GM Crop Database

Database Product Description

COT102 (SYN-IR1Ø2-7)
Host Organism
Gossypium hirsutum (Cotton)
Trait

Insect resistant, Lepidoptera.

Trait Introduction
Agrobacterium tumefaciens-mediated plant transformation.
Proposed Use

Production for fibre, livestock feed, and human consumption.

Product Developer
Syngenta Seeds, Inc.

Summary of Regulatory Approvals

Country Food Feed Environment Notes
Australia 2005
Canada 2011 2011
China 2016 2016
Colombia 2016
Japan 2012 2012
Korea 2014
Mexico 2010 2010
New Zealand 2005
Philippines 2015 2015
Taiwan 2015
United States 2005 2005 2005

Introduction Expand

The cotton line COT102 was developed to resist attack by lepidopteran insects pests such as cotton bollworm (Helicoverpa zea), tobacco budworm (Heliothis virescens), pink bollworm (Pectinophora gossypiella), fall armyworm (Spodoptera frugiperda), beet armyworm (Spodoptera exigua), soybean looper (Pseudoplusia includens), cabbage looper (Trichoplusia ni), and cotton leaf perforator (Bucculatrix thurberiella). The vegetative insecticidal protein VIP3A, which is a product of a gene originally derived from Bacillus thuringiensis strain AB88, is produced in the tissues of COT102. The VIP3A proteins act by binding to specific sites located in the midgut epithelium of susceptible insect species of the order Lepidoptera. Following binding, cation-specific pores are formed that disrupt ion flow in the midgut, thereby causing paralysis and death. The insecticidal nature of the VIP3A protein is attributable to the presence of specific binding sites in these insects, which are different than those specific to Cry1Ab and Cry1Ac. There are no binding sites in the epithelium of mammalian and avian intestinal sites for the vegetative insecticidal proteins of B. thuringiensis. Humans and livestock animals are therefore not susceptible to the damaging effects of these proteins.

Summary of Introduced Genetic Elements Expand

Code Name Type Promoter, other Terminator Copies Form
vip3A(a) VIP3A vegetative insecticidal protein IR modified promoter, first exon and intron of Arabidopsis thaliana actin-2 gene A. tumefaciens nopaline synthase (nos) 3'-untranslated region 1 functional modified for plant-preferred codons
aph4 hygromycin-B phosphotransferase SM promoter and first intron of A. thaliana ubiquitin-3 gene A. tumefaciens nopaline synthase (nos) 3'-untranslated region 1 functional

Characteristics of Gossypium hirsutum (Cotton) Expand

Center of Origin Reproduction Toxins Allergenicity

Believed to originate in Meso-America (Peruvian-Ecuadorian-Bolivian region).

Generally self-pollinating, but can be cross-pollinating in the presence of suitable insect pollinators (bees). In the U.S., compatible species include G. hirsutum, G. barbadense, and G. tomentosum.

Gossypol in cottonseed meal.

Cotton is not considered to be allergenic, although there are rare, anecdotal reports of allergic reactions in the literature.

Donor Organism Characteristics Expand

Latin Name Gene Pathogenicity
Bacillus thuringiensis strain AB88 5AT

While target lepidopteran insects are susceptible to oral doses of VIP proteins, there is no evidence of toxic effects in laboratory mammals, in birds, and in non-target arthropods, including beneficial insects.

Modification Method Expand

Event COT102 cotton was produced by Agrobacterium-mediated transformation of the cotton variety ‘Coker 312.’ Transformation was achieved using the vector pCOT1, which contained sequences corresponding to a synthetic vip3A(a) gene from Bacillus thuringiensis strain AB88 coding for the vegetative insecticidal protein VIP3A, and the aph4 gene from E. coli, coding for hygromycin-B phosphotransferase (APH4), an enzyme which confers resistance to the antibiotic hygromycin. Transcription of the vip3A(a) gene was directed by modified promoter sequences of the actin-2 gene from Arabidopsis thaliana, including the first exon and intron from the non-translated leader sequence. Terminator and polyadenylation sequences were derived from the 3' nontranslated terminator sequences of the nopaline synthase (nos) gene from Agrobacterium tumefaciens. The expression of the aph4 gene was regulated by promoter sequences, as well as the first intron of the ubiquitin-3 gene from A. thaliana. Terminator and polyadelination sequences for the aph4 gene were identical to those used for the vip3A(a) gene. Vector backbone sequences included the streptomycin adenyltransferase (aadA) gene, which confers resistance to streptomycin and spectinomycin, and was used as a bacterial selectable marker.

