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OECD Unique Identifier details

MON-88Ø17-3
Commodity: Corn / Maize
Traits: Coleoptera resistance,Glyphosate tolerance
Australia
Name of product applicant: Monsanto Australia Ltd
Summary of application:
Corn plants are susceptible to damage from the feeding of a range of insect pests including corn rootworm (Diabrotica spp.). Corn line 88017 expresses a variant of the Cry3Bb1 protein isolated from the common soil bacterium Bacillus thuringiensis (Bt) subspecies kumamotoensis. This Bt protein is toxic to specific Coleopteran insects, including three significant pests of corn: Western corn rootworm (Diabrotica vigifera), Northern corn rootworm (Diabrotica berberi) and Mexican corn rootworm (Diabrotica vigifera zeae).

The applicant previously developed corn line MON 863, which has been genetically modified (GM) for protection against corn rootworm. Traditional breeding techniques were subsequently used to cross this line with another GM inbred line, expressing tolerance to the broad-spectrum herbicide glyphosate. However, using traditional breeding methods to introduce both traits is considered inefficient and time consuming and therefore MON 88017 corn was developed using a two-gene insertion event that simultaneously creates a single variety of corn containing both agronomic traits.

The glyphosate tolerance trait in MON 88017 is due to the expression of the bacterial enzyme 5-enolpyruvyl-3-shikimate phosphate synthase (EPSPS) from Agrobacterium sp. strain CP4. The EPSPS enzyme is present in all plants, bacteria and fungi and is essential for aromatic amino acid biosynthesis. The normal mode of action of glyphosate is to bind to the endogenous plant EPSPS, blocking the activity of the enzyme and resulting in a lack of aromatic amino acids in cells, which subsequently leads to the death of the plant. The bacterial EPSPS enzyme has a lower binding affinity for glyphosate, and therefore expression of CP4 EPSPS in the plant allows continued production of aromatic amino acids in the presence of the herbicide.

Corn, together with rice and wheat, is one of the most important cereal crops in the world with total production of 591 million tonnes in 2000 (FAOSTAT Database 2001). The majority of grain and forage derived from maize is used in animal feed. Maize grain is also used for industrial products such as ethyl alcohol and highly refined starch. Domestic production of corn in Australia and New Zealand is supplemented by the import of a small amount of cornbased food ingredients, largely high-fructose corn syrup, which is not currently manufactured in either country. Corn products are processed into breakfast cereals, baking products, extruded confectionery and corn chips. Other food ingredients such as oils and cornstarch are also imported and used by the food industry for the manufacture of dessert mixes and canned foods.
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Date of authorization: 03/08/2006
Scope of authorization: Food
Links to the information on the same product in other databases maintained by relevant international organizations, as appropriate. (We recommend providing links to only those databases to which your country has officially contributed.): OECD BioTrack Product Database
Summary of the safety assessment:
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Where detection method protocols and appropriate reference material (non-viable, or in certain circumstances, viable) suitable for low-level situation may be obtained:
Relevant links to documents and information prepared by the competent authority responsible for the safety assessment: Application A548 - Food Derived from Corn Rootworm & Glyphosate - Tolerant Corn MON 88017
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E-mail:
janet.gorst@foodstandards.gov.au
Organization/agency name (Full name):
Food Standards Australia New Zealand
Contact person name:
Janet Gorst
Website:
Physical full address:
Boeing Building, 55 Blackall Street, Barton ACT 2600, Australia
Phone number:
+61 2 6271 2266
Fax number:
+61 2 6271 2278
Country introduction:
Food Standards Australia New Zealand (FSANZ) is the regulatory agency responsible for the development of food standards in Australia and New Zealand. The main office (approximately 120 staff) is located in Canberra (in the Australian Capital Territory) and the smaller New Zealand office (approximately 15 staff) is located in Wellington on the North Island. The Food Standards Australia New Zealand Act 1991 establishes the mechanisms for the development and variation of joint food regulatory measures and creates FSANZ as the agency responsible for the development and maintenance of a joint Australia New Zealand Food Standards Code (the Code). The Code is read in conjunction with corresponding NZ and State & Territory food legislation as well as other appropriate legislative requirements (e.g. Trade Practices; Fair Trading). Within the Code, Standard 1.5.2 deals with Foods produced using Gene Technology. Applicants seeking to have a GM food approved, request a variation to Std 1.5.2 to have the GM food (from a particular line) included in the Schedule to Std 1.5.2. Only those GM foods listed in the Schedule can legally enter the food supply. An Application Handbook provides information that is required to make an application to vary the Code. This Handbook is a legal document and therefore the specified mandatory information must be supplied. For GM foods, there is also a Guidance Document that, as the name suggests, provides applicants with further details and background information on the data needed for the safety assessment of GM foods. The assessment process must be completed within a statutory timeframe (9 - 12 months depending on the complexity of the application) and involves at least one public consultation period. All GM applications involve an Exclusive Capturable Commercial Benefit i.e. applicants are required to pay a fee (outlined in the Application Handbook). Following the last public consultation, an Approval Report is prepared and is considered by the FSANZ Board who make a decision about whether the requested variation to the Code should be approved or not. The Board's decision is then passed on to the Legislative and Governance Forum on Food Regulation (the Forum), a committee comprising senior goevernment Ministers from Australia and NZ. This Committee has approximately 2 months to review the Board's decision. If the Board's approval is accepted by the Forum, the approval is then gazetted and becomes law.
Useful links
Relevant documents
Stacked events:
FSANZ does not: Separately assess food from stacked event lines where food from the GM parents has already been approved; Mandate notification of stacked events by developers; Notify the public of stacked event ‘approvals’; List food derived from stacked event lines in the Code, unless the stacked event line has been separately assessed as a single line e.g. Application A518: MXB-13 cotton (DAS-21023-5 x DAS-24236-5)
Contact details of the competent authority(s) responsible for the safety assessment and the product applicant:
Food Standards Australia New Zealand (FSANZ) (http://www.foodstandards.gov.au)
Brazil
Name of product applicant: Monsanto do Brasil Ltda.
Summary of application:
commercial release of insect resistant and glyphosate tolerant genetically modified corn styled MON88017
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Date of authorization: 16/12/2010
Scope of authorization: Food and feed
Links to the information on the same product in other databases maintained by relevant international organizations, as appropriate. (We recommend providing links to only those databases to which your country has officially contributed.): Center for Environmental Risk Assessment
Summary of the safety assessment:
Corn MON 88017 (Event 88017) was produced by transformation of immature A x Hi-II corn embryos mediated by Agrobacterium sp. Molecular analysis shows that corn MON 88017 contains a single and intact segment containing two cassettes of the expression, that is to say, the coding sequence of gene cp4 epsps and the coding sequence of gene cry3Bb1, respectively. The number of inserts was determined showing that corn MON 88017 contains one copy of the expression cassette DNA (genes cry3Bb1 and cp4 epsps) introduced in a single integration locus of the corn genome with all genetic elements intact. Segregation analyses conducted in ten generations confirmed hereditability and stability of genes cp4 epsps and cry3Bb1 in MON 88017 corn. The expression products of genes cry3Bb1 and cp4 epsps introduced in MON 88017 corn are proteins Cry3Bb1 and CP4 EPSPS, respectively. Protein CP4 EPSPS accounts for the characteristics of tolerance to the glyphosate herbicide, while protein Cry3Bb1 is responsible for the characteristics of resistance to pest coleopteran larvae of the Diabrotica genus. The donor organism of gene cry3Bb1 is Bacillus thuringiensis, a sporule forming gram-positive bacterium, while the donor of the gene cp4 epsps is Agrobacterium sp., Strain CP4, which produces a EPSPS protein naturally tolerant to glyphosate. Expression levels of proteins Cry3Bb1 and CP4 EPSPS in different tissues of MON 88017 corn were assessed from cultivation of MON 88017 corn and conventional corn in the United States and in Brazil. Expression data of proteins Cry3Bb1 and CP4 EPSPS on corn MON 88017 in Brazil and the United States showed values that promote efficiency in controlling larvae of pest insects of the Diabrotica