Petition 07-253-01p: Syngenta'sInsect-ResistantMIR162 Corn Response to Comments

The Animal and Plant Health Inspection Service (APHIS) ofthe United States Department ofAgriculture (USDA) reviewed a Syngentapetition (APHIS No. 07-253­ 01p) requesting a determination ofnonregulated status for their genetically engineered (GE) insect-resistant com cultivar MIR162. Syngenta submitted data supporting their petition that MIR162 com should no longerbe considered a regulated article under APHIS Biotechnology Regulations (7 Code ofFederal Regulations (CFR) part 340) because MIR162 com is unlikely to pose a plantpestrisk. Prior to reaching a determination, APHIS prepared a plantpestrisk assessment (PPRA) to evaluate whether MIR162 com is likely to pose a plant pest risk. Based on the plantpestrisk assessment, APHIS concluded that MIR162 com is unlikely to pose a plantpestrisk and is therefore eligible for nonregulated status. APHIS also prepared a draft environmental assessment (EA) to evaluate whether there couldbe significant impacts on the environment arising from a decision to grant a determination ofnonregulated status to MIR162 com. APHIS prepared the EA as part ofits obligation to meet the statutory requirements ofthe National Environmental Policy Act (NEPA) of 1969 (42 U.S.c.A. § 4321 

### etseq.). As part ofthis process, APHIS consideredpublic comments received on thepetition for a determination ofnonregulated status andassociated draft EA. This document provides APHIS' response to these comments.

On January 13,2010, APHIS published a notice in the Federal Register (75 FR 1749­ 1751, DocketNo. APHIS-2009-0072) announcing the availability ofthe Syngenta petition and the APHIS PPRA and EA for a 60-day public review and commentperiod. This commentperiod ended on March 15,2010. APHIS received a total of35 comments from various groups and individuals. Nineteen comments supported deregulation, while 16 comments generally opposed the development and use ofgenetically engineered foods.

Those supporting a determination ofnonregulated status included six academicians, six individuals from the com industry, four com trade groups, and three com growers. Those opposing a determination ofnonregulated status included a com grower, two Non Governmental Organizations (NGOs) (supplied four comments), and 11 individual

consumers. Supporters ofa determination ofnonregulated status for MIR162 cited a number of benefits they personally observed from growing either MIR162 comtestplots or other insect-resistant Btcom, orbecause oftheir experience dealing with the GE insectresistant com. A few salient observations thatprovide supporting evidence for MIR162

com are: (1) Itwas found effective against a broad spectrum ofdifficult to control lepidopteran pests such as com earworm, fall armyworm, western bean cutworm, black cutworm, and sugarcane borer; (2) Itwould be a useful tool in a lepidopteran insect control strategy within com Integrated Pest Management (IPM) programs; (3) Itreduced foliar chemical sprayby controlling a broad spectrum oflepidopteranpests; (4) It potentially delays lepidopteran insect resistancebecause ithas a different mode ofactionthan other Bt com; (5) Itreduced aflatoxin contamination ofcom grain; (6) Ithas a potential to provide greater economicbenefits to com growers through reduced lepidopteran pest damaged grain loss and/or reduced foliar insect spray; and (7) Any such reduction in use ofchemical insecticides potentially enhances environmental benefits.

A majority ofthose opposed to a determination ofnonregulated status didnot mention their specific disagreement with APHIS' analyses detailed in the EA (USDA-APHIS 2010) orthe PPRA (USDA-APHIS 2009); ratherthey expressed theirgeneral opposition to genetically modified crops. One com grower commented that, contrary to his expectation, the use ofpesticides increased onhis farm when he used GM seeds. Likewise, two individuals expressed theirbeliefthat GE com pollen endangers all honeybees and other insects inthe com agroecosystem. Two individuals expressed their

concern about genetic contamination ofconventional com from GE com and food and feed safety ofGE com. One person specifically mentioned that there is plenty of scientific evidence that GMOs (=GE) are the root cause ofmany diseases. People who expressed their opposition to deregulation didnotprovide any supporting evidence for their claims. In the following paragraphs APHIS reiterates its findings to address the four major concerns expressedbyindividuals.