The expression of the aph4 gene in successfully transformed cells allowed their selection on culture medium containing hygromycin. Successful transformants were regenerated and tested for resistance to lepidopteran pests. The successful event was designated COT102, was selfed to produce seed, and subsequently backcrossed into commercial cotton germplasm.

Characteristics of the Modification Expand

The Introduced DNA

Southern blot analysis of the genomic DNA from COT102 revealed the incorporation of single intact copies of the vip3A(a) and aph4 genes, along with intact copies of their respective regulatory sequences. Results of these analyses also demonstrated that none of the vector backbone sequences, including the streptomycin adenyltransferase (aadA) gene, were incorporated into the genomic DNA.

The synthetic vip3A(a) gene in COT102 encodes a 789-amino acid polypeptide virtually identical to the protein encoded by the gene from B. thruringiensis strain AB88. The vip3A(a) gene was synthesized to optimize its expression in plants and encodes for glutamine at position 284 instead of lysine. The biochemical properties of the modified VIP3A are identical to that of the bacterial protein. Studies conducted with trypsin and lepidopteran gut proteases demonstrated that the 60 kDa toxic core is cleaved from the full-length 89 kDa VIP3A protein, similar to the native bacterial protein.

Genetic Stability of the Trait

The stability of the inserted insect resistance trait in COT102 was assessed over five generations using Southern blot analysis and segregation analysis. Statistical analysis of the segregation data demonstrated the stability of the trait over the five generations, and a Mendelian inheritance typical of a single dominant trait.

Expressed Material

The levels of VIP3A and APH4 proteins in COT102 were quantified using enzyme-linked immunosorbant assay (ELISA) methods. Cotton tissue was sampled at six growth stages, from field trials at 3 locations in 2002. Mean whole plant levels of VIP3A declined with advancing growth stage: 12.11µg/g at the 4-leaf stage, 5 - 5.28 µg/g at first bloom and first open boll respectively, and 1.75 µu/g at pre-harvest. VIP3A concentrations were the highest in leaves, averaging 15.31 µg/g at 4-leaf stage, 17.55 µg/g at squaring, 9.73 µg/g at first bloom, 5.29 µg/g at peak bloom, 8.82 µg/g at first open boll, and 4.73 µg/g at pre-harvest. A maximum of 136 µg/g was detected in leaves at squaring. Levels of VIP3A were the lowest in roots (1.39 µg/g at the 4-leaf stage, 1.5 µg/g at peak bloom, and 1.18 µg/g at pre-harvest), as well as in bolls (1.0 µg/g at peak bloom, and below the level of quantification [The APH4 protein was not consistently detected leaves, squares, roots, bolls, seeds and nectar, and when detected, was below the lower limit of quantification for this protein (150 ng/g dry weight). However, the protein was quantified in pollen at 2.3 µg/g.

Environmental Safety Considerations Expand

Field Testing

Event COT102 was field tested at several locations in the United States, from 2000 to 2002, to evaluate agronomic performance, disease and insect resistance, and efficacy of the lepidopteran resistance trait in COT102 compared to its non-modified parental line Coker 312. Parameters measured included plant growth, morphology, reproductive traits, fibre yield and quality. At some of the locations, boll yield was significantly greater, and fibre quality significantly superior in COT102 compared to Coker 312. This was attributed to greater insect pressure at these locations; greater insect damage in Coker 312 compared to COT102 resulted in delayed maturity of the bolls, hence lower yield and decreased fibre quality. However, field trial results generally indicated that plant growth and morphology, agronomic performance and disease and non-lepidopteran susceptibility of COT102 was similar to that of its parental line. Differences that were observed were not consistent among locations, or among years, and were within the range of variability for conventional cotton cultivars. Since there were no biologically meaningful differences in disease and non-lepidopteran insect susceptibilities, and in vegetative and reproductive growth, COT102 is not expected to become a plant pest risk, neither in terms of weediness, nor in increased suspectibility to plant diseases and insects other than Lepidoptera.

