GM Crop Database

Database Product Description

MON802 (MON-80200-7)
Host Organism
Zea mays (Maize)
Trade Name
Yieldgard®
Trait
Resistance to European corn borer (Ostrinia nubilalis); glyphosate herbicide tolerance.
Trait Introduction
Microparticle bombardment of plant cells or tissue
Proposed Use

Production for human consumption and livestock feed.

Product Developer
Monsanto Company

Summary of Regulatory Approvals

Country Food Feed Environment Notes
Canada 1997 1997 1997
United States 1996 1996 1997

Introduction Expand

Maize line MON802 was developed through a specific genetic modification to be resistant to attack by European corn borer (ECB; Ostrinia nubilalis), a major insect pest of maize in agriculture. The novel variety produced the insecticidal protein, Cry1Ab, derived from Bacillus thuringiensis subsp. kurstaki (B.t.k.) HD-1 strain. Delta-endotoxins, such as the Cry1Ab protein expressed in MON802, act by selectively binding to specific sites localized on the brush border midgut epithelium of susceptible insect species. Following binding, cation-specific pores are formed that disrupt midgut ion flow and thereby cause gut paralysis and eventual death due to bacterial sepsis. Cry1Ab is insecticidal only to lepidopteran insects, 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 delta-endotoxins of B. thuringiensis on the surface of mammalian intestinal cells, therefore, livestock animals and humans are not susceptible to these proteins.

In addition, two novel genes were introduced into maize line MON802, which in combination provide field level tolerance to glyphosate the active ingredient in Roundup® herbicide. The novel plants express a glyphosate tolerant version of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) encoding gene isolated from Agrobacterium tumefaciens strain CP4 (CP4 EPSPS). Glyphosate specifically binds to and inactivates EPSPS, which is involved in the biosythesis of the aromatic amino acids tyrosine, phenylalanine and tryptophan. The EPSPS enzyme is present in all plants, bacteria and fungi, but not in animals, which do not synthesize their own aromatic amino acids. The modified enzyme (CP4 EPSPS) has a reduced binding affinity for glyphosate and allows the plant to function normally in the presence of the herbicide.

The second gene codes for glyphosate oxidase (gox gene), a bacterial enzyme from Ochrobactrum anthropi and is ubiquitous in nature. Glyphosate oxidase (GOX) accelerates the normal degradation of glyphosate into aminomethylphosphonic acid (AMPA) and glyoxylate. AMPA is the principal metabolite of glyphosate and is degraded by several microorganisms while glyoxylate is commonly found in plant cells and is broken down by the glyoxylic pathway for lipid metabolism.

Summary of Introduced Genetic Elements Expand

Code Name Type Promoter, other Terminator Copies Form
cry1Ab Cry1Ab delta-endotoxin (Btk HD-1) IR enhanced CaMV 35S A. tumefaciens nopaline synthase (nos) 3'-untranslated region 1 full length, 2 partial Truncated, modified; Located within first insertion site
CP4 epsps 5-enolpyruvyl shikimate-3-phosphate synthase HT enhanced CaMV 35S, HSP70 intron, gox cassette chloroplast transit peptide from A. thaliana EPSPS gene (CTP2) 1 Located within first insertion site
goxv247 glyphosate oxidoreductase HT chloroplast transit peptide from A. thaliana SSU1A gene (CTP1) 2+1 2 full length copies at first insertion site, 1 and second site
nptII neomycin phosphotransferase II SM 2 Not expressed in plant tissues; 1 copy at each insertion site

Characteristics of Zea mays (Maize) Expand

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 Expand

Latin Name Gene Pathogenicity
Bacillus thuringiensis subsp. kurstaki EC2.4.2.19

While target insects are susceptible to oral doses of Bt proteins, no evidence of toxic effects in laboratory mammals or birds given up to 10 µg protein/g body weight.

Agrobacterium tumefaciens strain CP4 CP4 epsps

Agrobacterium tumefaciens is a common soil bacterium that is responsible for causing crown gall disease in susceptible plants. There have been no reports of adverse effects on humans or animals.

