
  7. Regulatory Decision

I. Brief Identification of the Modified Plant

Designation of the Modified Plant: Cotton Event MON 88701, OECD Unique Identifier MON-887Ø1-3

Applicant: Monsanto Canada Inc.

Plant Species: Cotton (Gossypium hirsutum)

Novel Traits: Tolerance to dicamba and glufosinate-ammonium herbicides

Trait Introduction Method: Agrobacterium-mediated transformation

Intended Use of the Modified Plant: Production of cotton for fibre, whole or crushed cottonseed and cottonseed meal (cake, grain, flakes, pellets) or roughage for livestock feed and cottonseed oil for human consumption. These materials will be grown outside Canada, in the usual production areas for cotton. Cottonseed and cottonseed meal will be imported into Canada for livestock feed use only.

II. Background Information

Monsanto Canada Inc. has developed a cotton event that is tolerant to dicamba (3,6-dichloro-2-methoxybenzoic acid) and glufosinate-ammonium herbicides. Cotton event MON 88701 was developed by Monsanto Canada Inc. using recombinant deoxyribonucleic acid (DNA) technology, resulting in the introduction of the demethylase gene and the bialaphos resistance (bar) gene. The demethylase gene is derived from Stenotrophomonas maltophilia and encodes a dicamba monooxygenase (DMO) enzyme. This enzyme rapidly demethylates dicamba to metabolite 3,6-dichlorosalicylic acid (DCSA). The bar gene is derived from the soil bacterium Streptomyces hygroscopicus and encodes a phosphinothricin N-acetyltransferase (PAT) enzyme. This enzyme inactivates the herbicide glufosinate-ammonium.

Monsanto Canada Inc. has provided information on the identity of cotton event MON 88701, a detailed description of the transformation method and information on the genes' insertion sites, copy number, levels of expression in the plant, and the roles of the inserted genes and regulatory sequences. The novel proteins were identified and characterized. Information was provided for the evaluation of the potential toxicity of the novel proteins to livestock and non-target organisms and potential allergenicity of the novel proteins to humans and to livestock.

Cotton event MON 88701 was field tested at eight sites in the United States (U.S.) in 2010. An unmodified control cotton variety that shares the same genetic background as cotton event MON 88701 was included in the trials to act as a comparator for cotton event MON 88701. Nine conventional control cotton varieties were also included in the field trials to establish a typical cotton behavior reference range for phenotypic parameters.

Nutritional components of cotton event MON 88701 seed and forage, such as protein, fat, moisture, and ash, fibre, amino acids, fatty acids, vitamins, minerals and anti-nutrients were compared to those of the unmodified control cotton variety and to the reference range established by the conventional control cotton varieties.

The Animal Feed Division (AFD) of the Animal Health Directorate, CFIA, with input from the Plant and Biotechnology Risk Assessment Unit of the Plant Health Science Directorate, CFIA, has reviewed the above information. The following assessment criteria, as described in Section 2.6 Guidelines for the Assessment of Novel Feeds: Plant Sources, of Chapter 2 of the RG-1 Regulatory Guidance: Feed Registration Procedures and Labelling Standards and Directive 94-08 Assessment Criteria for Determining Environmental Safety of Plants with Novel Traits were used to determine the safety and efficacy as livestock feed and the environmental safety of this novel feed:

  • the potential impact of cotton event MON 88701 on livestock nutrition;
  • the potential impact of cotton event MON 88701 on animal health and human safety as it relates to the potential transfer of residues into foods of animal origin and worker/bystander exposure to the feed;
  • the potential for cotton event MON 88701 to become a weed of agriculture or be invasive of natural habitats;
  • the potential for gene flow from cotton event MON 88701 to sexually compatible plants whose hybrid offspring may become more weedy or more invasive;
  • the potential for cotton event MON 88701 to become a plant pest;
  • the potential impact of cotton event MON 88701 and its gene products on non-target organisms, including humans; and
  • the potential impact of cotton event MON 88701 on biodiversity.

The AFD has also considered whether feeds derived from cotton event MON 88701 meet the definitions and requirements of feeds as listed in Schedule IV of the Feeds Regulations.

Monsanto Canada Inc. has provided the CFIA with a method for the detection and identification of cotton event MON 88701.