Outcrossing

Cotton (G. hirsutum) is mainly a self-pollinating plant, but pollen is also routinely transferred by insects, particularly bumblebees and honey bees. The pollen is heavy and sticky and the range of natural crossing is limited. Outcrossing rates of up to 28% to other cotton cultivars grown directly adjacent to the pollen source have been observed under field conditions when sufficient insect pollinators have been present. The rate of outcrossing declines rapidly with increased distance from the pollen source. Results of outcrossing research trials in the United States have shown that pollen movement decreases rapidly at 12 metres from the pollen source. Nevertheless, certified seed cotton growers in the United States must maintain an isolation distance of 202 metres between fields. If COT102 were to be grown in proximity with other cotton cultivars, and sufficient insect pollinators were present and active, the vip3A(a) gene could possibly introgress into these cultivars. In the event of the formation of hybrids, there would no competitive advantage conferred on any hybrid progeny in the absence of infestations by Lepidopteran insect species.

In the United States, species genetically compatible with COT102 cotton include G. hirsutum (wild or under cultivation), G. barbadense (cultivated Pima cotton), and G. tomentosum. Outcrossing from G. hirsutum to G. barbadense is possible under suitable conditions, such as the presence of pollinators. G. thurberi is another wild species found in the United States, but it is genetically incompatible with G. hirsutum. While G. hirsutum and G. tomentosum are genetically compatible (both possess the AADD genome), the possibility of gene transfer is unlikely due to the non-synchronous flowering periods (day for G. hirsutum and night for G. tomentosum), and lack of common pollinators. Populations of wild Gossypium species occur in southern Florida (G. hirsutum), Hawaii (G. tomentosum), Puerto Rico and the U.S. Virgin Islands. In other cotton growing areas of the world, species that could intercross with G. hirsutum include G. mustelinum in Brazil, and G. lanceolatum in Mexico.

Weediness Potential

Cultivated Gossypium hirsutum is not typically considered a weed species in the United States or other countries, but it is listed as a potential weed in southern Florida. Although cotton is cultivated as an annual crop, it behaves as a perennial in undisturbed environments and suitable climatic conditions. Cotton does not tolerate cold conditions thereby limiting its overwintering potential to southern Florida, Hawaii, and Puerto Rico.

No competitive advantage was conferred to COT102 other than the production of the insecticidal protein VIP3A, and it is not expected to become weedy or invasive of natural habitats since none of the reproductive or vegetative growth characteristics of this line were substantially modified. Differences in these characteristics that were observed were not consistent among locations, and were therefore due to environment, including variability in insect pressure among locations. Seed dormancy, germination, and seedling establishment, were not significantly altered in COT102, compared to the parental line Coker 312, and observed differences were within the range of variability for conventional cotton cultivars.

Secondary and Non-Target Adverse Effects

Event COT102 cotton was developed to resist lepidopteran pests of cotton. Due to the insecticidal nature of the VIP3A protein, the impact of COT102 on non-target organisms, including non-target insect pests, was investigated. Ecological toxicity studies were conducted with representative terrestrial and aquatic species that could be inadvertently affected by the insecticidal protein VIP3A. Non-target organisms included insects other than lepidopterans (honeybees, ladybird beetles, and green lacewings), soil arthropods (Collembola, earthworms), and representative terrestrial and aquatic species such as mice, bobwhite quail, catfish and Daphnia magna.

