GM Crop Database

Database Product Description
 
MON-8817-3 (MON88017)
Host Organism
Zea mays L. L. (Maize)
 
Trait
Glyphosate herbicide tolerance and resistance to corn root worm (Coleoptera, Diabrotica sp.).
 
Trait Introduction
Agrobacterium tumefaciens-mediated plant transformation.
 
Proposed Use
Production of Z. mays for human consumption (wet mill or dry mill or seed oil), and meal and silage for livestock feed. These materials will not be grown outside the normal production area for corn.
 
Company Information
Monsanto Company
Chesterfield Village Research Center (MO)
700 Chesterfield Parkway North
St. Louis
MO  USA
 
 
Summary of Regulatory Approvals
 
Country Environment Food and/or Feed Food Feed Marketing
Argentina 2010 2010  
Australia 2006  
Canada 2006 2006 2006  
China 2007  
Colombia 2011  
European Union 2009  
Japan 2006 2006 2006  
Korea 2006 2006  
Mexico 2006  
Philippines 2006  
Taiwan 2006  
United States 2005 2005  
Click on the country name for country-specific contact and regulatory information.
Notes
Canada Authorization for unconfined release into the environment and livestock feed use expires 1 April 2007. Renewal conditional upon submission of additional research results on corn rootworm resistance management.
China Approval valid until 20 December 2010.

Introduction
 
Maize line MON88017 was genetically modified to contain two novel genes, cry3Bb1 for insect resistance, and cp4 epsps, which confers tolerance to glyphosate. Both genes were introduced into the parental maize line LH198 by Agrobacterium-mediated plant transformation.

The cry3Bb1 gene, isolated from the soil bacterium Bacillus thuringiensis (Bt) subspecies kumamotoensis, produces the insect control protein Cry3Bb1, a delta-endotoxin. Cry proteins, of which Cry3Bb1 is only one, act by selectively binding to specific sites localized on the lining of the midgut of susceptible insect species. Following binding, pores are formed that disrupt midgut ion flow, causing gut paralysis and eventual death due to bacterial sepsis. Cry3Bb1 is lethal only when eaten by the larvae of coleopteran insects (i.e., beetles), and its specificity of action is directly attributable to the presence of specific binding sites in the target insects. There are no binding sites for the delta-endotoxins of B. thuringiensis on the surface of mammalian intestinal cells, therefore, livestock animals and humans are not susceptible to these proteins. The Cry3Bb1 protein expressed in MON88017 provides protection against the western corn rootworm (Diabrotica vigifera) and northern corn rootworm (Diabrotica barberi).

MON88017 also was developed to allow the use of glyphosate, the active ingredient in the herbicide Roundup? as a weed control option. The novel plants express an herbicide tolerant form of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) derived from the common soil bacterium, Agrobacterium tumefaciens strain CP4. Glyphosate specifically binds to and inactivates EPSPS, which is involved in the synthesis of the aromatic amino acids, tyrosine, phenylalanine and tryptophan (shikimate biochemical pathway). EPSPS is present in all plants, bacteria, and fungi but not in animals, which must obtain these essential amino acids from their diet. Because the aromatic amino acid biosynthetic pathway is not present in mammalian, avian or aquatic life forms, glyphosate has little if any toxicity for these organisms (U.S. EPA, 1993; WHO, 1994; Williams et al. 2000). The EPSPS enzyme is normally present in food derived from plant and microbial sources.

Summary of Introduced Genetic Elements
 
Code Name Type Promoter, other Terminator Copies Form
CP4 epsps 5-enolpyruvyl shikimate-3-phosphate synthase  (Agrobacterium tumefaciens CP4) HT rice actin I promoter and intron sequences
chloroplast transit peptide from A. thaliana
A. tumefaciens nopaline synthase (nos) 3'-untranslated region 1 functional  
cry3Bb1 Cry3Bb1 delta-endotoxin  (Bacillus thuringiensis subsp. kumamotoensis strain EG4691) IR CaMV 35S promoter with duplicated enhancer region
5' UTR from wheat chlorophyll a/b-binding protein; rice actin gene first intron
3' UTR from wheat heat shock protein (tahsp17 3') 1 functional synthetic

Characteristics of Zea mays L. (Maize)
 
Center of Origin Reproduction Toxins Allergenicity
Mesoamerican region, now Mexico and Central America Cross-pollination via wind-borne pollen is limited, pollen viability is about 30 minutes. Hybridization reported with teosinte species and rarely with members of the genus Tripsacum. No endogenous toxins or significant levels of antinutritional factors. Although some reported cases of maize allergy, protein(s) responsible have not been identified.