III. Description of the Novel Traits

1. Development Method

Cotton event MON 88701 was developed through Agrobacterium-mediated transformation of hypocotyls and contains the demethylase gene and the bialaphos2 resistance (bar) gene of S. maltophilia and S. hygroscopicus respectively, and associated regulatory elements. Transformed cells were selected on the basis of tolerance to glufosinate-ammonium and regenerated to produce plants. Cotton event MON 88701 was identified as a successful transformant based on molecular analyses, herbicide efficacy and agronomic evaluations, and was thus chosen for further development.

2. Tolerance to Dicamba

Dicamba is a group 4 herbicide that mimics indole-3-acetic acid, a natural plant hormone of the auxin class. Dicamba application causes rapid and uncontrolled growth of the stems, petioles and leaves of sensitive plants. This leads to uncontrolled cell division and growth, resulting in the destruction of vascular tissue and eventually plant death. Dicamba is used for broadleaf weed control on grain crops, pastures and non-crop areas.

Cotton event MON 88701 contains a dmo expression cassette that produces a DMO protein to confer tolerance to dicamba herbicide. The DMO protein is an enzyme classified as a monooxygenase and catalyzes the demethylation of dicamba to the non-herbicidal compound DCSA and formaldehyde. The active form of DMO is a Rieske-type non-heme iron oxygenase, that forms part of a three-component system comprised of a reductase, a ferredoxin and a terminal oxygenase. These three proteins work together in a redox system similar to many other oxygenases to transport electrons from NADH to oxygen and catalyze the demethylation of an electron acceptor substrate, in this case, dicamba. The formation of a trimer is required because the electron transport that culminates in the demethylation of dicamba occurs from one monomer to another in the native conformation of the enzyme

3. Tolerance to Glufosinate-Ammonium

The PAT (bar) protein produced in cotton event MON 88701 is an enzyme classified as an acetyltransferase that acetylates glufosinate to produce non-herbicidal N-acetyl glufosinate. Glufosinate is a racemic mixture of the D- and L- forms of phosphinothricin. The herbicidal activity of glufosinate results from the binding of L-phosphinothricin to glutamine synthetase. Glutamine synthetase is responsible for the assimilation of ammonia generated during photorespiration. The binding of L-phosphinothricin to glutamine synthetase results in the inactivation of glutamine synthetase and a subsequent toxic build-up of ammonia within the plant, resulting in death.

The PAT protein produced in cotton event MON 88701 is the same as the PAT protein produced in other glufosinate-ammonium-tolerant crops that have already been approved for unconfined release and animal feed use in Canada, including cotton events T304-40 and GHB119 (DD2011-87).

Expression of the DMO and PAT (bar) proteins in cotton event MON 88701 is driven by constitutive promoters. Samples of cotton tissues (leaf, root, pollen and seed) were collected from plants from eight field trials in the U.S. during 2010.

DMO Protein Levels in MON 88701

The mean DMO protein levels in cotton event MON 88701 across the eight sites was as follows: highest in overseason leaf (OSL) 2 and OSL3 at 240 μg/g dwt and lowest in pollen at 14 μg/g fwt, and were 21 μg/g dwt in cotton seed.

PAT (bar) Protein Levels in MON 88701

The mean PAT (bar) protein levels in MON 88701 across the eight sites was highest in cottonseed at 6.6 μg/g dwt and lowest in pollen that expressed <LOQ in all but six samples. The mean PAT (bar) protein levels in six pollen samples from cotton event MON 88701 was 0.56 μg/g fwt.

To obtain sufficient quantities of DMO protein for evaluation of environmental and feed safety, it was necessary to express the demethylase gene in an Escherichia coli (E. coli) production system. Equivalency was demonstrated between the cotton event MON 88701-produced DMO protein and an E. coli-produced DMO protein by comparing their molecular weights, immunoreactivity, glycosylation, N-terminal sequence analysis, MALDI-TOF mass spectrometry and functional activity. Based on the results, the proteins were found to be equivalent. Demonstration of equivalence between the DMO protein produced in E. coli and the DMO protein produced in cotton event MON 88701 allows the DMO protein produced in E. coli to be used in studies to confirm the safety of the DMO protein produced in cotton event MON 88701.