1. Pesticide use on Insect Resistant GE Corn Crop

A com grower who opposed granting nonregulated status to MIR162 com contends that introduction ofGE crop varieties has led to increased pesticide use rather than decrease

as the providers ofGM seed would lead one to believe. Because ofthis disparity in pesticide usage claim on GM corn, the commenterbelieves that APHIS should not grant nonregulated status to MIR162 comuntil sufficient data are generated to show that plant incorporated protectants, such as Cry and Vip proteins, act as true pesticides.

APHIS disagrees with the commenter's assertion. As summarized in the EA (B7­ Agricultural Benefits, p. 28), adoption ofGE crops is associated with reduced pesticide

use. Insecticide use on fields planted to Bt corn has decreased substantially since introduction ofBtcorn in the mid 1 990s (Figure 1 in EA; also see figure 8 in FernandezCornejo and Caswell 2006) and use rates (in terms ofactive ingredient) on corn has declined since the introduction ofGE corn in 1996. Using 2001 data, USDA-ERS found that insecticide use was 8 percent lower per planted acre for adopters ofBtcorn than for nonadopters (Fernandez-Cornejo and Li 2005). The USDA-ERS results generally agree with field-test and other farm surveys that have examined the effects ofusing GE crops (Table 1 in EA). The MIR162 corn and stacked hybrids may further reduce insecticide

use ifthe currenttrend in insecticide usage continues (Figure 8 in Fernandez-Cornejo and Caswell 2006).

As discussed in the EA (III. Introduction, p. 7) and petition (LB. Rationale for Development ofMIR162 Maize, pp. 11-13), currently available insect-resistant Bt crops
are highly effective against European corn borer (Ostrinia nubilalis) and southern and western com rootworm species (Diabrotica spp). But com is susceptible to attackby a variety ofinsects (Table 1, pg. 12 in petition) from the time it is planted until it is

2consumed as food or feed. Current Bt comcultivars provideonly limited protection against feeding damage caused by com earworm 

### (Helicoverpa zea), fall armyworm 

### (Spodopterafrugiperda), black cutworm 

### (Agrotis ipsilon), andwestern bean cutworm 

### (Striacosta albicosta). Syngenta developed MIR162 to provide resistance to those latter

cominsectpests. Moreover, when MIR162 comtraits are combined with previously deregulated Bttraits in one ormore cultivars, such cultivars would be expected to provide a wide range ofprotection against a variety ofinsectpests, further reducing insecticide use in the future (Fernandez-Cornejo and Caswell 2006).



### 2. Impact ofMIR162 Corn on Honeybees and Other Beneficial Insects

An NGO commentedthatpesticides harm honeybees, therefore, GE pesticides similar to the onepresent in MIR162 com are goingto endangerhoneybee populations ifsuch com varieties are grantednonregulated status.

APHIS' analyses on impact ofthe introduced geneproduct in MIR162 com are presented in the EA (B-5. Potential Impact onNon-target Organisms, Including Beneficial Organisms andThreatened orEndangered Species, pp. 22-25) and data are provided in the petition (VII.C.3. Expected Environmental Concentrations for Nontarget Organisms, pp. 78-83; Impact onNontarget Organisms, pp. 84-89; for honey bee dataplease see the sections VII.C.3.c. EEC for Pollinators, p. 80 andVII.D.3. Effect ofVip3Aa on Pollinators).

TheVip3Aa20 protein is selectively toxic to a few species ofinsectpests belonging to the orderLepidoptera. Non-Lepidopteran insect species are not expected to be affected bytheVip3Aa20 protein. Its receptor-mediated mechanism ofaction and the absence of activity in bioassays with multiple species outside ofthe orderLepidoptera supportthis conclusion. Furthermore, Syngenta observed no harmful effects ofVip3Aaproteins on representative non-target organisms that are associated with com agroecosystems orin their hazard identification studies that used a wide range oftaxa at expected environmental concentrations (Table 31, pg. 89 ofpetition). In thehoneybee 

### (Apis mellifera) study conductedby Syngenta, there were no observable adverse effects or differences in survival noted at doses ofVip3Aproteins that were well above those expected from exposure to the Vip3Aa20 protein from MIR162 complanted in the field (petition Table 30, p. 84 and Table 31, pg. 89). According to the Environmental Protection Agency's Biopesticides Registration Document on Vip3Aa20 Maize (EPA 2009) there are enough empirical data from peer-reviewed publications providing support that Bt crops have not caused any adverse effects on nontarget organisms, including honeybees.