genus and tolerance to glyphosate in this genetically modified corn. No pleiotropic effect was recorded on MON 88017 corn during the field experiments conducted in different countries and also from its commercial use. Up to this moment, there are no examples of interactive effects between proteins Cry, such as Cry3Bb1, and protein CP4 EPSPS . From the viewpoint of alimentary safety of corn MON 88017 and the expressed proteins Cry3Bb1 and CP4 EPSPS, studies of chemical and nutritional composition, safety of proteins Cry3Bb1 and CP4 EPSPS present in the diet, in food and rations derived from MON 88017 corn, and allergenicity of proteins Cry3Bb1 and CP4 EPSPS were assessed regarding risks for humans and animals. In terms of alimentary safety, corn MON 88017 displayed a behavior substantially similar to that of conventional corn, as well as other conventional hybrids. Proteins Cry3Bb1 and CP4 EPSPS were assessed for their toxicity potential to humans and animals. Acute oral toxicity studies with mice showed that proteins Cry3Bb1 and CP4 EPSPS do not display acute toxicity and failed to cause any adverse effect. Bioinformatics analyses demonstrated that proteins Cry3Bb1 and CP4 EPSPS do not share structural and sequential similarities with known toxins and biologically active proteins that cause adverse effects to human and animal health. Proteins Cry3Bb1 and CP4 EPSPS come from non-allergenic sources, are not similar to known allergens and are rapidly digested in simulated gastric juice, besides being a very small portion of the protein present in kernels of corn MON 88017. This pool of data enable a conclusion that proteins Cry3Bb1 and CP4 EPSPS show negligible likelihood to cause allergies and that corn MON 88017 is as safe as conventional corn regarding allergenicity risk. From the environmental safety viewpoint, studies were conducted with MON 88017 corn in the United States and Brazil. These studies included assessments of phenotypic agronomic characteristics in the field, phenotypic and ecologic assessments, ecological interactions, gene flow and coexistence potential and assessment as a potential pest plant. Studies of phenotypic agronomic characteristics in the fields for experiments conducted in the United States and Brazil showed that corn MON 88017 and the control corn are equivalent and have similar behavior in the environment. Assessment of ecologic interactions in experiments conducted in the United States and Brazil based on monitoring of specific insects, diseases and abiotic stresses failed to show differences in susceptibility to pests and environmental stresses. Phenotypic and ecologic data indicated that MON 88017 corn does not grant any selective advantage to corn and is as safe as its conventional control corn. An assessment of potential gene flow showed that MON 88017 corn is similar to conventional corn. Agronomic and phenotypic characteristics of MON 88017 corn were assessed regarding potential as a pest plant, and the data collected enabled a conclusion that MON 88017 corn does not pose risk of changing into a plant pest nor of generating significant ecologic impact when compared with conventional corn. Besides the data supplied by applicant, CTNBio consulted the independent scientific literature to examine alimentary and environmental safety and occurrence of any independent effect from this transformation event. CTNBio determines that the post-commercial release of MON 88017 corn shall follow the parameters approved at the 135th common meeting held on August 19, 2010. TECHNICAL OPINION I. Identification of GMO Name: MON 88017 corn Applicant: Monsanto do Brasil Ltda. Species: Zea mays L. Inserted characteristics: Resistance to pest insects and tolerance to glyphosate insecticide Method of introduction: Plant transformation mediated by Agrobacterium sp. Proposed use: Releasing into the environment, marketing, consumption and any other activities related to this GMO and its derivatives. II. General Information Corn (Zea mays L.) in Brazil is the second most farmed grain, second only to soybean Pests in corn tillage, if not appropriately controlled, significantly reduce grain yield and quality. Corn yield is also negatively affected by attack of different pest insects. One of the pest insects in corn culture is Diabrotica speciosa (Coleoptera: Chrysomelidae). The larvae of D. speciosa display underground habits and feed on corn roots causing the death of recently germinated plants. Damages caused by larvae of D. speciosa in corn take place in a period from one to two months of the plant development, affecting mainly the adventitious roots(1). By feeding on adventitious roots, the larvae disfigure the plant, leaving them more susceptible to lodging, and eventually cause the plants to curve, the origin of a symptom known as “goose neck”(1). Consumption of corn roots by larvae of D. speciosa reduce the ability of the plant to absorb water and nutrients, limiting its producing ability, making the plants more susceptible to infections by root diseases and falling, resulting in poor yield. D. speciosa adults feed on corn leaves, which may be misinterpreted as initial damages caused by the armyworm. Adults of D. speciosa also feed on corn style-stigma, negatively affecting fertilization and grain formation. In Brazil, adults D. speciosa occur in all states and regions, and attacks by Diabrotica larvae had damaged the root system of corn plants, in irrigated areas(1). MON 88017 corn, developed by recombinant DNA techniques, is tolerant to the action of glyphosate insecticide and protected against damages caused by larvae of pest coleopteran of the genus Diabrotica. MON 88017 corn offers the opportunity of applying glyphosate in post-emergence for controlling a large range of pest plants, with a minimum risk of injuries to the corn and shall offer to Brazilian farmers, who have problems with this pest in their areas, a safe and effective alternative to the protection of corn plants against an attack by Diabrotica larvae(1). III. Description of the GMO and Expressed Proteins MON 88017 corn was produced by transforming immature embryos of A X Hi-II corn mediated by lineage ABt Agrobacterium tumefasciens, containing plasmid PV-ZMIR39. This plasmid (PV-ZMIR39) is a transformation vector derived from Agrobacterium tumefasciens disarmed and binary, containing the two borders (left and right) of the T DNA to facilitate the transformation. The inserted DNA region contains the gene expression cassettes for cp4 epsps and cry3Bb1 and corresponds to the PV-ZMIR39 plasmid portion integrated to the corn genome during the transformation process. The plasmid region integrated to the corn genome contains the cassettes of gene cp4 epsps, coding protein CP4 EPSPS that grants tolerance to the glyphosate herbicide, and gene cry3Bb1 codifying protein Cry3Bb1, responsible for the resistance to coleopteran pests larvae of the genus Diabrotica. The insert integrated to the corn genome includes the two cassettes of expression: the sequence codifying gene cp4 epsps associated to the sequence of the chloroplast transit peptide 2 (CTP2), regulated by the sequence of the non-codifying 5’ end of the actine 1 sequence of rice (ract 1) containing the promoter and the first introns, and sequence 3’ of nopaline synthase (NO 3’) polyadenylation and the codifying region of gene cry3Bb1 regulated by the improved plant promoter 35S (e35S), a leading untranslated 5’ sequence of the bonding protein to chlorophyll a/b of wheat (wheat CAB leader), the intron rzct1, and the untranslated 3’ region of the codifying sequence of the heat shock protein 17.3 of wheat (tahsp 17 3’), which finalizes the translation and supplies the sign for polyadenylation of messenger RNA (mRNA)(1). The cp4 epsps gene introduced in MON 88017 corn originates from Agrobacterium sp. strain CP4, a common soil bacterium. This sequenced gene, codifies an EPSPS protein of 57.6 kDa, which consists of a single 455 amino acids polypeptide(2). In plants, endogenous EP4P4 enzyme is localized at the chloroplast. Therefore, in plasmid PV-ZMIR39 a CPT2 coding sequence was associated to the sequence coding gene cp4 epsps to direct transportation of CP4 EPSPS protein to the chloroplast. The directed protein CTP2-CP4 EPSPS contains 531 amino acids with a molecular weight of 55.8 kDa(1). In conventional plants, glyphosate bonds to the EPSPS enzyme that is endogenous to the plants, which checks the biosynthesis of 5-enolpyruvylshikimate-3-phosphate (EPSPS), depriving the plants to produce amino acids essential to their growth and development(3,4). In Roundup Ready® plants, protein CP4 EPSPS reconstructs the shikimic acid path, and is able to synthesize continuously the aromatic amino acids, even in presence of glyphosate(2). The cry3Bb1 gene sequence introduced in MON 88017 corn comes from Bacillus thuringiensis (subspecies kumamotoensis) strain EG4691(5), which was modified to code six specific amino acid substitutions, resulting in the cry3Bb1 coding sequence present in amino acid PV-ZMIR39(6). Protein Cry3Bb1 produced in MON 88017 corn belongs to a class of Cry3Bb1 that shares >95% of the amino acid sequence homology(7). This protein is a variant of a native type Cry3Bb1 protein with which it shares an amino acid sequence identity of 99.1%, differing in six of the 652 amino acid residues. In MON 88017 corn, protein Cry3Bb1 was richly characterized, displays 653 amino acid residues and contains an additional amino acid (alanine) in position 2, since it is necessary to establish an Nco I restriction site for the