To obtain sufficient quantities of PAT (bar) protein for evaluation of environmental and feed safety, it was necessary to express the pat gene in an E. coli production system. Equivalency was demonstrated between the cotton event MON 88701-produced PAT protein and an E. coli-produced PAT protein by comparing their molecular weights, immunoreactivity, glycosylation, N-terminal sequence analysis, MALDI-TOF mass spectrometry and functional activity. Based on the results, the proteins were found to be equivalent. Demonstration of equivalence between the PAT protein produced in E. coli and the PAT protein produced in cotton event MON 88701 allows the PAT protein produced in E. coli to be used in studies to confirm the safety of the PAT protein produced in cotton event MON 88701.

The potential allergenicity and toxicity of the DMO and PAT (bar) proteins to livestock and non-target organisms were evaluated. The weight of evidence indicates that the DMO and PAT (bar) proteins are unlikely to be allergenic. The source of the demethylase geneand the bar gene is S. maltophilia and S. hygroscopicus respectively, and these are not commonly associated with allergenicity. The DMO and the PAT protein amino acid sequences lack relevant similarities to known allergens. E. coli-produced DMO and PAT proteins were shown experimentally to be rapidly degraded in simulated gastric fluid and not to be heat stable. Cotton event MON 88701 DMA and PAT proteins were shown experimentally to be unglycosylated.

It was also concluded that the DMO and the PAT proteins are unlikely to be toxic to livestock and non-target organisms because they lack a mode of action to suggest that they are intrinsically toxic to livestock or non-target organisms; the DMO and the PAT protein amino acid sequences lack relevant similarities to known toxins and no adverse effects were observed when microbial DMO and PAT proteins were ingested by mice at doses of 283 and 1086 mg/kg-bw respectively.

The demethylase gene is derived from Stenotrophomonas maltophilia and encodes a DMO enzyme. This enzyme rapidly demethylates dicamba to the herbicidally inactive metabolite 3,6-dichlorosalicylic acid (DCSA). The bar gene is derived from the soil bacterium Streptomyces hygroscopicus and encodes a phosphinothricin N-acetyltransferase (PAT) enzyme. This enzyme inactivates the herbicide glufosinate-ammonium.

4. Stable Integration into the Plant Genome

Molecular characterization by Southern blot analysis demonstrated that cotton event MON 88701 contains one intact copy of a gene cassette containing the demethylase gene and the bar gene, each with its regulatory elements, inserted at a single site in the cotton genome. No additional elements were detected in cotton event MON 88701, including intact or partial DNA fragments of the gene cassette or backbone sequences from the plasmid vector, linked or unlinked to the intact insert.

The stability of the insert within cotton event MON 88701 was verified by Southern blot analysis of genomic DNA from the R3 generation and by detection of the DMO and PAT proteins in various tissue samples collected from field trials. The inheritance pattern of the insert and the DMO and PAT protein expression trait across five segregating generations of cotton event MON 88701 showed that the insert segregates according to Mendelian rules of inheritance for a single genetic locus.

IV. Criteria for the Environmental Assessment

Lines derived from cotton event MON 88701 will not be grown in Canada. However, Canada imports cottonseed, as well as a wide range of other cotton products that are used as human food, livestock feed or other industrial products.

1. Potential for Cotton Event MON 88701 to Become a Weed of Agriculture or be Invasive of Natural Habitats

Cotton (Gossypium hirsutum) is a member of the family Malvaceae. It is a perennial species cultivated as an annual and grown in the U.S., mostly in areas from Virginia southward and westward to California. Cotton is not grown in Canada as it is not adapted to environmental conditions found at these latitudes.

Cotton is not considered a weed pest in the regions where it is grown, nor is it invasive of unmanaged habitats in Canada. Cotton event MON 88701 has not been modified to have altered cold-tolerance, and information supplied by Monsanto Canada Inc. indicates that the reproductive and survival biology of cotton event MON 88701 is unchanged compared to its unmodified control.

The CFIA has therefore concluded that cotton event MON 88701 is unlikely to become a weed of agriculture or invasive of natural habitats.

2. Potential for Gene Flow from Cotton Event MON 88701 to Sexually Compatible Plants Whose Hybrid Offspring May Become More Weedy or More Invasive

Cotton is predominately self-pollinated. Although cross-pollination may occur at low levels, particularly in the presence of pollinators such as honeybees, cotton has no wild relatives native to Canada. Wild relatives of commercial cotton, such as Gossypium barbadense and G. tomentosum, are found only in tropical and sub-tropical regions.