Modification Method Expand

Maize line MON802 was produced by biolistic transformation with a mixture of DNAs from two plasmids, PV-ZMBK15 and PV-ZMGT03. Plasmid PV-ZMBK15 contained the synthetic cry1Ab gene regulated by the 35S promoter from cauliflower mosaic virus (CaMV) and the 3'-polyadenylation signal from the Agrobacterium tumefaciens nopaline synthase (nos) gene.

Plasmid PV-ZMGT03 contained both the CP4 EPSPS encoding gene from A. tumefaciens strain CP4 and the goxv247 gene from Ochrobactrum anthropi, which encodes the enzyme glyphosate oxidoreductase. The expression of CP4 EPSPS was regulated via the CaMV 35S promoter and the HSP70 intron, while gox gene expression was under the control of the CaMV 35S promoter only. Both genes were terminated with sequences from the 3'-polyadenylation signal from the nos gene from A. tumefaciens. Post-translational targeting of the CP4 EPSPS and glyphosate oxidoreductase enzymes to the chloroplast was accomplished by fusion of the 5'-terminal coding sequences with chloroplast transit peptide DNA sequences from Arabidopsis thaliana EPSPS gene (CTP2) and from A. thaliana SSU1A gene (CTP1), respectively.

Both plasmids also contained sequences encoding the enzyme neomycin phosphotransferase II (NPTII) from the Tn5 transposon of Escherichia coli, strain K12. Expression of the neo gene was regulated by a bacterial promoter and used as a selectable marker to identify bacteria transformed with recombinant plasmid DNAs, but is not functional in plants. The expression of CP4 EPSPS and glyphosate oxidoreductase activity were used as selectable traits to screen transformed plants for the presence of the cry1Ab gene and to confer resistance to glyphosate herbicides.

Characteristics of the Modification Expand

The Introduced DNA

Analysis of MON802 genomic DNA by Southern blotting indicated that there were two sites of integration of the introduced DNA, with the first site containing a single full length copy of the cry1Ab, CP4 EPSPS, and neo genes, two full length copies of the gox gene, and two partial copies of the cry1Ab gene. The second site contained only the gox and neo gene sequences.

Genetic Stability of the Introduced Trait

Data from successive generations of backcrosses indicated that both sites of integration segregated as a single locus and according to the rules of Mendelian inheritance.

The traits have remained stable for six generations as shown by assays for Cry1Ab, and herbicide tolerance.

Expressed Material

The expression of the Cry1Ab protein was quantitated by enzyme linked immunosorbent assay (ELISA) of tissue samples obtained from plants grown at a number of field trial locations. The average Cry1Ab concentrations were: 9.55 µg/g fresh weight (fwt) from leaf tissue (6 locations); 1.35 µg/g fwt from whole plant matter (2 locations); and 3.2 µg/g fwt from grain (6 locations).

Similarly, expressed CP4 EPSPS protein concentrations were: 26.99 µg/g fwt from leaf tissue; 1.85 µg/g fwt from whole plant tissue; and 2.27 µg/g fwt from grain. The average concentrations of GOX protein were: 10.18 µg/g fwt from leaf tissue; 1.68 µg/g fwt from whole plant tissue; and undetectable in grain.

The Cry1Ab protein was shown to degrade readily in the environment. The plant expressed protein had DT50 and DT90 values (time to degrade to 50% and 90% of the original bioactivity) of 1.6 and 15 days respectively.

Environmental Safety Considerations Expand

Field Testing

MON802 maize has been field tested since 1993 in the major maize growing regions of the United States and Puerto Rico, as well as in Canada (1995, 1996), Chile, Argentina, France, Italy, South Africa, and Costa Rica. The studies demonstrated that MON802 maize retained the agronomic characteristics of the parental line. The transgenic line provided significant protection from feeding damage from ECB throughout the season, while some protection was noted from Southwestern corn borer (Diatraea grandiosella) and corn earworm (Heliothis zea). No significant differences were observed in resistance to a number of other significant insect pests or diseases compared to non-transgenic controls. Overall the field data reports and data on agronomic traits showed that MON802 lines have no potential to pose a plant pest risk.