### 3. Genetically Engineered Corn Contaminates Conventional Corn Cultivars through Gene Flow

Two NGOs oppose granting nonregulated status to MIR162 com because gene flow from GE com varieties is going to contaminate conventional com cultivars threatening their survival.

3Available data on com gene flow and APHIS' assessment ofthe petition data do not supportthis assertion. Gene flow is a natural biological process with significant evolutionary importance. A number offlowering plants are the product ofgene flow and introgression (Grant 1981; Soltis and Soltis 1993; Rieseberg 1997), and even in the existing floras, the occurrence ofhybridization or introgression is reportedto be widespread (Knobloch 1972; Stace 1987; Rieseberg and Wendel 1993; Peterson et al. 2002). Gene flow between crop cultivars is also very common (Ellstrand et aI. 1999; Stewart et al. 2003). ). Ithas been a common practice byplantbreeders to artificially introgress traits from wild relatives into crop plants to develop new cultivars. Traditional com, landrace com, orelite non-GE com are all ultimately derived from their ancestral parental species teosinte through human selection (White and Doebley 1998; Doebley 2004). Furthermore, a few important genes, such as dwarfing genes in wheat and rice, (Hedden 2003) and the teosinte branching gene in com (Doebley etaI. 1995), have transformed agriculture across the globe. Thus, the end product ofgenetic engineering techniques is not different from what has been practiced through conventional breeding techniques. Also, the food, feed and environmental safety ofthe introduced genes, obtained eithervia conventional breeding orGE, solely depends on the nature ofthe gene products. A body ofscientific evidence shows that gene flow per se does not contaminate plantpopulations, rather it can increase ordecrease genetic diversity ofplantpopulations.

APHIS recognizes that comis open-pollinating and itis possible that the engineered genes could move viawind-blown pollen to an adjacent field. All com, whether genetically engineered ornot, can transferpollen to nearby cornfields. However, an influx ofpollen originating from a given com varietymay not appreciably change the characteristics ofcom in adjacent fields because gene flow declines rapidly with increased distances from a pollen source popUlation (Halsey et aI. 2005). Otherfactors such as wind speed, host variety and temperature also affect pollen flow (Aylor et aI., 2003; Jones and Brooks, 1950). For example, in a study assessing observations ofa large number ofcommercial canola fields, the incidence ofgene flow was on the order of 0.015 % at 500m (see Fig 2 in Rieger, 2002). In a smaller comresearch study, the incidence ofgene flow was 0.05% at 100m (Goggia et aI., 2006). Methods ofspatial and temporal isolation are widely used and accepted when seed producers are seeking to minimize the influx ofpollen from sources outside a seed production field. These methods are readily applicable to the production ofcertified organic com seed. To maintain varietal purity, AOSCA (Association ofOfficial Seed Certifying Agencies) recommends 200 meters isolation from nearby compopUlations to produce the foundation class ofcertified seed (AOSCA 2003).

There aremanypractices non-GE comproducers use to preventmovement ofGE com or the pollen from GE cominto theirproduction fields (Bradford 2006; Schienmann 2003; Ziegler2000). Growers may chose to plant earlier orlaterthan neighboring farmers who may be using GE crops, ensuring thatthe flowering times between GE and non-GE produced crops will differ, thus minimizing the chance ofpollen movement between fields. They may also employ adequate isolation distances between different com crops field to minimize the chance that pollen will be carried between the fields.



### 4When Syngentareceives regulatory approval from APHIS, it will likely make MIR162

corn available to growers and breeders. Itis notlikely that buyers and sellers who choose notto plant or sell MIR162 corn orothertransgenic cornvarieties will be significantly impactedbythe expected commercial use ofthis productbecause: (a) nontransgenic corn varieties will likely still be sold and will be readily available to those who wish to plantthem; (b) Syngenta's stewardshipplan will provide farmers that purchase MIR162 corn with recommended managementpractices for MIR162 corn cultivation; (c) methods ofspatial and temporal isolation are widelyused and accepted and corn seed producers employing them can minimize the influx ofpollen from sources outside the seedproduction field; (d) 85% ofthe 2008 corn acreage in the United States is already plantedto transgenic herbicide tolerant and/or insectresistant varieties; and (e) APHIS expects thatMIR162 may replace some ofthe presently available GE corn varieties without significantly affecting the overall total corn acreage. APHIS concludes that farmers who cultivatenon-GE corn crops will be able to coexistwith GE cornproducers

as they do now.