Donor Organism Characteristics
 
Latin Name Gene Pathogenicity
Bacillus thuringiensis subsp. kumamotoensis cry3Bb1 While coleopterans are susceptible to oral doses of Cry3Bb1 protein, there is no evidence of toxic effects in laboratory mammals or birds. There are no significant mammalian toxins or allergens associated with the host organism.
Agrobacterium tumefaciens strain CP4 CP4 EPSPS A. tumefaciens is a common soil bacterium that is responsible for causing crown gall disease in susceptible plants. There have been no reports of adverse affects on humans or animals.

Modification Method
 
MON88017 maize was produced by Agrobacterium-mediated transformation of the hybrid maize line LH198. The T-DNA segment of the vector plasmid PV-ZMIR39 contained sequences corresponding to a synthetic variant of the cry3Bb1 gene from Bacillus thuringiensis subsp. kumamotoensis strain EG4691 and the cp4 epsps gene from Agrobacterium tumefaciens strain CP4. Transcription of the cry3Bb1 gene was directed by the 35S promoter with a duplicated enhancer region from Cauliflower Mosaic Virus, the 5? untranslated leader from the wheat chlorophyll a/b-binding protein, and was enhanced by the rice actin gene first intron. Terminator and polyadenylation sequences were derived from the 3? untranslated region of the wheat heat shock protein (tahsp17 3?).

The cp4 epsps gene, which codes for the novel protein CP4 EPSPS, was joined to the chloroplast transit peptide gene (ctp2), isolated from Arabidopsis thaliana) to target the expression of the novel protein to the chloroplast. The expression of the cp4 epsps gene was regulated by the rice actin gene promoter and enhanced by the rice actin gene first intron. Terminator and polyadenylation sequences were derived the 3? untranslated region of the nopaline synthase (NOS) coding sequence. The left border sequence (from octopine Ti plasmid pTi15955) and right border (from nopaline Ti plasmid pTiT37) contained non-coding sequences essential for the transfer of the T-DNA segment.

Characteristics of the Modification
 
The Introduced DNA
Southern blot analysis of the genomic DNA of MON 88017 demonstrated the integration of a single, intact copy of the T-DNA of PV-ZMIR39. Both novel genes, cry3Bb1 and cp4 epsps, along with their respective promoter, enhancer and terminator sequences, were completely integrated. None of the vector backbone sequences, including the spectinomycin resistance and streptomycin resistance genes, were integrated into the genome of MON88017.

Genetic Stability of the Trait
The stability of both cry3Bb1 and cp4 epsps genes were assessed using Southern blot analysis and segregation analysis across 10 generations. The integration was shown to be stable across generations and the genes segregated according to a Mendelian inheritance pattern.

Environmental Safety Considerations
 
Field Testing
Maize event MON88017 was field tested in Canada in 2003, and in the United States in 2001, 2002 and 2003. Agronomic characteristics of hybrids derived from MON88017 such as seed dormancy, vegetative vigour, early stand establishment, time to maturity, flowering period, susceptibilities to various pests and pathogens, and seed production were compared to those of unmodified counterparts. Nutritional components of MON88017, such as proximates, amino acids and fatty acids were compared with those of unmodified counterparts.

Outcrossing
Pollen production and viability were unchanged by the genetic modification resulting in MON88017, therefore pollen dispersal by wind and outcrossing frequency should be no different than for other maize varieties. Gene exchange between MON88017 and other cultivated maize varieties will be similar to that which occurs naturally between cultivated maize varieties at the present time. In the United States and Canada, where there are no plant species closely-related to maize in the wild, the risk of gene flow to other species appears remote. Feral species in the United States related to corn cannot be pollinated due to differences in chromosome number, phenology (periodicity or timing of events within an organism?s life cycle as related to climate, e.g., flowering time) and habitat.