This information, together with the fact that the novel traits have no intended effects on cotton reproductive biology, led the CFIA to conclude that gene flow from cotton event MON 88701 to wild relatives in Canada is not possible.

3. Altered Plant Pest Potential of Cotton Event MON 88701

Cotton is not a plant pest in Canada, and the intended effect of the novel traits is unrelated to plant pest potential. In addition, agronomic characteristics of cotton event MON 88701 are similar to those described for currently commercialized cotton varieties.

The CFIA has therefore determined that cotton event MON 88701 does not present a plant pest concern.

4. Potential Impact of Cotton Event MON 88701 on Non-Target Organisms

The dicamba and glufosinate-ammonium herbicide tolerance traits introduced into cotton event MON 88701 are unrelated to a potential impact on non-target organisms. In addition, DMO and PAT proteins naturally occur in plant and microbial-based foods that have a history of safe consumption by humans and animals.

Detailed characterization of the DMO and PAT proteins expressed in cotton event MON 88701 led to the conclusion that neither of these proteins displays any characteristic of a potential toxin or allergen (see Section V, part 2: Potential Impact of Cotton Event MON 88701 on Animal Health and Human Safety as it Relates to the Potential Transfer of Residues into Foods of Animal Origin and Worker/Bystander Exposure to the Feed). Therefore, no negative impact is expected resulting from exposure of organisms to the DMO and PAT proteins expressed in cotton event MON 88701.

Composition analyses showed that the levels of key nutrients and anti-nutrients in seed from cotton event MON 88701 are comparable to those in conventional cotton varieties (see Section V, part 1: Potential Impact of Cotton Event MON 88701 on Livestock Nutrition). Therefore, it is very unlikely that the introduction of the novel traits may have caused unintended changes to the composition of cotton event MON 88701 that would negatively impact organisms interacting with cotton event MON 88701.

Cotton event MON 88701 will not be grown in Canada. In the event that seed from cotton event MON 88701 is accidentally released into the environment, any resulting plants would not be expected to set seed. Therefore, exposure of non-target organisms to the DMO and PAT proteins from cotton event MON 88701 is expected to be minimal to non-existent.

Based on the above, the CFIA has determined that the use of cotton event MON 88701 will not result in altered impacts on interacting organisms, including humans, when compared to currently grown cotton varieties.

5. Potential Impact of Cotton Event MON 88701 on Biodiversity

No varieties of cotton, nor any wild relatives that can readily interbreed with cotton, can grow in the Canadian environment since cotton is not adapted to the environmental conditions encountered in Canadian agricultural environments. In addition, cotton event MON 88701 has no observed or expected modifications that would allow it to survive in the Canadian environment; as a result, it is not expected to enter or survive in managed or unmanaged ecosystems in Canada. Furthermore, there is no evidence to suggest that cotton event MON 88701 would cause negative impacts on interacting organisms.

The CFIA has therefore concluded that cotton event MON 88701 does not present any adverse impacts on biodiversity in Canada.

V. Criteria for the Livestock Feed Assessment

The AFD considered the nutrient and anti-nutrient profiles of cotton MON 88701. It also took into consideration the safety of feed ingredients derived from it, including the presence of gene products, residues and metabolites in terms of animal health and human safety as it relates to the potential transfer of residues into foods of animal origin and worker/bystander exposure to the feed. Finally, the AFD sought to determine whether feeds derived from cotton MON 88701 meet the definitions and requirements of feeds as listed in Schedule IV of the Feeds Regulations.

1. Potential Impact of Cotton Event MON 88701 on Livestock Nutrition

Nutritional and Anti-Nutrient Composition:

The nutritional equivalence of cotton event MON 88701 plants was compared to those of the unsprayed, unmodified control cotton variety, and nine unsprayed, conventional control cotton varieties from eight replicated trials conducted in the U.S. during the 2010 growing season. Cottonseed samples were harvested, ginned and acid-delinted from all plots for compositional analyses. Subsamples were taken and analysed for moisture, ash, protein, crude fat, crude fibre, acid detergent fibre (ADF), neutral detergent fibre (NDF), dietary fibre (DF), amino acids, fatty acids, minerals and vitamin E. Anti-nutrients, total gossypol, free gossypol and cyclopropenoid fatty acids (malvalic, sterulic and dihydrosterulic acids) were also analysed as recommend by the Organization for Economic Co-operation and Development (OECD) consensus document for new varieties of cotton (OECD, 2009).