development of the plant expression plasmid PV-ZMIR39(1). Molecular analyses confirmed that the MON 88017 corn contains one single and intact insert, integrated in a single locus of the corn genome, with all genetic elements intact, where no region of plasmid PV-ZMIR39 is present in the transformation event generated(1). The integrated insert contains the two expression cassettes: the coding sequence of gene cp4 epsps and the coding region of gene cry3Bb1(1). Results from the molecular analysis support the conclusion that only whole CP4 EPSPS and Cry3Bb1 proteins are coded by the DNA inserted in the MON 88017 corn(1). Segregation analysis were conducted in ten generations to determine hereditability of genes cp4 epsps and cry3Bb1. The results of such analysis are consistent with what was expected from an insertion of cry3Bb1 and cp4 epsps in a single locus that segregates according to Mendelian laws. Southern blot analysis in different generations confirmed the stability of the DNA integrated to MON 88017 corn(1). The products of genes cp4 epsps and cry3Bb1 inserted in MON 88017 corn are proteins CP4 EPSPS and Cry3Bb1, respectively. A detailed characterization of proteins Cry3Bb1 and CP4 EPSPS produced in MON 88017 corn and E. coli included identity, molecular weight equivalence, immunoreactivity, glycosylation and functional activity. Results achieved show that proteins CP4EPSPS and Cry3Bb1 produced in the plant and in E. coli are physically, chemically and functionally equivalent and that no sign of hybridization was recorded in proteins CP4 EPSPS and Cry3Bb1 produced in either the plant or E. coli, supporting the conclusion that the proteins have not been glycosylated(1). Expression levels of proteins CP4 EPSPS and Cry3Bb1 in different corn tissues were assessed by ELISA (Enzyme-Linked ImmunoSorbent Assay). In order to produce the tissues to be analyzed, MON 88017 and conventional corns were planted in five locations in the United States (2005 harvest)(1) and in four locations in Brazil (2008/2009 harvest)(1,40). In the United States, the average expression of CP4 EPSPS protein (weight in dry base-Wdb) among the five locations were: 270µg/g in pollen, 56µg/g in roughage, 45µg/g in fodder, 24µg/g in root fodder, 24µg/g in senescent roots and 3.3µg/g in kernels. The average Cry3Bb1 (Wdb) protein expression among the locations were 13µg/g in pollen, 160µg/g in style-stigma, 54µg/g in roughage, 82µg/g in root fodder, 69µg/g in senescent roots and 4.4µg/g in kernels and 70µg/g in fodder. In Brazil, the average levels of CP4 EPSPS (Wdb) protein among the four locations remained in the range from 88-130µg/g in leaves, 2.6-4.0µg/g in kernels, 24 30µg/g in roughage, and 3.4 14µg/g in roots. Average Cry3Bb1 (Wdb) protein levels among the four locations were in the interval of 110-190µg/g in leaves, 3.0-8.3µg/g in kernels, 17-49µg/g in roughage, 23-79µg/g in roots. Data on expression levels of Cry3Bb1 and CP4 EPSPS proteins in m88corn for tissues of roughage, leave, kernels and roots (studied in Brazil and in the United States) showed figures that promote efficacy in controlling larvae of pest coleopteran of genus Diabrotica and tolerance to glyphosate in MON 88017 corn(1). No pleiotropic effect was recorded in MON 88017 corn during the field experiments conducted in different countries nor from its commercial use(1). Significant changes in morphology, growth and development of MON 88017 corn were not found when compared to conventional corn, both in field experiments, including those conducted in Brazil and in commercial fields in different countries. Agronomic assessment essays conducted in Brazil during the 2007/2008 and 2008/2009 harvests failed to show any pleiotropic and epistatic effect, and the agronomic and phenotypic characteristics of MON 88017 corn were not changed because of the genetic change when compared with conventional corn, except for expression of characteristics such as resistance to pest coleopteran larvae of genus Diabrotica and tolerance to glyphosate(1). Absence of interaction between these two proteins of very different natures is evidenced by the available scientific knowledge(1). Expression levels of proteins Cry3Bb1 and CP4 EPSPS on MON 88017 corn are low, yet sufficient to grant the respective characteristics of resistance to pest coleopterans larvae of the Diabrotic genus and tolerance to glyphosate. Action modes and safety of proteins Cry3Bb1 and CP4 EPSPS are well known; it is recognized that Cry proteins, such as Cry3Bb1 have metabolic pathways different from that of protein CP4 EPSPS, locus of biologic activity of Cry and CP4 EPSPS proteins are different, that is to say, proteins Cry, such as Cry3Bb1 act in the cytoplasm, while protein CP4 EPSPS is directed to the chloroplast and the history of safe use of proteins Cry and CP4 EPSPS in other products expressing these proteins at the same time shows that, up to this moment in time, there were no records of adverse effects from the expression of these proteins in a same plant(1). From the foregoing, we conclude that up to now there are no examples of interactive effects between proteins Cry, such as Cry3Bb1 and protein CP4 EPSPS. The absence of interaction between proteins Cry3Bb1 and CP4 EPSPS enabled each protein to be tested independently in safety assessment studies(8). IV. Aspects Related to Human and Animal Health From the viewpoint of alimentary safety assessment of MON 88017 corn and proteins Cry3Bb1 and CP4 EPSPS expressed in it, several studies were submitted in the Alimentary Biosafety Report(1). The studies included data on chemical and nutritional composition of MON 88017 corn, safety of donor organisms of genes cry3Bb1 (Bacillus thuringiensis) and cp4 epsps (Agrobacterium sp. strain CP4), safety of proteins Cry3Bb1 and CP4 EPSPS (present in the diet, food and rations derived from MON 88017 corn, and the potential toxicity and allergenicity of proteins Cry3Bb1 and CP4 EPSPS. All such different aspects were assessed regarding risks for humans and animals. As part of the alimentary safety assessment, analyses of chemical and nutritional composition of MON 88017 corn were conducted comparatively with the conventional control corn, featuring a genetic background similar and with commercial hybrids (references). The experiments were made in three locations in the United States (2002 harvest) and three locations in Brazil (2007/2008 harvests). Data recorded for roughage and kernels in the two countries included, in general, centesimal component (proteins, fats, ashes and humidity), fibers, minerals, amino acids, fat acids, vitamins, antinutrients, metabolites and carbohydrates(1, 21, 22, 40). In the United States, in total, 77 components were determined (nine in roughage and 68 in kernels). Fifteen components with >50% of observations below the level of qualification (LOQ) were discarded from the statistical analyses. Therefore, 62 components were statistically assessed (nine in roughage and 53 in kernels) for compositional equivalence of MON 88017 corn. A total of 248 comparisons (four groups of analyses times 62 assessed components) were conducted between MON 88017 corn and conventional corn. Results of the analyses showed no statistically relevant difference between MON 88017 and conventional corn(1). The data and information above support the conclusion that kernels and roughage of corn MON 88017 are equivalent to kernels and roughage of conventional corn in what relates to composition and nutritional value(1). In Brazil, MON 88017 corn, control corn and commercial references were produced in experiments conducted during the 2007/2008 harvest in three representative locations of corn farming in the country(1, 40). Samples of MON 88017 corn kernels and roughage were analyzed for centesimal components (ashes, fat, humidity, proteins and carbohydrates). In all locations, the values of centesimal components in roughage and kernels of MON 88017 corn were comparable to values of the control corn. In each individual location, the average values of centesimal components remained within the control interval, in each individual location or within the reference values calculated for a pooling of such locations. All average values for centesimal components assessed in roughage and kernels of MON 88017 corn remained within the intervals of the ILSI Crop Composition Database(1, 40). Therefore, results of analyses conducted in Brazil show that kernels and roughage of MON 88017 corn are equivalent to kernels and roughage of conventional corn regarding composition and nutritional value(1). Safety of genes cry3Bb1 and cp4 epsps donor organisms was assessed. The donor of gene cry3Bb1 (coding protein Cry3Bb1) is Bacillus thuringiensis, different lineages of which have been commercially used for over 40 years to produce microbial formulations with insecticide activity to be used in agriculture(10). The conclusions related to absence of threat of mixing Bacillus thuringiensis and Cry proteins in food and rations were based on absence of adverse effects for mammals in numerous toxicological studies and historic agricultural use(11, 12, 13, 14). There are no records of adverse effects for humans during the lengthy period of use of over 40 years caused by these products(10, 13). Protein CP4 EPSPS present in MON 88017 corn is similar to EPSPS proteins consumed in a variety of alimentary and ration sources. Protein CP4 EPSPS is homologous to EPSPS proteins naturally present in plants, including cultures used for food (for instance, soybean and corn) and fungal and microbial