Outcrossing

Since pollen production and viability were unchanged by the genetic modification resulting in maize line MON802, pollen dispersal by wind and outcrossing frequency should be no different than for other maize varieties. Gene exchange between MON802 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 few plant species closely-related to maize in the wild, the risk of gene flow to other species is remote. Cultivated maize, Zea mays L. subsp. mays, is sexually compatible with other members of the genus Zea, and to a much lesser degree with members of the genus Tripsacum. However, none of the sexually compatible relatives of maize in the U.S. are considered to be weeds in the U.S., therefore it is unlikely that introgression of the CP4 EPSPS gene would provide a selective advantage to these populations as they would not be routinely subject to herbicide treatments.

Weediness Potential

No competitive advantage was conferred to MON802, other than that conferred by resistance to ECB and tolerance to glyphosate herbicide, which will not, in itself, render maize weedy or invasive of natural habitats since none of the reproductive or growth characteristics were modified.

Cultivated maize is unlikely to establish in non-cropped habitats and there have been no reports of maize surviving as a weed. In agriculture, maize volunteers are not uncommon but are easily controlled by mechanical means or by using herbicides that are not based on glyphosate. Zea mays is not invasive and is a weak competitor with very limited seed dispersal.

Secondary and Non-Target Adverse Effects

MON802 maize and the Cry1Ab protein, in particular, should not have a significant potential to harm organisms beneficial to agricultural ecosystems. The history of use and literature suggest that the bacterial Bt protein is not toxic to humans, other vertebrates, and beneficial insects. Most insecticidal protein toxins from B. thuringiensis subspecies kurstaki, including Cry1Ab, have been shown to be very selective for lepidopteran insects. Dietary toxicity studies on the effect of the microbial B.t.k. protein on non-target insects, including pollinators (honeybees), predaceous insects (green lacewing larvae, ladybird beetles) and parasitic Hymenoptera demonstrated that there was no discernible effect at approximately 10 times the usual LC50 dose for a target insect. Furthermore, MON802 will not impact on threatened or endangered lepidopteran species, as none are listed which feed on maize plants in the United States or Canada. In addition, these organisms are also not expected to be affected by the CP4 EPSPS or gox gene products.

Impact on Biodiversity

MON802 has no novel phenotypic characteristics that would extend its use beyond the current geographic range of maize production. Since the risk of outcrossing with wild relatives in the United States and Canada is remote, it was determined that the risk of transferring genetic traits from MON802 maize to species in unmanaged environments was not significant.

Other Considerations

In order to prolong the effectiveness of plant-expressed Bt toxins, and the microbial spray formulations of these same toxins, regulatory authorities in Canada and U.S. have required developers to implement specific Insect Resistant Management (IRM) Programs. These programs are mandatory for all transgenic Bt-expressing plants, including MON802 maize, and require that growers plant a certain percentage of their acreage to non-transgenic varieties in order to reduce the potential for selecting Bt-resistant insect populations. Details on the specific design and requirements of individual IRM programs are published by the relevant regulatory authority.

MON802 maize plants are not likely to eliminate the use of chemical insecticides which are traditionally applied to about 25 to 35% of the total maize acreage planted, since the primary target for most of these applications has been the coleopteran, corn rootworm. MON802 maize may positively impact current agricultural practices used for insect control by 1) offering an alternative method for control of ECB (and potentially other Cry1Ab-susceptible pests of maize); 2) reducing the use of insecticides to control European corn borer and the resulting potential adverse effects of such insecticides on beneficial insects, farm worker safety, and ground water contamination; and 3) offering a new tool for managing insects that have become resistant to other insecticides currently used or expressed in maize, including other Bt-based insecticides.

Consideration was given as to whether the introduction of crops tolerant to glyphosate would result in a significant increase in the use of the herbicide, and lead to the evolution of glyphosate resistant weeds. It was determined that the risk of increasing the selection of glyphosate tolerant weeds was low and could be mitigated through the use of other approved herbicides with a mode of action dissimilar to glyphosate. It was concluded that there was unlikely to be any significant adverse impact on agricultural practices associated with the use of the MON802 maize line.