Composition data was analysed statistically using analysis of variance, and statistically significant differences among cottonseed types were identified and assessed (P<0.05). The biological relevance of any statistically significant differences observed among cottonseed varieties was compared within the range of the conventional control cotton varieties and published scientific literature (International Life Sciences Institute [ILSI], 2011). There were statistically significant differences between cotton event MON 88701 and the unmodified control cotton variety for moisture, ash, crude fat, carbohydrates, ADF, NDF, TDF; however, the mean values for both cottonseed types were within the natural variation found for the conventional control cotton varieties and published scientific literature (ILSI, 2011). The differences were therefore not considered biologically relevant. Except for arginine, methionine and proline, no statistically significant differences were identified between cotton event MON 88701 and the unmodified control cotton variety for the other amino acids analysed. All amino acids were within the range of the tolerance interval of the conventional varieties and/or the published scientific literature (ILSI, 2011).

Statistically significant differences were observed between cotton event MON 88701 and the unmodified control cotton variety for myristic and linoleic acids, but the differences were not considered to be biologically relevant, as the mean values were within the range of the conventional control cotton varieties and the published scientific literature (ILSI, 2011). Calcium, magnesium, manganese, zinc, potassium and vitamin E were significantly different in cotton event MON 88701 compared to the unmodified control cotton variety, but the levels were within the range of the conventional control cotton varieties and the published scientific literature (ILSI, 2011). Total gossypol, dihydrosterulic acid and free gossypol were significantly higher in cotton event MON 88701 than the unmodified control cotton variety; however, the differences were small and not repeatable within the eight individual sites. The mean values of these anti-nutrients in cotton event MON 88701 were also within the range of the conventional control cotton varieties and the published scientific literature (ILSI, 2011). Overall, observed differences in the anti-nutrient values between cotton event MON 88701 and unmodified control cotton variety were not considered to be meaningful from a biological perspective.

Conclusion:

Based on the evidence provided by Monsanto Canada Inc., the CFIA concluded that the nutritional composition of cotton event MON 88701 is similar to that of the conventional control cotton varieties grown in the trials and to that reported for other cotton varieties in the published scientific literature. Feed ingredients derived from cotton event MON 88701 are considered to meet the present definitions for cottonseed in the Feeds Regulations.

2. Potential Impact of Cotton Event MON 88701 on Animal Health and Human Safety as it Relates to the Potential Transfer of Residues into Foods of Animal Origin and Worker/Bystander Exposure to the Feed

Cotton event MON 88701 is tolerant to dicamba and glufosinate herbicides due to production of the DMO and PAT proteins. The assessment of cotton event MON 88701 evaluated the impact of the following potential hazards relative to the safety of feed ingredients derived from this event:

  • The presence of novel proteins DMO and PAT;
  • The chemical pesticide residue profile.

Novel DMO and PAT Proteins:

To obtain sufficient quantities of DMO and PAT proteins for evaluation of environmental and feed safety, it was necessary to express the demethylase and the bialaphos resistance (bar) genes in a microbial production system. The equivalency of the cotton event MON 88701-produced DMO and PAT proteins to the microbially-produced DMO and PAT proteins was evaluated by comparing their molecular weights, immunoreactivities, glycosylation, tryptic peptide mass mapping results and N-terminal sequences. Based on the results, the proteins were found to be equivalent. Demonstration of equivalence between the microbially-produced DMO and PAT proteins and the DMO and PAT proteins produced in cotton event MON 88701 allows utilization of the microbially-produced DMO and PAT proteins in studies to confirm the safety of the DMO and PAT proteins produced in cotton event MON 88701.

The potential allergenicity and toxicity of the DMO and PAT proteins to livestock were evaluated. With respect to their potential allergenicity, the sources of the demethylase and the bar genes, S. maltophilia and S. hygroscopicus respectively, are not known to produce allergens, and a bioinformatics evaluation of the DMO and PAT protein amino acid sequences confirmed the lack of relevant similarities between these proteins and known allergens. E. coli-produced DMO and PAT protein studies indicated that, unlike many allergens, these proteins are rapidly degraded in simulated gastric fluid and are not heat stable. The weight of evidence thus indicates that the DMO and PAT proteins are unlikely to be allergenic.