Toxicological effects of were determined from acute feeding studies. Leaf tissue and cottonseed from COT102 were not used in these studies to avoid possible confounding effects of the natural toxicants of cotton (e.g., gossypol). The organisms were fed VIP3A protein derived from either recombinant E. coli, or maize expressing the vip3A(a) gene. The VIP3A protein from both these sources was shown to be equivalent to that expressed by COT102 cotton, as demonstrated by similarity in molecular weight, immunoreactivity, results of mass spectral analysis of the peptides, and similarity in the rank-order of bioactivity against four species of VIP3A-sensitive lepidopteran larvae.

Most of the organisms in the acute feeding studies were fed, at the highest treatments, levels of VIP3A that were several times greater than the estimated environmental concentrations, based on the expression levels in COT102 tissues. No adverse effects were observed in any of the tested organisms at the highest treatment levels. For each of these organisms, the highest treatment levels represented the following exposure to VIP3A from COT102: Bobwhite quail, 21-fold the level in leaves, and >1200-fold the level in cottonseed; honeybee larvae, >77-fold the level in pollen; adult honeybees, >8-fold the level in pollen; ladybird beetles and lacewings, > 133-fold the level in pollen; Collembola and earthworm, >2100- and 180-fold the estimated soil concentration, respectively.

Environmental concentrations of VIP3A from COT102 were not estimated for either Daphnia magma or catfish. Aquatic organisms would most likely be exposed to VIP3A protein from COT102 pollen drifting from nearby fields and depositing on the surface of the water. This represents a very minimal amount of exposure since cotton flowers are mostly self-pollinating, and the pollen is heavy, thereby minimizing dispersal by wind. No adverse effects were observed in either Daphnia magna or catfish when fed at the highest levels of the VIP3A protein.

The effect of VIP3A on mammals was investigated in an acute feeding study conducted with mice. VIP3A expressed in maize tissue was fed, by gavage, at 5000 mg/kg of body weight. VIP3A expressed in E. coli was also fed at 5050 mg/kg of body weight. No adverse effects were observed in the mice, fed either diet, during the 14 days of the acute feeding study. The digestibility of VIP3A in simulated gastric fluids was also investigated. The VIP3A protein expressed in E. coli was degraded, at time zero, to low molecular weight (< 14,000) peptides, and no peptides were detectable after 2 min. The VIP3A protein is therefore rapidly digested in a mammalian gut environment.

VIP3A protein in COT102 cotton was shown to be insecticidal toward several lepidopteran pests of cotton, including cotton bollworm, tobacco budworm, pink bollworm, fall armyworm, beet armyworm, soybean looper, and cabbage looper. However, several lepidopteran pest species were not adversely affected by the protein, including the European Corn Borer (Ostrinia nubilalis), Fall webworm (Hyphantria curea) and Diamondback moth (Plutella zylostella).

The potential for exposure of non-target lepidopterans to the VIP3A protein was investigated. Insect sensitivity studies were conducted on the Monarch butterfly (Danaus plexippus) and demonstrated no adverse effects. The most likely route of exposure to non-target lepidopterans would be through the pollen. Cotton flowers are mostly self-pollinated and therefore very little pollen would be dispersed into the environment. Cotton pollen is also not readily dispersed by wind due to its mass and high moisture content. The exposure to VIP3A via cotton pollen would also be minimal due to the low levels of expression in the pollen.

Based on the results of the ecotoxicological studies, the VIP3A protein in COT102 poses a negligible risk to non-target organisms, including beneficial arthropod species. The cultivation of COT102 therefore poses no greater risk to interacting, non-target organisms, than conventional cotton cultivars.

Impact on Biodiversity

Event COT102 did not exhibit novel phenotypic characteristics that would increase its survival in either unmanaged habitats, or in areas outside of the current geographical range of cotton production. Since the potential of gene transfer to wild relatives in the United States is quite minimal, the risk of transferring the insect resistance trait to species in unmanaged habitats is insignificant. In countries (e.g., Brazil, Mexico) where hybrids could form with wild relatives of cotton, the introgression of the insect resistance trait into these wild species would confer no other advantage than increased resistance to attack by certain Lepidopteran insects.