Food and/or Feed Safety Considerations Expand

Dietary Exposure

MON802 maize was intended mainly for use in animal feed. The major human food uses for maize are extensively processed starch and oil fractions prepared by wet or dry milling procedures and products include corn syrup and corn oil, neither containing protein. Human exposure to the modified protein from whole grain corn in the diet was considered to be very low due both to its low abundance in the protein fraction of the grain and to the proportionately low percentage of protein in the kernal, compared with the major starch component. Overall, the dietary exposure of consumers in the United States and Canada to grain from MON802 maize was anticipated to be the same as for other lines of commercially available field corn.

Nutritional Data

The major components of corn grain and forage for MON802 maize were analysed on plant material harvested from field trials. Compositional data for protein, fat, ash, carbohydrates, calories, moisture, amino acids, and fatty acids for line MON802 grain were comparable to the data from the control line and within published ranges for commercial hybrids. Similar promximate analysis, including acid detergent fibre and neutral detergent fibre analyses, were performed on forage for line MON802 and an appropriate control. Based on these compositional data, it was concluded that there were no significant differences between the forage from line MON802 and the control line.

Toxicity

The low potential for toxicity of plant expressed Cry1Ab protein, and CP4 EPSPS and glyphosate oxidoreductase enzymes was demonstrated by studies on protein characterization, high oral dose feeding studies in laboratory animals, and a lack of amino acid sequence homologies with known protein toxins.

Data were generated that demonstrated that the active Cry1Ab protein product of the inserted cry1Ab gene was equivalent to that produced in the naturally occurring bacterium Bacillus thuringiensis that have been in use for over 40 years as a commercial biopesticide. The inserted, plant expressed cry1Ab gene codes for a full length protein of 1156 amino acids which is processed by proteases into the 600 amino acid tryptic core fragment which is insecticidally active. After activation by trypsin to the insecticidal form, the resulting proteolytic fragments were compared to the bacterial proteins and shown to be of similar molecular weight, immunological reactivity and trypsin resistance. The protein was not glycosylated and showed similar bioactivity and host range specificity to the native protein.

An acute oral toxicity study in mice was used to assess the potential mammalian toxicity of Cry1Ab, CP4 EPSPS and GOX proteins. There were no indications of toxicity as measured by the absence of treatment related adverse effects.
A comparison of amino acid sequences showed that the Cry1Ab protein did not show meaningful homology with the sequences of known toxin or allergens contained in the public domain databases GenBank, EMBL, Pir and SwissProt.
Similarly, the CP4 and GOX proteins did not show meaningful amino acid sequence homology when compared to known allergens or protein toxins. The Roundup Ready® proteins showed no significant homology with any known toxins or allergens. EPSPS is an enzyme that is ubiquitous in nature, and therefore would not be expected to be toxic or allergenic. For the second novel enzyme, glyphosate oxidase, experiments demonstrated that the enzyme displayed a narrow substrate specificity, and appeared not to affect any plant specific pathways.

Allergenicity

The likelihood of the Cry1Ab, CP4 EPSPS and GOX proteins being allergens was judged to be remote. No homologies were found when the deduced amino acid sequences of the introduced proteins were compared to the sequences of known allergens. In addition, the potential for allergenicity was assessed based upon the physiochemical properties of known food allergens, such as stability to acid and/or proteolytic digestion, heat stability, glycosylation, none which demonstrated characteristics normally associated with food allergens.

Protein allergens are normally resistant to digestion unlike the Cry1Ab protein that was shown to degrade readily in simulated gastric fluid. The Cry1Ab protein was rapidly degraded and its insecticidal activity lost under conditions that simulate mammalian digestion. Similarly, the enzymatic activity of CP4 EPSPS and GOX protein disappeared rapidly as these proteins were rapidly degraded under these same conditions. Both CP4 EPSPS and GOX proteins were inactivated by heat.