alimentary sources, such as yeasts (Saccharomyces cerevisiae), all displaying a history of safe consumption by humans(1, 15). The similarity between the CP4 EPSPS and other EPSPS proteins present in a variety of foods is an aspect important for the safety of these proteins to human and animal health. Moreover, the ubiquitous presence of homolog EPSPS enzymes in cultures used as food and common microorganisms establishes that EPSPS proteins and their enzymatic activity do not a threat to human and animal consumption of products containing such proteins(1). Safety of CP4 EPSPS and Cry3Bb1 present in the diet, food and rations derived from MON 88017 corn was assessed regarding potential toxicity to humans and animals. The assessment based on the assumption that a protein is not toxic if: (a) the protein possesses a safe history of use; (b) there is no structural similarity with known toxins or other biologically active proteins that may cause adverse effects to humans and animals; (c) the protein fails to cause acute toxic effect to mammals. Besides, the low concentration of heterolog proteins in tissues of plants that are consumed and the rapid digestion of such proteins in simulated digestive fluids provide additional information on their safety(1). Potential synergistic and antagonistic effects between proteins Cry3Bb1 and CP4 EPSPS were taken into account in assessing potential toxicity. Demonstration of no interaction between the proteins enables their testing independently from assessment and safety studies(16). Proteins Cry3Bb1 and CP4 EPSPS were assessed for potential toxicity to humans and animals according to the Codex Alimentarius Commission(1) recommendations. The two proteins have a long record of safe use, no structural similarity with known toxins or biologically active proteins affecting mammals(1). Analyses to examine structural similarities of proteins Cry3Bb1 and CP4 EPSPS with other admittedly toxic or pharmacologically active proteins that are relevant to human or animal health were conducted using ALLPEPTIDES and TOXIN5 databanks. Bioinformatic analyses showed that proteins Cry3Bb1 and CP4 EPSPS fail to share structural and sequence similarities with known toxins or biologically active proteins that may cause adverse effects to human and animal health(1). Studies of oral acute toxicity in mice with proteins Cry3Bb1 and CP4 EPSPS purified from E. coli were conducted(1,15). The studies of oral acute toxicity with mice evidenced that proteins Cry3Bb1 and CP4 EPSPS display no acute toxicity and do not cause any adverse effect, even in the highest test doses, which reached 572 mg/kg and 1,930mg/kg of corporal weight, respectively(1, 15). Proteins Cry3Bb1 and CP4 EPSPS represent nor more than 0.011% and 0.0046% of total protein contained in kernels of MON 88017 corn, respectively. These data, taken in aggregate, support the conclusion that it is highly unlikely and unexpected that proteins Cry3Bb1 and CP4 EPSPS may cause any toxic effect in humans and animals(1). Pharmacological assessments are irrelevant for proteins Cry3Bb1 and CP4 EPSPS as MON 88017 corn is not a product devised for pharmacological use(1). Regarding potential allergenic assessment of proteins Cry3Bb1 and CP4 EPSPS in MON 88017 corn, the characteristics of such proteins with known allergens were considered based on the assumption that a protein is not-allergenic if: (a) it has a safe use history, (b) there is no structural similarity with known allergens based on the sequence of amino acids, (c) the protein is rapidly digested in simulated gastric fluid, and (d) it represents just a small portion of total proteins in the kernel(1). Proteins Cry3Bb1 and CP4 EPSPS were assessed according to recommendations on the guideline for assessment of potential allergenicity of new proteins contained in the Codex Alimentarius Commission(17). Proteins Cry3Bb1 and CP4 EPSPS are derived from Bacillus thuringiensis and Agrobacterium sp. strain CP4, respectively, which are organisms that display a long history of safe use. Bioinformatics analyses for assessing similarity with allergens and identify peptides immunologically relevant conducted for proteins Cry3Bb1 and CP4 EPSPS expressed in MON 88017 corn, using a allergen databank (AD4) with algorithms FASTA and IDENTITYSEARCH showed that these proteins do not share similarities in structure and immunology aspects of amino acid sequences that are relevant in terms of known allergens(1). Therefore, it is highly unlikely that proteins Cry3Bb1 and CP4 EPSPS contain epitopes displaying crossed immunological reaction(1). In vitro digestibility essays of proteins Cry3Bb1 and CP4 EPSPS in gastric (SGF) and intestinal (SIF) fluids showed that these proteins were rapidly digested when incubated in SGF and SIF. For protein Cry3Bb1, 98% of the whole protein (~75kDa) in SGF was digested in 15 seconds and 99.8% of Cry3Bb1 was digested in one minute(1). These results suggest that protein Cry3Bb1 will be rapidly digested in the digestive tract of mammals. The fact that Cry3Bb1 protein is rapidly digested in simulated gastric fluid makes unlikely that it may act as a alimentary allergen(1). Protein CP4 EPSPS demonstrated to be rapidly degraded in vitro, using simulated digestive fluids(15). In SGF, most part of protein CP4 EPSPS showed degradation after 15 seconds of digestion (lowest tested time) (15) and in SIF, over 50% of protein CP4 EPSPS was degraded after 10 minutes of incubation(1, 15, 18). The fact that protein CP4 EPSPS is promptly digested in simulated gastric fluid makes unlikely that it may act as a alimentary allergen(1). The percentage of Cry3Bb1 and CP5 EPSPS proteins, as against total protein, present in the kernel of MON 88017 corn represent no more than 0.011% and 0.0046%, respectively, and are a very small portion of the protein present in MON 88017 corn kernels(1). Taken as a whole, all such data support the conclusion that proteins Cry3Bb1 and CP4 EPSPS are very unlikely to cause allergies and that MON 88017 corn is as safe as conventional corn regarding the allergenicity risk(1). V. Environmental Aspects Regarding assessment of environmental safety of MON 88017 corn, several studies submitted in the Alimentary Biosafety Report(1) will be discussed below. Regarding ecologic impact of MON 88017 corn phenotypic and agronomic characteristics and ecologic interactions (plant-insect, plant-disease, and plant- biotic and abiotic stresses) were assessed in studies conducted in the United States(1, 21, 22) and Brazil(1, 40, 41, 42, 43). Assessment of environmental safety of MON 88017 corn was conducted to study the potential gene flow of corn MON 88017 and the potential of this corn as a plant pest, and aspects on the impact of MON 88017 corn in agronomic practices of MON 88017 corn were also presented. Modern corn is the result of a long domestication process (selection and genetic improvement) and corn features low biologic ability to survive as a spontaneous or voluntary plant. Genetics and plant improvement experts are unanimous in stating that the species Zea mays L. cannot survive in a natural or farming environment without human intervention(1). Gene flow is a natural biologic process that takes place in most cultures. Corn and the annual teosinte (Zea mays subspecies Mexicana) are genetically compatible, pollinated by wind and, in certain areas of Mexico and Guatemala, cross freely when located close to each other. However, teosinte is not present in Brazil, except occasionally as part of botanical collections. Therefore, the environmental consequence of MON 88017 corn pollen transfer to feral species of corn plants in Brazil can be taken as negligible(1), being unlikely the sexual crossing of MON 88017 corn with compatible species of corn in Brazil(1). Knowledge on gene flow is fundamental to establish conclusions on the likelihood of coexistence between different types of corn(1). In Brazil, a study on assessment of genetically modified corn gene flow was made in the Experimental Units of Monsanto do Brasil Ltda., located in Ponta Grossa (PR) and Santa Helena de Goiás (GO). The results of the experiment showed that that frequency of gene flow depends on the slope of the terrain and the predominant direction of the wind at the flowering time, being the flow benefited by descending slopes and favorable wind(1). Assessment of potential gene flow from plants of MON 88017 corn to other plants of conventional corn in cultivation areas indicated that gene flow of MON 88017 corn was similar to what happens in conventional corn(1). Assessment of phenotypic, agronomic and ecologic interactions of MON 88017 corn were conducted in both the United States and Brazil, in field experiments. In the United States, during the assessments of MON 88017 corn conducted during the 2001(21) and 2002(21) crops, data were collected for phenotypic characteristics and studies of ecologic interactions, taking into consideration: (1) dormancy and germination. (2) emergence and vegetative growth, (3) reproductive phase, (4) retention of seeds in the plant, and (5) interactions of the plant with insects, diseases and abiotic stresses(1, 21, 22). Phenotypic and agronomic data collected and assessed in the United States support the conclusion that MON 88017 corn fails to pose a risk of changing into a pest plant or generate significant ecologic impact when compared to conventional corn(1). During the assessments of MON 88017 corn conducted in Brazil on the 2007/2008 and 2008/2009 crops(1, 40, 41, 42, 43), data for five parameters of dormancy/germination, two