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 the United States have required developers to implement specific Insect Resistant Management (IRM) Programs. These programs are mandatory for all transgenic Bt-expressing plants, including COT102 cotton, 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.

Food and/or Feed Safety Considerations Expand

Dietary Exposure

The genetic modification of COT102 cotton would not be expected to result in any change in the consumption pattern of cotton products. The seed and oil fractions from this cotton line did not exhibit any novel characteristics that would alter the consumption pattern. This was confirmed by comparison of the levels of proximates and fatty acids in COT102 compared to the parental line. Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. Processed linters are composed of pure (>99%) cellulose and are treated with heat and solvent; these processes would be expected to remove and destroy any residual protein.

Nutritional and Compositional Data

The nutritional and anti-nutritional components of COT102 cottonseed were determined analytically and compared to cottonseed from the non-transgenic counterpart Coker312. Samples for analysis were obtained from field trials conducted at three locations in 2001, and two locations in 2002. Samples were obtained from each replicate of each trial in 2002, whereas only single samples were obtained from each location in 2001. The following components were determined: proximates (moisture, fat, crude protein, crude fibre, total dietary fibre, ash, carbohydrates, acid detergent fibre, and neutral detergent fibre); minerals (phosphorus, calcium, sodium, iron, magnesium, manganese, potassium, zinc, copper and chromium); fatty acids (myristic, palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, arachidic, and behenic); amino acids (aspartate, threonine, serine, glutamate, praline, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, lysine, arginine, and tryptophan), and natural toxicants (total gossypol, free gossypol, and the cyclopropenoid fatty acids: sterculic, malvalic and dihydrosterculic). Levels of total and free gossypol were also determined in oil, non-toasted meal, and toasted meal obtained from a 2001 cottonseed sample.

Data from analyses of the 2001 samples demonstrated that, other than differences in the levels of the amino acids lysine and tyrosine, which were significantly higher in COT102, there were no statistically significant differences in the composition of COT102 compared to its non-transgenic parental line Coker 312. Analyses of the 2002 samples revealed significantly lower levels of iron, zinc, copper, as well as serine and lysine in COT102. However, none of the observed differences in nutritional composition, in both the 2001 and 2002 samples, were found to be biologically significant. No statistically significant differences were observed in the levels of gossypol (total and free) and cyclopropenoid fatty acids, in the seed, oil and meal. The levels of nutrients and anti-nutrients in both COT102 and Coker 312 were also compared to those in the published literature. Other than the levels of some of the amino acids from the 2001 samples, in both COT102 and Coker 312, the levels of all other components fell within the observed ranges for conventional, non-transgenic cotton cultivars. Based on these results, it was concluded that COT102 is equivalent to non-transgenic cotton, and that the genetic modification did not alter the nutritional and anti-nutritional composition.

Toxicity and Allergenicity

The potential for toxicity and allergenicity of the novel proteins VIP3A and APH4 was determined from results of acute feeding studies using mice, from in-vitro digestibility studies using simulated mammalian gastric fluids, and from the expression levels in COT102 tissues. No adverse effects were observed in the acute studies, in which mice were fed the VIP3A protein at levels far exceeding the estimated environmental exposure, based on the expression levels in tissues. The intestinal epithelial tissues of VIP3A-fed mice were studied, microscopically and immunologically, and no changes were observed, compared to mice fed a diet without VIP3A protein. No observed effects were observed in mice exposed to a very high oral dose of the APH4 protein; the exposure level to non-target organisms is also very low due to levels of APH4 in most tissues that were below quantifiable levels of detection. The VIP3A protein was completely hydrolyzed in simulated mammalian gut fluids, which further demonstrated the lack of toxicity and allergenicity of the protein. The results of these studies led to the conclusion that the novel proteins VIP3A and APH4 in event COT102 cotton are neither toxic or allergenic to non-target organisms, including mammalian species.

Abstract Collapse

Cotton (Gossypium hirsutum L.) was grown commercially in over 80 countries with a combined production of 44.2 million metric tonnes of cotton seed and 24.8 million metric tonnes of cotton lint in 2006. The major producers of cotton seed and lint were China, the United States, India, Pakistan, Brazil, Uzbekistan and Turkey. Cotton is primarily grown for its seed bolls that produce fibres used in numerous textile products.

About two thirds of the harvested cotton crop is seed, which is separated from the lint during ginning. The cotton seed is crushed to produce cottonseed oil, cottonseed cake (meal), and hulls. Cottonseed oil is used primarily as a cooking oil, in shortening, margarine and salad dressing, and is used extensively in the preparation of snack foods such as crackers, cookies and chips. The meal and hulls are an important protein concentrate for livestock, and may also serve as bedding and fuel. Linters, or fuzz, which are not removed in ginning, are used in felts, upholstery, mattresses, twine, wicks, carpets, surgical cottons, and in industrial products such as rayon, film, shatterproof glass, plastics, sausage skins, lacquers, and cellulose explosives.

Tobacco budworm (Heliothis virescens), pink bollworm (Pectinophora gossypiella), and cotton bollworm (Helicoverpa zea) are three of the most destructive pests of cotton. These insects cause damage to squares and bolls (tobacco budworm, cotton bollworm) and staining of lint (pink bollworm). Species such as the soybean looper (Pseudoplusia includens) and beet armyworm (Spodoptera exigua) cause feeding damage to leaves. Insect damage to the plant also increases susceptibility to diseases (e.g., boll rot), and ultimately results in the losses of yield and crop quality.

Methods of insect control in cotton include the use of insecticides and integrated pest management methods, such as scouting and the use of economic thresholds, prior to application. In 2004, 64% of the cotton acreage in the United States was treated with insecticides; those most commonly used were malathion, acephate and aldicarb. However, the effectiveness of many insecticides has been reduced due to the development of resistance in some insect pests, such as the tobacco budworm.

The cotton line COT102 was genetically engineered to resist attack from lepidopteran insect pests such as the cotton bollworm (Helicoverpa zea), tobacco budworm (Heliothis virescens), pink bollworm (Pectinophora gossypiella), fall armyworm (Spodoptera frugiperda), beet armyworm (Spodoptera exigua), soybean looper (Pseudoplusia includens), and cabbage looper (Trichoplusia ni), and cotton leaf perforator (Bucculatrix thurberiella). This insect resistance is conferred by the vip3A(a) gene, originally isolated from the common soil bacterium Bacillus thuringiensis (Bt) strain AB88. The vip3A(a) gene produces the insect control protein VIP3A in the plant tissues. VIP3A is a member of a class of recently discovered insecticidal proteins: VIP (vegetative insecticidal proteins) proteins are expressed by the bacterium during the vegetative stage, as well as during sporulation, the stage at which the delta-endotoxins (i.e., Cry proteins) are expressed. VIP proteins have an insecticidal mode of action similar to that of the delta-endotoxins: the ingestion by targeted insects leads to feeding cessation, loss of gut peristalsis, insect paralysis, and death. As with Cry proteins, VIP proteins also possess an active proteolytic core, which is activated by insect gut proteases, and binds to specific sites localized on the midgut lining of susceptible insect species. However, the VIP3A protein targets different molecules (i.e., receptors) in the mid-gut lining, and the binding results in the formation of ion channels distinct from those formed by delta endotoxins, such as Cry1Ab. VIP proteins are not expected to affect other invertebrate and vertebrate organisms, including beneficial arthropods, birds and mammals. Only lepidopteran insect species possess VIP binding sites on the surface of their gut epithelia, therefore, livestock animals and humans are not susceptible to these proteins. Also, since only lepidopteran insect species are targeted by the VIP proteins, species of other insect orders, including beneficial and pest species, are not expected to be affected by this insecticidal protein.