The Cry1Ab protein was shown to degrade readily in the environment. The plant expressed protein had DT50 and DT90 values (time to degrade to 50% and 90% of the original bioactivity) of 1.6 and 15 days respectively.
Unlike many known allergens the insecticidal protein Cry1Ab is not glycosylated. A search for amino acid sequence similarity between the Cry1Ab protein and known allergens, using a database assembled from the public domain databases GenBank, EMBL, Pir and SwissProt, revealed no significant amino acid sequence homologies.
Maize products are an important alternative to wheat flour for individuals afflicted with coeliac disease, an immune mediated food intolerance for which wheat gliadins have been implicated as the causal agent. In light of the importance of maize products to these individuals, a sequence similarity search was conducted and no amino acid sequence homologies between the Cry1Ab protein and gliadins were detected.

Abstract Collapse

Maize (Zea mays L.), or corn, is grown primarily for its kernel, which is largely refined into products used in a wide range of food, medical, and industrial goods.

Only a small amount of whole maize kernel is consumed by humans. Maize oil is extracted from the germ of the maize kernel and maize is also a raw material in the manufacture of starch. A complex refining process converts the majority of this starch into sweeteners, syrups and fermentation products, including ethanol. Refined maize products, sweeteners, starch, and oil are abundant in processed foods such as breakfast cereals, dairy goods, and chewing gum.
In the United States and Canada maize is typically used as animal feed, with roughly 70% of the crop fed to livestock, although an increasing amount is being used for the production of ethanol. The entire maize plant, the kernels, and several refined products such as glutens and steep liquor, are used in animal feeds. Silage made from the whole maize plant makes up 10-12% of the annual corn acreage, and is a major ruminant feedstuff. Livestock that feed on maize include cattle, pigs, poultry, sheep, goats, fish and companion animals.

Industrial uses for maize products include recycled paper, paints, cosmetics, pharmaceuticals and car parts.
The European corn borer (ECB), Ostrinia nubilalis, is the most damaging insect pest of maize in the United States and Canada; losses resulting from ECB damage and control costs exceed $1 billion each year. An average of one ECB cavity per maize stalk across an entire field can reduce yield by as much as 5% when caused by first generation larvae, and 2.5% when caused by second-generation larvae, with annual yield losses estimated at 5 to 10 %.

Despite consistent losses to ECB, chemical insecticides are utilized on a relatively small acreage (less than 20%). Historically, this reluctance stems from the difficulties in identifying and managing ECB in maize crops: ECB larval damage is hidden, heavy infestations are unpredictable, insecticides are costly, timing of insecticide application is difficult and multiple applications may be required to guarantee ECB control.

The transgenic maize line MON802 was genetically engineered to resist ECB by producing its own insecticide. This line was developed by introducing the cry1Ab gene, isolated from the common soil bacterium Bacillus thuringiensis (Bt), into the maize line by particle acceleration (biolistic) transformation. MON802 was further engineered to express resistance to glyphosate, the active ingredient in the herbicide Roundup®, allowing for its use as a weed control option. In order to obtain field tolerance to glyphosate herbicide, two novel genes, CP4 EPSPS and goxv247, were introduced maize by particle acceleration (biolistic) transformation.

The cry1Ab gene produces the insect control protein Cry1Ab, a delta-endotoxin. The Cry1Ab protein produced by the Bt maize is identical to that found in nature and in commercial Bt spray formulations. Cry proteins, of which Cry1Ab 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. Cry1Ab is lethal only when eaten by the larvae of lepidopteran insects (moths and butterflies), 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.

In plants, the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (abbreviated EPSPS) plays a key role in the biochemical pathway that results in the synthesis of the aromatic amino acids phenylalanine, tyrosine, and tryptophan. This enzyme is only present in plants and microorganisms, such as bacteria and fungi, and is not present in animals and humans. In the early 1970s, it was discovered that the simple amino acid analogue, glyphosate, could selectively inhibit the activity of the EPSPS enzyme, thus shutting off aromatic amino acid synthesis. Because these amino acids are needed for protein synthesis, which is required for plant growth and maintenance, the application of glyphosate quickly results in plant death. EPSPS is not present in mammals, birds or aquatic life forms, which do not synthesize their own aromatic amino acids. For this reason, glyphosate has little toxicity to these organisms.