pollen characteristics (viability and morphology), fourteen phenotypic and agronomic, voluntary plant, vigor and germination, and over seventy observations for each plant-insect interaction, plant-disease and plant-abiotic stress were collected(41, 42). Field experiments (2008/2009 crop)(42) generated sufficient agronomic and phenotypic information for MON 88017 corn to support a conclusion that corn MON 88017, except for the characteristics introduced by the genetic modification, is not different from the control corn. The characteristics of resistance to larvae of pest-coleopteran of the Diabrotica genus and tolerance to glyphosate failed to change MON 88017 corn in a pest plant or in a plant invasive of natural habitats, since the reproductive and development characteristics of the corn were not changed(1). Therefore, corn MON 88017 in the Brazilian cultivation conditions failed to pose any environmental risk, had a potential not greater than conventional corn to change into a pest plant, and did not show an increased gene flow risk to conventional corn or sexually compatible species(1). Impact assessment in usual agronomic practices indicated that MON 88017 corn has no impact in practices of cultivation and rotation, or in the management of insects and diseases different from those caused by conventional corn, except for the control of pest coleopteran larvae of the genus Diabrotica. Use of MON 88017 corn enables, in addition, controlling a wide range of grasses and perennial large leaf pest plants through application in post-emergence of the glyphosate herbicide, similar to what happened with NK603 corn(1). Assessing the impact on non-target organisms is an important part of assessing environmental risk of genetically modified cultures(1). Aspects related to ecologic interactions, addressing possible impacts of MON 88017 corn in non-target organisms resulting from the release of such corn into the environment were analyzed and submitted. Several laboratory studies with indicator species that are non-target for protein Cry3Bb1 showed that protein Cry3Bb1 fails to cause adverse effects on non-target organisms tested. Protein CP4 EPSPS, in turn has a mode of action different from protein Cry3Bb1, which is not an insecticide activity against target-pests(1). Field studies conducted with genetically modified cultures resistant to insect showed that such cultures do not cause adverse effects for diversity and abundance of non-target insect communities, including predators, parasitoids and other ecologically important non-target insects(23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38). Potential adverse effects to non-target organisms resulting from exposure to changes of Cry3Bb1 protein were assessed in unnumbered studies with birds (Bobwhite quail), aquatic animals (catfish and water flea) and beneficial land invertebrate species (springtails, ladybugs, adult bees and larvae, aphis-lions, parasitoid wasps and earthworms). These non-target organisms were exposed to high doses of corn leaf tissue, pollen and kernels containing the varieties of Cry3Bb1 produced in plant and in E. coli. The results indicate that the varieties of Cry3Bb1 protein fail to cause significant risk to non-target organisms(1). Protein Cry3Bb1 produced in MON 88017 corn did not display impact in the abundance of non-target organisms(1). Abundance of prominent non-target benefic invertebrate species was commensurate in parcels planted with conventional corn and with genetically modified corns expressing protein Cry3Bb139). In the United States, ecological interactions of MON 88017 corn in field experiments (2002 crop) were studied for interactions with specific insects, diseases and stresses. Results of these assessment of ecologic interactions in the same places and years, based on monitoring of specific insects, diseases and abiotic stresses failed to show differences in susceptibility to pests or environmental stresses(1). Therefore, ecologic interaction for MON 88017 corn were not changed by genetic modification. In Brazil, ecologic interactions of MON 88017 corn were assessed during field experiments (2008/2009 crop) (1, 42). Abundance of non-target organisms was assessed in a survey of the insect fauna in fields experiments conducted in Brazil (2008/2009 crop)(42). Abundance analysis of non-target organisms, both in the air and in soil, failed to record significant differences in the vast majority of observations(1, 42). When analyzing abundance of aerial non-target organisms, it was noted that in the five observations, the results obtained for corn MON 88017 were within the abundance interval of reference materials and the variation of the response was considered natural and not associated to the genetic change on screen(1). When analyzing abundance of soil non-target organisms, a similar visitation (observed in parcels of MON 88017 corn, control corn and commercial references) indicated that introduction of resistance to larvae of pest coleopteran of the Diabrotica genus does not interfere with the visitation of insects assessed in the genetically modified corn(1,42). Protein Cry3Bb1 produced in MON 88017 corn is highly specific in insecticide activity against larvae of pest coleopteran of the Diabrotica genus and has display little activity against non-coleopterans(1). It is not expected that protein EP4 EPSPS cause impacts on target and non-target organisms, since the characteristic is related to the herbicide applied in controlling pest plants rather than insects(1). Soil organisms may be exposed to Cry3Bb1 protein through contact with the roots, with cultural residues in the soil or with the pollen deposited in the soil(1). Studies showed that Cry proteins do not possess in vitro microbicide or microbiostatic activity against bacteria, fungi and algae(44) and that root exudates and biomass of Bt corn have no apparent effect on earthworms, nematodes, protozoa, bacteria and fungi(45) In Brazil, an assessment of bacteria, fungi and actinomices colony forming units (CFU) in soil samples collected in four different locations of representative areas in the production of corn (2008/2009 crop) (1, 43). There was no record of significant differences between the results of MON 88017 corn and the control corn for the most probable number of bacteria, fungi and actinomices colony forming units(1, 43). Regarding environmental safety, the results of phenotypic and agronomic assessments conducted in Brazil corroborated the United States data, indicating that MON 88017 corn has no characteristics that may pose a significantly changes risk of a plant becoming a pest plant or causing an ecologic impact different from conventional corn(1). Besides, data on ecologic interaction indicate that MON 88017 corn fails to grant any greater susceptibility of tolerance to diseases, abiotic stresses or insects besides those controlled by the resistance characteristic introduced in the plant. Taken as a whole, the data show that corn MON 88017 fails to pose a risk to the environment when compared to the conventional corn. Field efficacy of corn MON 88017 against Diabrotic larvae assessed in both the United States and Brazil support the conclusion that protein Cry3Bb1 produced in corn MON 88017 provides significant control of Diabrotica larvae that feed on corn roots(1). It shall be stressed that corn MON 88017 is currently approved in the United States, (2005), Japan (2006), Mexico (2006), Canada (2006), Australia (2006), South Korea (2006), Philippines (2006), Taiwan (2006), China (2007) and the European Union (2009) and, up to this moment, requests for commercial release of corn MON 88017 have not been turned down in any country. VI. Restrictions to the Use of the GMO and GMO Derivatives According to Article 1 of Law no. 11,460, of March 21, 2007, “research and cultivation of genetically modified organisms are forbidden in indigenous and Conservation Unit areas”. VII. Considerations on Particulars from Different Regions of the Country (Subsidies to Monitoring Bodies) According to Article 1 of Law no. 11,460, of March 21, 2007, “research and cultivation of genetically modified organisms are forbidden in indigenous and Conservation Unit areas”. VIII. Conclusion Considering that the corn variety MON 88017 belongs to the species Zea mays L., well characterized and featuring a solid history of safety for human and animal consumption, and taking in consideration that the genes cp4 epsps and cry3Bb1 inserted in this variety code proteins that are ubiquitous in nature, present in plants, fungi and microorganisms, which also have a large history of safe use for humans and animals; Considering that the construct of this event occurred through recombinant DNA techniques resulting in the heritage of a stable and functional copy of genes cry3Bb1 and cp4 epsps that granted resistance to insects and tolerance to the herbicide glyphosate; Considering that centesimal composition data failed to record any significant difference between the genetically modified corn (MON 88017) and conventional corn varieties, suggesting nutritional equivalence between them; and Whereas: 1. Event MON 88017 is molecularly characterized and integrity of the inherited genetic construct was maintained: a single and intact insert, integrated in a single locus of the corn genome, with all genetic elements intact and no region of the plasmid PV-GMIR39 present in the generated transformation event; 2. There is no indication of interaction between the metabolic pathways where proteins Cry3Bb1 and CP4 EPSPS act; 3. No