### 4. Food and Feed Safety ofMIR162 Corn for Humans and Animals Two NGOs expressed concerns that the long-term consequences ofGE food are not fully understood andthere is plenty ofscientific evidence that GE food is theroot cause of many diseases.

APHIS disagrees with commenter's' statements. As summarized in the EA (Human and Environmental Benefits, p. 32) there were no human health concerns observed with respect to toxicity or allergenicity oftheproteins expressed in MIR162 corn. In a variety offield studies, otherinsectprotected corn expressing Btproteins havebeen shown to have significantly lower levels ofcommon mycotoxins that are produced by fungal pathogens (Wu 2006).

A comprehensive safety assessment ofthe Vip3Aa20 and PMI (Phosphomannose isomerase) proteins demonstrated that bothproteins are nontoxic to mammalian species and are unlikely to be food allergens (69 FR26770-26775; 73 FR45620-45624; FDA BNFNo. 000113). The Vip3Aa20protein is considered nontoxic because it does not share significant amino acid homology with knownprotein toxins, is non-toxic to mice at
a very high dose, is rapidly degraded in simulated mammalian gastric fluid, and its insecticidal mode ofaction for Vip3Aa20 is notrelevant to mammals.
Vip3Aa20 is also not likely to be a food allergenbecause it is not derived from a known

source ofallergenic proteins, it does not have significant amino acid sequence identity to known allergenic proteins, it is rapidly degraded in simulatedmammalian gastric fluid, and it is labile upon heating attemperatures of65°C and above. On August 6, 2008, EPA granted an exemption from the requirement ofa tolerance for residues ofB. thuringiensis Vip3Aaproteins (including the Vip3Aa20 variant) in oron food and feed commodities of

corn (73 FR 45620-45624).

5PMI is considered nontoxic because it does not share significant amino acid homology with known protein toxins, it is nontoxic to mice at a very high dose, and it israpidly degraded in simulated mammalian gastric fluid. PMI is not likely to be a food allergen because it is not derived from a known source ofallergenic proteins, it does not have significant amino acid sequence identity to known allergenic proteins with implications for its allergenic potential, it is rapidly degraded in simulated mammalian gastric fluid, and it is labile upon heating at temperatures of37°C and above. A permanent exemption from the requirement ofa food tolerance currently exists under 73 FR45620-4562440 for Vip3Aa20 in maize and under 40 CFR §180.1252 for PMI in all plants.

As presentedin Appendix II ofthe EA (p. 50), the compositional analyses ofcorn grain revealedno statistically significant differences between MIR162 and control means for 43 ofthe 56 analytes including carbohydrates, proteins, fats, minerals and vitamins. Collectively, even for those few analytes that showed some difference, the observed differences between MIR162 and control means are considered ofno biological significance andrepresent typical random variance. The magnitude ofthe differences

was small (all MIR162 values fell within normal ranges for conventional maize) and the MIR162 and control data ranges significantly overlapped. MIR162 is therefore, not compositionally different from conventional maize.

A food and feed nutritional and safety assessment ofMIR162 corn has been completed bythe FDA. Under Federal Food, Drug, and Cosmetic Act (FFDCA), it is the responsibility offood and feed manufacturers to ensure thatthe products they market are safe andproperly labeled. Food and feed derived from MIR162 corn mustbe in compliance with all applicable legal and regulatory requirements. FDA completedtheir consultation on MIR162 on December 9,2008 and concluded that it had "no further questions concerning grain and forage derived from corn event MIRI62" (FDA BNF No. 000113).
According to the Society ofToxicologyposition paper on the safety ofgenetically modified foods produced through biotechnology (Hollingworth et al. 2003), the available scientific evidence indicates thatthe potential adverse health effects arising from biotechnology-derived foods are not different in nature from those created by conventional breedingpractices for plant, animal, ormicrobial enhancement, and are already familiar to toxicologists. The authors contend that it is therefore important to recognize that the food product itself, rather than the process through which it is made, shouldbe the focus ofattention in assessing safety.

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