Maize (Zea mays ssp. mays) freely hybridizes with annual teosinte (Zea mays ssp. mexicana) when in close proximity. These wild maize relatives are native to Central America and are not present in the United States, except for special plantings. Tripsacum, another genus related to Zea, contains sixteen species, of which twelve are native to Mexico and Guatemala. Three species of Tripsacum have been reported in the continental United States: T. dactyloides, T. floridanum and T. lanceolatum. Of these, T. dactyloides, Eastern Gama Grass, is the only species of widespread occurrence and of any agricultural importance. It is commonly grown as a forage grass and has been the subject of some agronomic improvement (i.e., selection and classical breeding). T. floridanum is known from southern Florida and T. lanceolatum is present in the Mule Mountains of Arizona and possibly southern New Mexico. Even though some Tripsacum species occur in areas where maize is cultivated, gene introgression from maize under natural conditions is highly unlikely, if not impossible. Hybrids of Tripsacum species with Zea mays are difficult to obtain outside of the controlled conditions of laboratory and greenhouse. Seed obtained from such crosses are often sterile or progeny have greatly reduced fertility.

Weediness Potential
The history and biology of maize indicates that non-transgenic plants of this species are not invasive in unmanaged habitats. Maize does not possess the potential to become weedy due to traits such as lack of seed dormancy, the non-shattering nature of corn cobs, and the poor competitive ability of seedlings. The data generated from field trials shows that MON88017 and derived hybrids are similar to their counterparts in this respect. Data submitted by the developer on the reproductive and survival biology of hybrids derived from MON88017 determined that early stand establishment, flowering period, vegetative vigor, time to maturity and seed production were within the normal range of expression of these traits currently displayed by commercial hybrids. No competitive advantage was conferred to MON88017, other than that conferred by resistance to rootworm and tolerance to glyphosate herbicide. These traits were demonstrated not to render maize weedy or invasive of natural habitats since none of the reproductive or growth characteristics were modified. The above considerations lead to the conclusion that MON88017 has no altered weed or invasive potential compared to currently commercialized corn.

Secondary and Non-Target Adverse Effects
The agronomic characteristics of MON88017 hybrids were shown to be within the range of values displayed by currently commercialized maize hybrids, and indicate that the growing habit of maize will not be inadvertently altered by cultivation of MON88017. Field observations did not indicate modifications of disease and pest susceptibilities, other than to rootworm, which is not known to be a principal factor restricting the establishment or distribution of maize.

Some of the genetic elements introduced into MON88017 were derived from known plant pathogens, but in all cases the genes responsible for the pathogenic qualities of the pathogen were not introduced. Therefore, the introduction of genetic material for Diabotica spp. resistance and glyphosate tolerance would not be expected to result in MON88017 expressing novel pathogenic characteristics.

The history of use and literature suggest that the bacterial Cry3Bb1 toxins are not toxic to humans, other vertebrates, and non-coleopteran invertebrates. This protein is active only against specific coleopteran insects. Data from dietary toxicity and field studies on the effect of the Cry3Bb1 protein on non-target organisms supported the environmental safety assessment of corn event MON863. In all cases, MON863 corn was demonstrated to be safe to non-target organisms. Given that MON88017 Cry3Bb1 protein differs from the MON863 CryBb1 protein by a single amino-acid, that both proteins were demonstrated to be equivalent in terms of insecticidal activity against susceptible pest insects and that the levels of Cry3Bb1 expression in both lines are similar, MON88017 is expected to be safe to previously assayed non-target organisms. The Cry3Bb1 protein expressed in MON88017 was also demonstrated to be safe to mammals.

The impact of CP4 EPSPS protein on non-target organisms, including humans, has been thoroughly assessed in previous applications for environmental safety assessments of CP4 EPSPS-expressing crops. The CP4 EPSPS protein expressed in MON88017 tissues is the same or is > 99% identical to CP4 EPSPS proteins produced in glyphosate-tolerant crops with a history of safe use. The environmental and feed safety of the CP4 EPSPS protein in corn has been previously established with, for example, the regulatory approval of NK603.