A gene encoding a glyphosate-tolerant form of the EPSPS enzyme was isolated from the CP4 strain of Agrobacterium tumefaciens, a common soil bacterium, and introduced into the maize genome using micro-particle bombardment. MON802 contains a third gene that codes for a modified version of the enzyme glyphosate oxidase (GOX), which accelerates the normal breakdown of glyphosate into two non-toxic products, aminomethylphosphonic acid (AMPA) and glyoxylate. AMPA is the principal breakdown product of glyphosate and is degraded by several microorganisms, while glyoxylate is commonly found in plant cells and is broken down by the glyoxylic pathway for lipid metabolism. The GOX encoding gene (goxv247 was isolated from the bacterium Ochrobactrum anthropi strain LBAA.

MON802 expressed the Cry1Ab protein at an effective dosage over the growing season, as indicated by its efficacy in controlling both first and second-generation infestations of ECB. Protein expression was found to decrease over the growing season, as evidenced by declining Cry1Ab protein concentrations in assayed leaves. MON802 maize has been field tested since 1993 in the major maize growing regions of the United States and Puerto Rico, as well as in Canada (1995, 1996), Chile, Argentina, France, Italy, South Africa, and Costa Rica. The studies demonstrated that MON802 maize retained the agronomic characteristics of the parental line. The transgenic line provided significant protection from feeding damage from ECB throughout the season, while some protection was noted from Southwestern corn borer (Diatraea grandiosella) and corn earworm (Heliothis zea). No significant differences were observed in resistance to a number of other significant insect pests or diseases compared to non-transgenic controls. It was demonstrated that the transformed maize line did not exhibit weedy characteristics, or negatively affect beneficial or nontarget organisms. MON802 was not expected to impact on threatened or endangered species.

Maize does not have any closely related species growing in the wild in the continental United States and Canada. Cultivated maize can naturally cross with annual teosinte (Zea mays ssp. mexicana) when grown in close proximity, however, these wild maize relatives are native to Central America and are not naturalized in North America. Additionally, reproductive and growth characteristics were unchanged in MON802. Gene exchange between MON802 and maize relatives was determined to be negligible in managed ecosystems, with no potential for transfer to wild species in Canada and the United States.

Regulatory authorities in Canada and the United States have mandatory requirements for developers of Bt maize to implement specific Insect Resistant Management (IRM) Programs. The potential for ECB populations to develop tolerance or become resistant to the Bt toxin is expected to increase as more maize acreage is planted with Bt hybrids. These IRM programs are designed to reduce the potential development of Bt-resistant insect populations, as well as prolonging the effectiveness of plant-expressed Bt toxins, and the microbial Bt spray formulations of these same toxins.

The food and livestock feed safety of MON802 maize was established based on several standard criteria. Analyses determined that MON802 grain was nutritionally equivalent to non-transgenic grain, posing no health risks to either humans or livestock. Proximate analysis (ash, crude fat, crude protein, and moisture content), and fatty acid and amino acid composition of MON802 grain revealed only minor differences from the levels reported for non-transgenic maize. These differences were within the normal range of variation for maize and were not linked to the presence of the introduced genes.

The toxicity and allergenicity potential of the Cry1Ab, CP4 EPSPS and GOX proteins expressed in MON802 was assessed by examining their physiochemical characteristics, degree of amino acid sequence homology to known protein allergens, and digestibility. An acute oral gavage feeding study was conducted in which mice were fed high doses of each of the three novel proteins, and did not exhibit any toxic effects. The Cry1Ab protein has a history of safe use, demonstrated by its use in microbial Bt spray formulations in agriculture for more than 40 years with no evidence of adverse effects. No significant amino acid sequence homologies were observed between the Cry1Ab, CP4 EPSPS or GOX proteins and known allergens and toxins. Neither Cry1Ab, CP4 EPSPS, nor GOX possess the characteristics of stability to digestion, heat stability, and glycosylation commonly associated with allergenic proteins.

Links to Further Information Expand

Canadian Food Inspection Agency, Plant Biotechnology Office Impact of Bt corn pollen on monarch butterfly populations: A risk assessment Office of Food Biotechnology, Health Canada U.S.Department of Agriculture, Animal and Plant Health Inspection Service US Food and Drug Administration USDA-APHIS Environmental Assessment

This record was last modified on Monday, March 28, 2016