pleiotropic and epistatic effects were identified in MON 88017 corn; 4. Expression of proteins Cry3Bb1 and CP4 EPSPS in MON 88017 corn is not significantly different of the expression recorded in E. coli; 5. There is no indication that the newly expressed proteins may cause allergy or intoxication in humans and animals; 6. Corn MON 88017 agronomic and efficacy assessments indicate that the event failed to cause expression of any other characteristics except the expected one, to wit, resistance to insect and tolerance to the herbicide glyphosate; 7. There is no evidence of botanical changes in MON 88017 corn that may grant adaptive advantages; and 8. The remaining risk analyses conducted by countries that have already assessed corn MON 88017; the conclusion is that corn MON 88017 is as safe as its conventional equivalent. Under Article 14 of Law nº 11,105/2005, CTNBio held that the request complies with the applicable rules and legislation aimed at securing safety of the environment, agriculture, and human and animal health, and concluded that corn MON 88017 is substantially equivalent to conventional corn, being its consumption safe for human and animal health. Regarding the environment, CTNBio concluded that farming of MON 88017 corn is not a potential cause of significant degradation to the environment, keeping with the biota a relation identical to that of conventional cotton. CTNBio concluded this activity is not a potential cause of significant degradation to the environment or harm to human and animal health. Restrictions to the use of the GMO under analysis are conditioned to the provisions of Law nº 11,460, of March 21, 2007. Regarding the post-commercial release monitoring plan, CTNBio determines that the company shall follow the standard passed in the Minutes of the 135th Ordinary Meeting o CTNBio, held on August 19, 2010. Regarding the post-commercial release monitoring plan of the GMO resistant to insects and tolerant to the herbicide glyphosate, CTNBio determines that the following instructions shall be attended and conducted the monitoring techniques mentioned below: I. Instructions (a) Monitoring must be conducted in commercial and not in experimental cultures. Areas selected for monitoring shall not be separated from the others, be fenced or display any condition extraneous to the commercial standard. (b) Monitoring must be conducted in a comparative model between conventional cultivation and GMO cultivation systems, where data collection shall be made by sampling. (c) Monitoring must be conducted in biomes that are representative of the main GMO culture areas and, whenever possible, include different type of producers. (d) Monitoring must be conducted for a period of at least five years. (e) For all monitoring procedures, the applicant shall detail the data on all activities conducted in pre-sowing and sowing, on its performance, reporting all activities carried out in the monitoring area during the culture cycle, in harvesting activities and climatic conditions. (f) Any hazard to human and animal health shall be monitored through official adverse effects notification systems, such as SINEPS – Sistema de Notificação de Eventos Aversos Relacionados a Produtos de Saúde the Adverse Effects Related to Health Products Notification System as regulated by ANVISA. (g) Analytical methods, results attained and their interpretation must be developed in line with independence and transparence principles, except for commercial secrecy aspects previously justified and defined as such. (h) On technical and scientific grounds, CTNBio reserves the right to review this Opinion at any time. II. Technical Monitoring Actions to be Conducted: 1 - Regarding gene cp4 epsps, which grants resistance to the herbicide glyphosate, the following shall be monitored: (a) Nutritional state and sanity of GMO plants. (b) Chemical and physical soil attributes related to fertility and other basic edaphology characteristics. (c) Soil microbial diversity. (d) Soil dispersion bank. (e) Community of invading plants. (f) Development of resistance to herbicide in invading plants. (g) Residues of herbicide in the soil, kernels and aerial part. (h) Gene flow. 2 - Regarding gene cry3Bb1, which grants resistance to insects, the following shall be monitored: (a) Impact on target and non-target insects. (b) Impact on soil invertebrate indicators that are not under the Insecta Class. (c) Residues of insecticide proteins in the decomposing organic matter, both in the soil and watercourses near the monitoring area. (d) Development of resistance among target-insects. (e) Gene flow of the two inserted genes (transgene). CTNBio analysis took into consideration the opinions of the Commission members, ad hoc consultants, and documents delivered by applicant to the CTNBio Office of the Executive Secretary in addition to results of planned releases into the environment. Further, applicant and third parties’ independent scientific studies and publications were also taken into consideration. IX. Bibliographic References 1. Monsanto do Brasil, 2010. Relatório de Biossegurança Alimentar e Ambiental do milho MON88017, 293 pag. 2. Padgette, S.R., Re, D., Barry, G., Eichlholtz, D., Delannay, X., Fuchs, R.L. Kishore, G., Fraley, R.T. 1996. New weed control opportunities: Development of soybean with a Roundup Ready® gene. CRC Press, Boca Raton, Florida. 3. Steinrücken, H.C., e N. Amrhein. 1980. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl- shikimic acid-3-phosphate synthase. Biochem Biophys Res Commun 94:1207-1212. 4. Haslam, E. 1993. Shikimic acid: metabolism and metabolites. University of Sheffield, UK. 5. Donovan, W.P., M.J. Rupar, A.C. Slaney, T. Malvar, M.C. Gawron-Burke, e T.B. Johnson. 1992. Characterization of two genes encoding Bacillus thuringiensis insecticidal crystal proteins toxic to coleopteran species. Appl. Environ. Microbiol.58:3921-3927. 6. Romano, C.P. 2002. Expression of Cry3B insecticidal protein in plants. Unites States Patent No. 6,501,009. 7. Crickmore, N., D.R. Zeigler, J. Feitelson, E. Schnepf, J. Van Rie, D. Lereclus, J. Baum, e D.H. Daen. 1998b. Revision of the nomenclature for the Bacillus thuringiensis pesticidal crystal proteins. Microbiology and Molecular Biology Reviews 62:807-813 8. U.S. EPA. 2004b. FIFRA Scientific Advisory Panel Meeting. SAP Report no. 2004-05. Product characterization, human health risk, ecological risk, and insect resistance management for Bacillus thuringiensis (Bt) cotton products. U.S.Environmental Protection Agency. 9. ILSI-CCD. 2006. International Life Science Institute Crop Composition Database. http://www.cropcomposition.org/ Version 3.0. 10. U.S. EPA. 2001a. Biopesticides registration action document, revised risks and benefits section, Bacillus thuringiensis plant-pesticides [Online] http://www.epa.gov/pesticides/biopesticides/pips/bt_brad.htm (verified December 1, 2005). 11. McClintock, J.T., C.R. Schaffer, e R.D. Sjobald. 1995. A comparative review of the mammalian toxicity of Bacillus thuringiensis-based pesticides. Pest. Sci. 45:95-105. 12. U.S. EPA. 1996. Harmonized OPPTS testing guidelines 712-C-96-280 February 1996 as defined in 40 CRF 152.20. U.S.Environmental Protection Agency. 13. U.S. EPA. 1998. Bacillus thuringiensis (B.t.) plant-pesticides and resistance managment EPA 738-F-98-001. United States Environmental Protection Agency. 14. U.S. EPA. 2001d. Regulation under the FIFRA for plant-incorporated protectants (formerly plant-pesticides). U.S.Environmental Protection Agency Federal Register 59: 37772-6054737817. 15. Harrison, L.A., M.R. Bailey, M.W. Naylor, J.E. Ream, B.G. Hammond, D.L. Nida, B.L. Burnette, T.E. Nickson, T.A. Mitsky,M.L. Taylor, R.L. Fuchs, e S.R. Padgette. 1996. The expressed protein in glyphosate-tolerant soybean, 5-enolypyruvylshikimate-3-phosphate synthase from Agrobacterium sp. strain CP4, is rapidly digested in vitro and is not toxic to acutely gavaged mice. Journal of Nutrition 126:728-740. 16. U.S. EPA. 2004b. FIFRA Scientific Advisory Panel Meeting. SAP Report no. 2004-05. Product characterization, human health risk, ecological risk, and insect resistance management for Bacillus thuringiensis (Bt) cotton products. U.S.Environmental Protection Agency. 17. Codex. 2003. Guideline for the conduct of food safety assessment of foods derived from recombinant DNA plants.CAC/GL:45. 18. Thomas, K., M. Aalbers, G.A. Bannon, M. Bartels, R.J. Dearman, D.J. Esdaile, T.J. Fu, C.M. Glatt, N. Hadfield, C. Hatzos,S.L. Hefle, J.R. Heylings, R.E. Goodman, B. Henry, C. Herouet, M. Holsapple, G.S. Ladics, T.D. Landry, S.C.MacIntosh, E.A. Rice, L.S. Privalle, H.Y. Steiner, R. Teshima, R. Van Ree, M. Woolhiser, e J. Zawodny. 2004. A multilaboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins. Regul.Toxicol. Pharmacol. 39:87-98. 19. Luna, V., J.M. Figueroa, B.M. Baltazar, R.L. Gomez, R. Townsend, e J.B. Schoper. 2001. Maize pollen longevity and distance isolation requirement for effective pollen control. Crop Sci. 41. 20. Bannert, M. 2006. Simulation of transgenic pollen dispersal by use of different grain colour maize. Doctor of Sciences Dissertation. Swiss Federal Institute of Technology Zurich. Diss. ETH No. 16508. 21. Rosenbaum, E.W., C.C. Wilste, e M.J. Horak. 2003. Phenotypic and ecological observations of MON 88017 corn in 2001 U.S. field trials for an assessment of equivalence and weed potential. Monsanto Technical Report MSL 17652. 22. Pester, T.A., e C.L. Woodrum. 2003. Phenotypic and ecological observations of MON 88017 corn in U.S. field trials during 2002 for an assessment of equivalence and weed potential. Monsanto Technical Report MSL 18944. 