Non-transgenic maize is known to produce low levels of anti-nutrients such as raffinose and phytic acid, and the levels of these compounds in MON88017 were demonstrated to be equivalent to levels found in control lines. Therefore the genetic modification did not alter the expression of endogenous anti-nutritional factors.

Based on this data, it was determined that the unconfined release of MON88017 will not result in altered impacts when compared with currently commercialized corn on interacting organisms, including humans, with the exception of specific coleopteran pest species.


Impact on Biodiversity
MON88017 has no novel phenotypic characteristics which would extend its use beyond the current geographic range of maize production. Since maize does not out-cross to wild relatives in the united States or Canada, there will be no transfer of novel traits to unmanaged environments. In addition the novel traits were determined to pose minimal risks to non-target organisms.

MON88017 provides an alternative method to existing methods of control of rootworms, an important agricultural pest of maize. The control of agricultural pest species is a common practice that is not restricted to the environmental release of transgenic plants. Therefore, the reduction in local pest species as a result of the cultivation of MON88017 does not present a significant change from existing agricultural practices.
At present, the use of chemical insecticides to control rootworm is permitted, although crop rotation represents a major method of rootworm control ins some countries.

MON88017 also provides an alternative method of weed control in corn production. The use of broad spectrum herbicides has the intended effect of reducing local weed populations within agricultural fields and this may reduce local weed species biodiversity, and possibly other trophic levels which utilize these weed species. It must be noted, however, that reduction in weed biodiversity in agricultural fields is not unique to the use of transgenic plants, and is a common practice in virtually all modern agricultural systems. It was therefore concluded that MON88017 does not present a significantly altered impact on biodiversity in comparison to maize varieties currently being grown.

Food and/or Feed Safety Considerations
 
Dietary Exposure
Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from MON88017 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids will not be different from that for other commercially available field maize varieties.

Potential toxicity and allergenicity
The two novel proteins present in MON88017 corn have been assessed previously for safety; the CP4 EPSPS protein is present in approved lines of canola, cotton, soybean, potato and other corn events. Previous assessments have shown that CP4 EPSPS administered directly to animals at a high dose is not toxic, and the evidence indicates no potential for this protein to be allergenic in humans. Given its widespread use in approved glyphosate-tolerant crops, it now has a history of safe use in food over 10 years.

In considering the potential toxicity and allergenicity of the Cry3Bb1 variant protein, it is worth noting that Bt formulations containing Cry3Bb1 have been used safely in agriculture since 1995. Two separate acute toxicity studies in mice using the individual Cry3Bb1 variant proteins present in MON88017 and MON863 respectively confirmed the absence of mammalian toxicity in each case. Bioinformatic studies confirmed the absence of any significant amino acid similarity with known protein toxins and allergens, and in vitro digestibility studies demonstrated that Cry3Bb1 variants are rapidly degraded in the stomach following ingestion. Furthermore, processing involving heat treatment renders the Cry3Bb1 variant protein non-functional (i.e. unable to exert a toxic effect in insects). This weight of evidence indicates that the Cry3Bb1 variant protein is not toxic and is unlikely to pose an allergenic risk to humans.

Nutritional and Compositional Data
Forage and grain from MON 88017 maize, grown at three locations, were analyzed for nutritional composition and compared to that of a non-transgenic maize of similar genetic background (i.e., the conventional maize control), and to the composition of twelve conventional maize hybrids.

Forage was harvested at the late dough to early dent stages and was analyzed for proximates (crude protein, crude fat, moisture, ash and carbohydrate), acid detergent fibre, neutral detergent fibre, calcium and phosphorus. No significant differences in the levels of these components were observed between MON88017, the conventional control and the conventional hybrids.

Grain samples were obtained from mature (growth stage R6) plants harvested at three locations. The levels of several nutritional components were determined, including: proximates (crude protein, crude fat, moisture, ash, and carbohydrate); acid detergent fibre, neutral detergent fibre, total dietary fibre; minerals (calcium, phosphorus, magnesium, copper, iron, manganese, potassium, and zinc); amino acids; fatty acids; vitamins (folic acid, niacin, B1, B2, B6, and E); anti-nutrients (phytic acid, raffinose); and secondary metabolites (ferulic acid, p-coumaric acid).

Statistical analysis of the nutritional component data across all locations revealed no significant differences among MON 88017, the non-transgenic control, and the commercial hybrids, with the exception of levels of vitamin B1, and linolenic and arachidic acid, expressed as percentages of total fatty acids. The differences in linolenic and arachidic acids were not significant when the data was expressed on a dry matter basis. The levels of vitamin B1 were lower in MON 88017 compared to the non-transgenic control, but were within the 99% tolerance interval established using the twelve conventional commercial hybrids.

The levels of the antinutritional compounds phytic acid and raffinose, as well as the secondary metabolites ferulic acid and p-coumaric acid, were determined in the grain. Phytic acid occurs naturally in maize and other cereals. It is indigestible by humans and non-ruminant livestock, and also inhibits the absorption of iron and other minerals. Raffinose is an oligosaccharide found in cereals and legumes. It is cannot be digested by humans and monogastric livestock, thereby reducing the amount of metabolizable energy in foods and livestock feeds. Ferulic acid and p-coumaric acid are phenolic compounds found in cell walls; these become covalently linked to hemicelluloses during cell wall development. In ruminants, these compounds inhibit cell wall degradation by rumen microorganisms. No significant differences were observed in the levels of these antinutrients and secondary metabolites between MON 88017 and the non-transgenic control maize line. The levels of these compounds were also within the 99% tolerance interval established for the twelve conventional maize hybrids.

The results of these compositional analyses led to the conclusion that MON 88017 forage and grain is not different in nutritional and antinutritional composition compared to maize hybrids currently marketed, grown and consumed.

Links to Further Information
 
Canadian Food Inspection Agency[PDF Size: 130764 bytes]
Decision Document DD2006-57: Determination of the Safety of Monsanto Canada's Glyphosate-Tolerant, Corn-Rootworm-Protected Corn (Zea mays L.) Event MON 88017
European Food Safety Authority[PDF Size: 176472 bytes]
Scientific Opinion: Application (Reference EFSA-GMO-CZ-2005-27) for the placing on the market of the insect-resistant and herbicide-tolerant genetically modified maize MON88017, for food and feed uses, import and processing under Regulation (EC) No 1829/2003 from Monsanto.
Food Standards Australia New Zealand[PDF Size: 460541 bytes]
Final Assessment Report: Application A548, food from corn rootworm-protected & glyphosate-tolerant corn MON 88017
Health Canada Novel Foods[PDF Size: 72622 bytes]
Novel Food Information: Insect resistant, glyphosate tolerant maize event MON 88017
Japanese Biosafety Clearing House, Ministry of Environment[PDF Size: 87367 bytes]
Outline of the biological diversity risk assessment report: Type 1 use approval for MON88017
Philippines Department of Agriculture, Bureau of Plant Industry[PDF Size: 30221 bytes]
Determination of the Safety of Monsanto?s Corn MON 88017 (Insect Resistant and HerbicideTolerant Corn) for Direct use as Food, Feed and for Processing
U.S. Environmental Protection Agency[PDF Size: 187915 bytes]
Bacillus thuringiensis Cry3Bb1 protein and the genetic material necessary for its production (Vector ZMIR39) in Event MON 88017 corn (OECD Unique Identifier: MON-88?7-3) Fact Sheet
U.S. Food and Drug Administration[PDF Size: 144766 bytes]
Biotechnology Consultation Note to the File BNF No. 000097
U.S.Department of Agriculture, Animal and Plant Health Inspection Service[PDF Size: 7330066 bytes]
Monsanto Co. Petition for the Determination of Nonregulated Status for MON 88017 Corn
U.S.Department of Agriculture, Animal and Plant Health Inspection Service[PDF Size: 540016 bytes]
USDA-APHIS Decision on Monsanto Petition 04-125-01P Seeking a Determinaiton of Nonregulated Status for Bt cry3Bb1 Insect Resistant Corn Line MON 88017: Environmental Assessment

References
 
Compositional Analysis
McCann, M.C., Trujillo, W.A., Riodan, S.G., Sorbet, R., Bogdanova, N.N. and Sidhu, R.S. (2007). Comparison of the forage and grain composition from insect-protected and glyphosate-tolerance MON 88017 corn to conventional corn (Zea mays L.). J. Agric. Food Chem. 55: 4034-4042.
Poerschmann, J., Rauschen, S., Langer, U., Augustin, J. and G?ecki, T. (2008). Molecular level lignin patterns of genetically modified Bt-maize MON88017 and three conventional varieties using tetramethylammonium hydroxide (TMAH)-induced thermochemolysis J. Agric. Food Chem. 56 (24): 11906?11913.
Poerschmann, J., Rauschen, S., Langer, U., Augustin, J., Juergen and Gorecki, Tadeusz. (2009). Fatty acid patterns of genetically modified Cry3Bb1-expressing Bt-maize Mon88017 and its near-isogenic line. Journal of Agricultural and Food Chemistry 57(1): 127-132.
Environmental Fate
Rauschen, S., Nguyen, H., Schuphan, I., Jehle, J., Eber, S. (2008). Rapid degradation of the Cry3Bb1 protein from Diabrotica-resistant Bt-corn MON88017 during ensilation and fermentation in biogas production facilities. Journal of the Science of Food and Agriculture 88: 1709-1715.
Feeding Studies
Healy, C., Hammond, B. and Kirkpatrick, J. (2008). Results of a 13-week safety assurance study with rats fed grain from corn rootworm-protected, glyphosate-tolerant MON 88017 corn. Food Chem. Toxicol. 46(7): 2517-2524.
Glyphosate
Steinrucken, H.C. & Amrhein, N. (1980). The herbicide glyphosate is a potent inhibitor of 5-enolpyruvylshikimic acid-3-phosphate synthase. Biochemical and Biophysical Research Communications, 94, 1207-1212.
U.S. EPA. (1993). Reregistration Eligibility Decision (RED): Glyphosate. Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, D.C.
WHO. (1994). Glyphosate. World Health Organization (WHO), International Programme of Chemical Safety (IPCS), Geneva. Environmental Health Criteria No. 159.
Williams, G.M., Kroes, R. & Munro, I.C. (2000). Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regulatory Toxicology and Pharmacology 31, 117-165.
Nutritional Equivalence
Taylor, M.L., Hartnell, G., Nemeth, M., Karunanandaa, K. and George, B. (2005). Comparison of broiler performance when fed diets containing corn grain with insect-protected (corn rootworm and European corn borer) and herbicide-tolerant (glyphosate) traits, control corn, or commercial reference corn--revisited. Poutry Science 84(12): 1893-1899.
Taylor, M.L., Hartnell, G., Nemeth, M., Karunanandaa, K. and George, B. (2005). Comparison of broiler performance when fed diets containing corn grain with insect-protected (corn rootworm and European corn borer) and herbicide-tolerant (glyphosate) traits, control corn, or commercial reference corn. Poultry Science 84(4): 987-593.
Potential Non-Target Organism Effects
Li, Y., Meissle, M. and Romeis, J. (2008). Consumption of Bt maize pollen expressing Cry1Ab or Cry3Bb1 does not harm adult green Lacewings, Chrysoperla carnea (Neuroptera: Chrysopidae). PLoS ONE 3(8): e2909.
Meissle, M., Pilz, C. and Romeis, J. (2009). Susceptibility of Diabrotica virgifera virgifera (Coileoptera-Chrysomelidae) to the entomopathogenic fungus Metarhizium anisopliae when feeding on Bacillus thruingiensis Cry3Bb1-expressing maize. Applied and Environmental Microbiology 75(12): 3937-3943.
Rauschen, S., Schultheis, E., Pagel-Wieder, S., Schuphan, I. and Eber, S. (2009). Impact of Bt-corn MON88017 in comparison to three conventional lines on Trigonotylus caelestialium (Kirkaldy) (Heteroptera: Miridae) field densities. Transgenic Research 18(2): 203-14.


THIS RECORD WAS LAST MODIFIED ON SUNDAY, NOVEMBER 08, 2009
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