COT102 cotton was developed as an alternative and novel insect control option for lepidopteran pests of cotton. COT102 was also developed to help prevent and manage resistance to Cry proteins due to the different insecticidal mode of action of VIP proteins. The vip3A gene was introduced into the cotton line ‘Coker 312’ by Agrobacterium-mediated transformation and the successfully transformed event was termed COT102. Also introduced into COT102 was the aph4 gene, coding for hygromycin-B phosphotransferase (APH4), and used as a selectable marker.

The cotton line COT102 was field tested at several locations in the United States from 2000 to 2002. Characteristics such as yield, boll size, plant growth and morphology, seed germination, flowering and maturity were found to be similar to the parental line ‘Coker 312,’ and also within the range of variability for commercial cotton cultivars. Susceptibility to diseases and non-lepidopteran insects was not altered compared to the parental line. COT102 did not demonstrate morphological, vegetative or reproductive growth characteristics such as those observed in weedy and invasive plant species.

The effect of the cultivation of COT102, specifically that of the insecticidal protein VIP3A, on non-target organisms was investigated during field testing, as well as in ecotoxicological studies. Non-target insects were not detrimentally affected by the insecticidal protein in COT102. VIP3A protein was found to be insecticidal to several lepidopteran species, many of which are pests of cotton; however, VIP3A did not demonstrate insecticidal activity towards lepidopterans such as the European Corn Borer (Ostrinia nubilalis>) and the Monarch butterfly (Danaus plexipus). Non-target organisms, such as arthropods, mammals, birds, and aquatic organisms were not negatively affected by the VIP3A protein in COT102. The cultivation of COT102 would therefore pose no greater risk to interacting, non-target organisms, than conventional cotton cultivars, with the exception of specific lepidopteran insect pests.

The potential for introgression of the insect resistance trait from COT102 cotton into other cotton plants, or to wild relatives of cotton, was investigated. Cotton plants are primarily self-pollinating, but insects, especially bumblebees and honeybees, also distribute cotton pollen. Cotton can cross-pollinate with compatible species including G. hirsutum (wild or under cultivation) and G. barbadense (cultivated Pima cotton), and is genetically compatible with G. tomentosum. Overall, the probability of gene transfer to wild species in unmanaged ecosystems is low due to the relatively isolated distribution of Gossypium species, different breeding systems, and genomic incompatibility. Assuming proximity, synchronicity of flowering and presence of insects, COT012 could freely hybridize with other G. hirsutum varieties and wild plants. In the event of the formation of hybrids, there would no competitive advantage conferred on any hybrid progeny in the absence of infestations by certain Lepidopteran insect species.

The potential for toxicity and allergenicity of the novel proteins VIP3A and APH4 was determined from results of ecotoxicological studies using VIP3A on non-target organisms, from acute feeding studies using mice, from in-vitro digestibility studies using simulated mammalian gastric fluids, and from the expression levels of in COT102 tissues. No adverse effects were observed in the non-target organisms, which were fed the VIP3A protein at levels that far exceeding the estimated environmental exposure, based on the expression levels in tissues. No adverse effects were observed in the acute feeding studies with mice. The intestinal epithelial tissues of VIP3A-fed mice were studied and no changes were observed in these tissues, compared to mice fed a diet without the VIP3A protein. No observed effects were observed in mice exposed to a very high oral dose of the APH4 protein; the exposure level to non-target organisms is also very low due to the levels of APH4 in most tissues that were below the levels of detection. The VIP3A protein was completely hydrolyzed in simulated mammalian gut fluids, which further demonstrated the lack of toxicity and allergenicity of the protein. The results of these studies led to the conclusion that the novel proteins VIP3A and APH4 in event COT102 cotton are neither toxic to non-target organisms, including mammalian species.

Links to Further Information Expand

Canadian Food Inspection Agency Food Standards Australia New Zealand Health Canada's Food Directorate Japan Food Safety Commission U.S. Department of Agriculture, Animal and Plant Health Inspection Service United States Department of Agriculture, Animal and Plant Health Inspection Service United States Food and Drug Administration

This record was last modified on Friday, August 4, 2017