23. Bhatti, M., J. Duan, G. Head, C. Jiang, M. McKee, T. Nickson, C. Pilcher, e C. Pilcher. 2005a. Field evaluation of the impact of corn rootworm (Coleoptera: Chrysomelidae)-protected Bt corn on ground-dwelling invertebrates. Environ.Entomol. 34:1325-1335. 24. Bitzer, R., M. Rice, C. Pilcher, C. Pilcher, e W.-k.f. Lam. 2005. Biodiversity and community structure of epedaphic and euedaphic springtails (Collembola) in transgenic rootworm Bt corn. Environ. Entomol. 34:1346-1375. 25. Daly, T., e G.D. Buntin. 2005. Effect of Bacillus thuringiensis Transgenic Corn for Lepidopteran Control on Nontarget Arthropods. Environ. Entomol. 34:1292-1301. 26. Dively, G.P. 2005. Impact of Transgenic VIP3A x Cry1Ab Lepidopteran-resistant Field Corn on the Nontarget Arthropod Community. Environ. Entomol. 34:1267-1291. 27. Head, G., W. Moar, M. Eubanks, B. Freeman, J. Ruberson, A. Hagerty, e S. Turnipseed. 2005. A multiyear, large-scale comparison of arthropod populations on commercially managed Bt and non-Bt cotton fields. Environ. Entomol.34:1257-1266. 28. Lopez, M.D., J.R. Prasifka, D.J. Bruck, e L.C. Lewis. 2005. Utility of Ground Beetle Species in Field Tests of Potential Nontarget Effects of Bt Crops. Environ. Entomol. 34:1317-1324. 29. Lozzia, G., C. Furlanis, B. Manachini, e L. Rigamonti. 1998. Effects of Bt corn on Rhopalosiphum padi L. (Rhynchota Aphididae) and on its predator Chrysoperla carnea Stephen (Neuroptera Chrysopidae). Boll. Zool. Agraria Bachicol. 30:153-164. 30. Naranjo, S., G. Head, e G. Dively. 2005a. Special section introduction: field studies assessing arthropod non-target effects in Bt transgenic crops. Environ. Entomol. 34:1178-1180. 31. Naranjo, S., G. Head, e G. Dively. 2005b. Field studies assessing arthropod non-target effects in Bt transgenic crops: Introduction. Environ. Entomol. 34:1178-1180. 32. Orr, D.R., e D.A. Landis. 1997. Oviposition of European corn borer (Lepidoptera: Pyralidae) and impact of natural enemy populations in transgenic versus isogenic corn. J. Econ. Entomol. 90:905-909. 33. Pilcher, C.D., M.E. Rice, e J.J. Obrycki. 2005. Impact of Transgenic Bacillus thuringiensis Corn and Crop Phenology on Five Nontarget Arthropods. Environ. Entomol. 34:1302-1316. 34. Pilcher, C.D., J.J. Obrycki, M.E. Rice, e L.C. Lewis. 1997. Preimaginal development, survival and field abundance of insect predators on transgenic Bacillus thuringiensis Corn. Biological Control 26:446-454. 35. Romeis, J., A.M. Shelton, e G. Kennedy. 2008a. Integration of insect-resistant genetically modified crops within IPM programs (Progress in biological control) Springer; 1 edition (Aug 1, 2008). 36. Torres, J.B., e J.R. Ruberson. 2005. Canopy- and ground-dwelling predatory arthropods in commercial Bt and non-Bt cotton fields: patterns and mechanisms. Environ. Entomol. 34:1242-1256. 37. Whitehouse, M., L. Wilson, e G. Fitt. 2005. A comparison of arthropod communities in transgenic Bt and conventional cotton in Australia. Environ. Entomol. 34:1224-1241 38. Wolfenbarger, L.L., S.E. Naranjo, J.G. Lundgren, R.J. Bitzer, e L.S. Watrud. 2008. Bt crops effects on functional guilds ofnon-target arthropods: a meta-analysis. PLOS One 3(5): e2118. 11p. 39. U.S. EPA. 2003. Biopesticide registration action document: event MON 863 Bacillus thuringiensis Cry3Bb1 corn. 40. Oliveira, W.S. 2009. Produção de tecido vegetal de milho geneticamente modificado resistente a insetos MON 88017 e milho convencional em ambiente natural para subsequentes análises. Relatório interno da Monsanto. MSP021. 41. Oliveira, W.S. 2010a. Avaliação do vigor e germinação de grãos de milho geneticamente modificado resistente a insetos MON 88017, milho geneticamente modificado resistente a insetos e tolerante ao glifosato MON 88017 × MON 89034, milho convencional e referência. Relatório interno da Monsanto. MSP-041. 42. Oliveira, W.S. 2010b. Observações fenotípicas, interações ecológicas e avaliação de organismos não alvo em área cultivada com milho geneticamente modificado resistente a insetos e tolerante ao glifosato MON 88017, milho geneticamente modificado resistente a insetos e tolerante ao glifosato MON 88017 × MON 89034 e milho convencional em ambiente natural. Relatório interno da Monsanto. MSP-033. 43. Oliveira, W.S. 2010d. Avaliação do efeito do milho geneticamente modificado resistente a insetos MON 88017, milho geneticamente modificado resistente a insetos e tolerante ao glifosato MON 88017 × MON 89034 e milho convencional sobre o número de microrganismos do solo em ambiente natural. Relatório interno da Monsanto. MSP-042. 44. Koskella, J., e G. Stotzky. 2002. Larvicidal toxins from Bacillus thuringiensis subspp. kurstaki, morrisoni (strain tenebrionsis), and israelensis have no microbiocidal or microbiostatic activity against selected bacteria, fungi, and algae in vitro. Can. J. Microbiol. 48:262-267. 45. Saxena, D., e G. Stotzky. 2001. Bacillus thuringiensis (Bt) toxin released from root exudates and biomass of Bt corn has no apparent effect on earthworms, nematodes, protozoa, bacteria, and fungi in soil. Soil Biol. and Biochem. 33:1225-1230. Brasília, December 16, 2010
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Where detection method protocols and appropriate reference material (non-viable, or in certain circumstances, viable) suitable for low-level situation may be obtained:
Molecular traditional methods
Relevant links to documents and information prepared by the competent authority responsible for the safety assessment: National Biosafety Commission
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E-mail:
gutemberg.sousa@mcti.gov.br
Organization/agency name (Full name):
National Biosafety Technical Commission
Contact person name:
Edivaldo Domingues Velini
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SPO Area 5 Qd 3 Bl B S 10.1 Brasilia DF
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556133177475
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The Brazilian National Biosafety Commission – CTNBio , is responsible to the technical decision on biological risk as a response to a request from the proponent. The technical decision is given on a definitive basis. Only the National Biosafety Council (CNBS) can revoke the decision (in case of commercial release), based on social-economical reasons and not on biosafety reasons. Once a decision is taken by CTNBio favorable to the commercial release of a new GMO (being it a plant or any other organism), CNBS has 30 days to issue a revoke. After these steps, the new product must be evaluated for conformity to the Brazilian standards by the registration and enforcement agencies (ANVISA – Ministry of Health, Ministry of Agriculture, Ministry of Environment and Ministry of Fisheries, according to the intended use of the product). If it conforms to the standards, it may be offered to the market. Every institution dealing with GMOs (including universities and public research institutes) has to have an Internal Biosafety Commission (CIBio), which is legally responsible of everything that may happen to be done or caused by the GMO
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Stacked events:
At the discretion of, and upon consultation with, CTNBio, a new analysis and issuance of technical opinion may be released on GMOs containing more than one event, combined through classic genetic improvement and which have been previously approved for commercial release by CTNBio
Contact details of the competent authority(s) responsible for the safety assessment and the product applicant:
Dr. Edivaldo Domingues Velini (President of national Biosafety Commission)
Canada
Name of product applicant: Monsanto Canada Inc.
Summary of application:
Monsanto has developed corn (Zea mays) lines based upon transformation event MON 88017. Corn plants containing this vector-stacked1 trait event express two novel proteins: the CP4 5-enolpyruvylshikimate-3-phosphate (CP4 EPSPS) protein which confers tolerance to glyphosate herbicides (many marketed as Roundup® brand), and the Cry3Bb1 protein which exhibits insecticidal activity against certain Coleopteran pests such as corn rootworms (Diabrotica sp.).

Health Canada has previously indicated no objection to the sale of the single trait Roundup Ready® corn event NK-603 expressing the CP4 EPSPS enzyme for human food applications. Health Canada has also previously indicated no objection to the sale of the single trait YieldGard® Rootworm corn event MON 863 expressing a variant of the Cry3Bb1 protein for human food applications.

The safety assessment performed by Food Directorate evaluators was conducted according to Health Canada's Guidelines for the Safety Assessment of Novel Foods. The assessment considered: how corn event MON 88017 was developed; how the composition and nutritional quality of corn grain derived from plants containing this event compare to non-modified corn; and what the potential is for food products derived from plants containing this event to be toxic or cause allergic reactions.

The Food Directorate has a legislated responsibility for 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). Foods derived from corn lines containing event MON 88017 are considered novel foods 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

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

1. Vector-stacked traits are derived from a single insertion of two tandem gene expression cassettes into the plant genome, differing from conventional stacked traits, which are derived by cross-breeding of two single trait lines.