In terms of potential toxicity to livestock, the DMO and PAT proteins lack a mode of action to suggest that they are intrinsically toxic to livestock, and bioinformatics evaluations of the DMO and PAT protein amino acid sequences confirmed the lack of relevant similarities between the DMO and PAT proteins and known toxins. In addition, safety studies conducted using E. coli-produced DMO and PAT proteins indicated that no adverse effects were observed when the DMO and PAT proteins were ingested by mice at doses of approximately 283 and 1086 mg/kg-bw, respectively. This data indicates that the DMO and PAT proteins are unlikely to be toxic to livestock.

The livestock exposure to the DMO and PAT proteins is expected to be negligible as they are expressed at very low levels in cotton event MON 88701, they are rapidly degraded under conditions that simulate the mammalian digestive tract and they are unstable under heating conditions expected to be encountered during processing of some cotton products.

Chemical Pesticide Residue Profile:

The safety of pesticide (dicamba and glufosinate-ammonium) residues and metabolites in cotton event MON 88701 following the application of herbicides was also evaluated as part of the feed safety assessment.

Herbicide-tolerant cotton for use with dicamba has not, at this time, been the subject of any prior AFD Decisions. The safety of dicamba residues and metabolites in feed ingredients after the application of dicamba to MON 88701 cotton has not been fully assessed, as there were no regulatory points of reference available at the time of the evaluation. The AFD has therefore placed a provisional restriction on feed commodities derived from MON 88701 cotton following the application of dicamba until an authorization for dicamba application on cotton event MON 88701 has been granted by Health Canada's Pest Management Regulatory Agency (PMRA).

Conclusion:

Based on the evidence provided by Monsanto Canada Inc., it was concluded that the novel DMO and PAT protein-based herbicide tolerance traits will not confer any characteristic that would raise concerns regarding the safety of cotton event MON 88701. Any feed ingredient(s) derived from the combination of cotton event MON 88701 and dicamba may not be manufactured or sold in Canada, or imported into Canada, until an authorization for dicamba application on cotton event MON 88701 has been granted by Health Canada's PMRA.

VI. New Information Requirements

If, at any time, Monsanto Canada Inc. becomes aware of any new information regarding risk to the environment, livestock or human health that could result from the release or livestock feed use of cotton event MON 88701 or lines derived from it, Monsanto Canada Inc. is required to immediately provide such information to the CFIA . On the basis of such new information, the CFIA will re-evaluate the potential impact of cotton event MON 88701 on the environment, livestock and human health and may re-evaluate its decision with respect to the livestock feed use and environmental release authorizations of cotton event MON 88701.

VII. Regulatory Decision

Cotton event MON 88701 will not be grown in Canada nor can the seed overwinter; therefore, the release of the feed into the environment would result in neither intended nor unintended environmental effects.

Based on the review of the data and information submitted by Monsanto Canada Inc. and input from other relevant scientific sources, the AFD has concluded that the novel DMO and PAT (bar) protein-based herbicide tolerance traits will not confer to cotton event MON 88701 any characteristic that would raise concerns regarding the safety or nutritional composition of cotton event MON 88701. Cottonseed and cottonseed meal are currently listed in Schedule IV of the Feeds Regulations and are, therefore, approved for use in livestock feeds in Canada. Cotton event MON 88701 has been found to be as safe and nutritious as currently and historically grown cotton varieties. Cotton event MON 88701 and its products are considered to meet present ingredient definitions and are approved for use as livestock feed ingredients in Canada.

Taking into account this evaluation, use as livestock feed of cotton event MON 88701 is, therefore, authorized by the Animal Feed Division of the Animal Health Directorate as of June 26, 2014. Any cotton lines derived from cotton event MON 88701 may also be used as livestock feed, provided that (i) no inter-specific crosses are performed; (ii) the intended uses are similar; (iii) it is known based on characterization that these plants do not display any additional novel traits and are substantially equivalent to cotton varieties that are currently grown and permitted to be used as livestock feed in Canada, in terms of their potential environmental impact and livestock feed safety; and (iv) the novel genes are expressed at a level similar to that of the authorized line

Cotton event MON 88701 is subject to the same phytosanitary import requirements as the unmodified cotton varieties, and is required to meet the requirements of other Canadian legislation including, but not limited to, the Food and Drugs Act and the Pest Control Products Act.

Please refer to Health Canada's Decisions on Novel Foods for a description of the food safety assessment of cotton event MON 88701.

Date modified: