<p style="text-align: justify;">Cotton (<i>Gossypium hirsutum</i> 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.</p>

<p style="text-align: justify;">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.</p>

<p style="text-align: justify;">Effective weed management is critical to cotton production. Weed control is more difficult in cotton than in other row crops, such as corn or soybean: cotton grows slowly early in the growing season and is thus less competitive with weeds. Competition from weeds has negative impacts on crop establishment, and ultimately, crop yield. Weeds can also be detrimental later in the growing season, interfering with harvesting, and resulting in a reduction in lint quality due to trash and possible staining. Weed control strategies include pre-plant tillage, crop rotation, and the use of herbicides. Annual grasses and some small seed broadleaf weeds are typically controlled with preplant incorporated herbicides (e.g., trifluralin, norflurazon, pendimethalin) while most broadleaf species are controlled with postermergence herbicides (<i>e.g.</i>, fluometuron, pendimethalin, pyrithiobac sodium). Crop rotation (<i>e.g.</i>, with soybean) prevents the build-up of problem weeds and herbicide biotypes by allowing the use of different herbicides.</p>

<p style="text-align: justify;">Roundup Ready&reg; Flex cotton (MON 88913) was developed to allow the use of glyphosate, the active ingredient in the herbicide Roundup&reg;, as a weed control option in cotton production. This genetically engineered cotton contains a novel form of the plant enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) that allows MON 88913 to survive otherwise lethal applications of glyphosate. The EPSPS gene introduced into MON 88913 was isolated from a strain of the common soil bacterium <i>Agrobacterium tumefaciens</i> strain CP4; the EPSPS enzyme expressed by this gene is tolerant to glyphosate. MON 88913 cotton contains two copies of the EPSPS gene to confer tolerance to glyphosate later in the growing season, specifically after the fifth true leaf stage.</p>

<p style="text-align: justify;">The EPSPS enzyme is part of the shikimate pathway, an important biochemical pathway in plants involved in the production of aromatic amino acids and other aromatic compounds. When conventional plants are treated with glyphosate, the plants cannot produce the aromatic amino acids needed for growth and survival. EPSPS is present in all plants, bacteria, and fungi. It is not present in animals, since these organisms are unable to synthesize their own aromatic amino acids. Because the aromatic amino acid pathway is not present in mammals, birds, or aquatic life forms, glyphosate has little, if any, toxicity for these organisms. The EPSPS enzyme is naturally present in foods derived from plant and microbial sources. MON 88913 was developed by introducing two CP4 EPSPS genes into the cotton variety &lsquo;Coker 312&rsquo; using <i>Agrobacterium</i>-mediated transformation.</p>

<p style="text-align: justify;">MON 88913 cotton was field tested at several locations in the United States and Puerto Rico from 2000 to 2003. Vegetative and reproductive growth, seed dormancy, emergence and germination, plant maturity, boll and seed yield, and fibre quality were found to be within the range for commercial cotton lines. Susceptibility to diseases and insects was not altered compared to conventional cotton varieties. MON 88913 did not demonstrate morphological, growth or seed dormancy characteristics such as those observed in weedy and invasive plant species.</p>

<p style="text-align: justify;">The potential for introgression of the glyphosate-tolerance trait from MON 88913 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 <i>G. hirsutum</i> (wild or under cultivation) and <i>G. barbadense</i> (cultivated Pima cotton), and is genetically compatible with <i>G. tomentosum</i>. Overall, the probability of gene transfer to wild species in unmanaged ecosystems is low due to the relatively isolated distribution of <i>Gossypium</i> species, different breeding systems, and genomic incompatibility. Assuming proximity, synchronicity of flowering and presence of insects, MON 88913 cotton could freely hybridize with other <i>G. hirsutum</i> 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 herbicidal applications of glyphosate.</p>

<p style="text-align: justify;">The food and livestock feed safety of MON 88913 cottonseed, cottonseed meal, and refined cottonseed oil was established based on several standard criteria. As part of the safety assessment, the nutritional composition of MON 88913 cottonseed, cottonseed meal and refined cottonseed oil was found to be equivalent to those components from conventional cotton as shown by the analyses of key nutrients including proximates (<i>i.e.</i>, moisture, crude protein, crude fat, ash, carbohydrates) acid detergent fibre, neutral detergent fibre and total dietary fibre, amino acid composition, fatty acid profiles, minerals (<i>e.g.</i>, calcium, phosphorus, magnesium), and vitamins E, as well as the antinutritional compounds gossypol, cyclopropenoid fatty acids and aflatoxins.</p>

<p style="text-align: justify;">The potential for toxicity and allergenicity of the CP4 EPSPS protein in MON 88913 was assessed from the following data and information: characterization of the protein demonstrating the lack of similarity to know toxins and allergens; data confirming the in vitro digestibility of CP4 EPSPS in simulated gastric fluids; the lack of acute oral toxicity in mice; and levels of natural toxicants. This information supports the lack of toxicity and allergenicity of MON 88913 compared to conventional cotton varieties.</p>