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Date of authorization: 17/02/2006
Scope of authorization: Food and feed
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Please see decision document weblinks
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Novel Feeds Decision
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luc.bourbonniere@hc-sc.gc.ca
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Health Canada
Contact person name:
Luc Bourbonniere
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251 Sir Frederick Banting Driveway, Tunney's Pasture, PL 2204A1
Phone number:
613-957-1405
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613-952-6400
Country introduction:
Federal responsibility for the regulations dealing with foods sold in Canada, including novel foods, is shared by Health Canada and the Canadian Food Inspection Agency (CFIA). Health Canada is responsible for establishing standards and policies governing the safety and nutritional quality of foods and developing labelling policies related to health and nutrition. The CFIA develops standards related to the packaging, labelling and advertising of foods, and handles all inspection and enforcement duties. The CFIA also has responsibility for the regulation of seeds, veterinary biologics, fertilizers and livestock feeds. More specifically, CFIA is responsible for the regulations and guidelines dealing with cultivating plants with novel traits and dealing with livestock feeds and for conducting the respective safety assessments, whereas Health Canada is responsible for the regulations and guidelines pertaining to novel foods and for conducting safety assessments of novel foods. The mechanism by which Health Canada controls the sale of novel foods in Canada is the mandatory pre-market notification requirement as set out in Division 28 of Part B of the Food and Drug Regulations (see Figure 1). Manufacturers or importers are required under these regulations to submit information to Health Canada regarding the product in question so that a determination can be made with respect to the product's safety prior to sale. The safety criteria for the assessment of novel foods outlined in the current document were derived from internationally established scientific principles and guidelines developed through the work of the Organization for Economic Cooperation and Development (OECD), Food and Agriculture Organisation (FAO), World Health Organisation (WHO) and the Codex Alimentarius Commission. These guidelines provide for both the rigour and the flexibility required to determine the need for notification and to conduct the safety assessment of the broad range of food products being developed. This flexibility is needed to allow novel foods and food products to be assessed on a case-by-case basis and to take into consideration future scientific advances.
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Stacked events:
Food: Consistent with the definition of "novel food" in Division 28 of the Food and Drug Regulations, the progeny derived from the conventional breeding of approved genetically modified plants (one or both parents are genetically modified) would not be classified as a novel food unless some form of novelty was introduced into such progeny as a result of the cross, hence triggering the requirement for pre-market notification under Division 28. For example, notification may be required for modifications observed in the progeny that result in a change of existing characteristics of the plant that places those characteristics outside of the accepted range, or, that introduce new characteristics not previously observed in that plant (e.g. a major change has occurred in the expression levels of traits when stacked). In addition, the use of a wild species (interspecific cross) not having a history of safe use in the food supply in the development of a new plant line may also require notification to Health Canada. However, molecular stacks are considered new events and are considered to be notifiable as per Division 28.

Feed:
Contact details of the competent authority(s) responsible for the safety assessment and the product applicant:
Luc Bourbonniere, Section Head Novel Foods
Philippines
Name of product applicant: Monsanto Philippines
Summary of application:
Corn MON 88017 plants produce the CP4 5-enolpyruvylshikimate-3-phospate synthase protein (CP4 EPSPS) derived from Agrobacterium strain CP4 providing tolerance to glyphosate and a modified Bacillus thuringiensis subsp. kumamotoensis Cry3Bb1 protein that selectively controls Diabrotica spp.. The CP4 EPSPS is naturally less sensitive to inhibition by glyphosate and has been shown to impart tolerance to glyphosate in several crops.
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Date of authorization: 21/03/2011
Scope of authorization: Food and feed
Links to the information on the same product in other databases maintained by relevant international organizations, as appropriate. (We recommend providing links to only those databases to which your country has officially contributed.):
Summary of the safety assessment:
Monsanto Philippines Inc. submitted an application to the Bureau of Plant Industry (BPI) requesting for biosafety permit under AO#8 part 5 for Corn MON 88017 which has been genetically modified for insect resistance and herbicide tolerance. Corn MON 88017 has been evaluated according to safety assessment by concerned agencies of the Department of Agriculture, such as the Bureau of Animal Industry (BAI) for feed safety, and Bureau of Fisheries and Product Standards (BAFPS) for food safety, and a Scientific Technical Review Panel (STRP) members. The process involves an intensive analysis of the nature of the genetic modification together with a consideration of general safety issues which includes molecular characterization, protein characterization, toxicological, allergenicity and nutritional issues and food/feed comparison. The petitioner/applicant published the Public Information Sheet (PIS) of the said application in two widely circulated newspapers for public comment/review. BPI received no comment on the petition during the 30-day comment period. Review of results of evaluation by the BPI Biotech Core Team completed the approval process.
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Where detection method protocols and appropriate reference material (non-viable, or in certain circumstances, viable) suitable for low-level situation may be obtained:
Relevant links to documents and information prepared by the competent authority responsible for the safety assessment:
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Authorization expiration date:
E-mail:
bpibiotechsecretariat@yahoo.com
Organization/agency name (Full name):
Bureau of Plant Industry
Contact person name:
Thelma L. Soriano
Website:
Physical full address:
San Andres St., Malate, Manila
Phone number:
632 521 1080
Fax number:
632 521 1080
Country introduction:
The Philippines is the first ASEAN country to establish a modern regulatory system for modern biotechnology. The country's biosafety regulatory system follows strict scientific standards and has become a model for member-countries of the ASEAN seeking to become producers of agricultural biotechnology crops. Concerns on biosafety in the Philippines started as early as 1987 when scientists from the University of the Philippines Los Banos (UPLB) and International Rice Research Institute (IRRI), the Quarantine Officer of the Bureau of Plant Industry (BPI) and the Director for Crops of the Philippine Council for Agriculture, Forestry and Natural Resources Research and Development (PCARRD) recognized the potential for harm of the introduction of exotic species and genetic engineering. The joint committee formed the biosafety protocols and guidelines for genetic engineering and related research activities for UPLB and IRRI researchers. This proposal was eventually adapted into a Philippine Biosafety policy by virtue of Executive Order No 430, Series of 1990, issued by then President Corazon C. Aquino on October 15, 1990, which created the National Committee on Biosafety of the Philippines (NCBP). The NCBP formulates, reviews and amends national policy on biosafety and formulates guidelines on the conduct of activities on genetic engineering. The NCBP comprised of representative from the Department of Agriculture (DA); Department of Environment and Natural Resources (DENR); Health (DOH); and Department of Science and Technology (DOST), 4 scientists in biology, environmental science, social science and physical science and 2 respected members of the community. The Philippines’ Law, Executive Order No.514 (EO514), Series of 2006 entitled “Establishing the National Biosafety Framework (NBF), Prescribing Guidelines for its Implementation, Strengthening the National Committee on Biosafety of the Philippines, and for Other Purposes was also issued. This order sets the establishment of the departmental biosafety committees in the DA, DENR, DOH and DOST. The mandates jurisdiction and other powers of all departments and agencies in relation to biosafety and biotechnology is guided by the NBF in coordination with the NCBP and each other in exercising its power. The Department of Agriculture (DA) issued Administrative Order No 8, Series of 2002, (DA AO8, 2002), which is part of EO 514, for the implementation of guidelines for the importation and release into the environment of plants and plant products derived from the use of modern biotechnology. The DA authorizes the Bureau of Plant Industry (BPI) as the lead agency responsible for the regulation of agricultural crops developed through modern biotechnology. The BPI has adopted a protocol for risk assessment of GM crops for food and feed or for processing based on the Codex Alimentarius Commission’s Guideline for the Conduct of Food Safety assessment of Foods Derived from Recombinant-DNA plants and a protocol for environmental risk assessment in accordance with the Cartagena Protocol on Biosafety and with the recommendation of the Panel of Experts of the Organization for Economic Cooperation and Development (OECD). DA AO8, 2002 ensures that only genetically food crops that have been well studied and found safe by parallel independent assessments by a team of Filipino scientists and technical personnel from the concerned regulatory agencies of the Department are allowed into our food supply and into our environment. The DA AO 8, 2002 has a step by step introduction of GM plant into the environment. The research and development phase would require testing the genetically modified (GM) crop under controlled conditions subject to regulation by the government agencies. The first stage of evaluation for GM crops is testing under contained facilities such as laboratories, greenhouses and screenhouses. After satisfactory completion of testing under contained facilities, confined environmental release or field trial is done. Confined field trial (CFT) is the first controlled introduction of the GM crop into the environment. The approval for field trial shall be based on the satisfactory completion of safety testing under contained conditions. Unconfined environmental release or commercialization of the product would follow after the safe conduct of the CFT. Approval for propagation shall only be allowed after field trials and risk assessment show no significant risk to human and animal health and the environment.
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Relevant documents
Stacked events:
Gene stacking in plants can be conferred either through genetic engineering or conventional breeding A full risk assessment as to food and feed or for processing shall be conducted to plant products carrying stacked genes conferred through genetic engineering or conventional breeding, where the individual traits have no prior approval for direct use as food and feed or processing from the Bureau of Plant Industry (BPI) A desktop or documentary risk assessment on the possible or expected interactions between the genes shall be conducted for stacked gene products with multiple traits conferred through conventional breeding and individual events granted prior approval by the Bureau of Plant Industry.
Contact details of the competent authority(s) responsible for the safety assessment and the product applicant:
Bureau of Plant Industry 692 San Andres St, Malate, Manila 1004