INSERT INTO `gmcropdatabase_events_execsummaries` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(98, 113, '<p style="text-align: justify;">Maize, or corn (<i>Zea mays</i> L.) is grown commercially in over 100 countries with a combined harvest of nearly 700 million metric tonnes in 2006. The top five producers of maize in 2005 were the United States, China, Brazil, Argentina, and Mexico, accounting for 70% of world production. Maize is grown primarily for its kernel (grain), the majority of which is used for animal feed, but with significant amounts refined into products used in a wide range of food, medical, and industrial goods.</p>\n\n<p style="text-align: justify;">In the United States maize is typically used as animal feed, with roughly 70% of the crop fed to livestock, although an increasing share is now being used to produce ethanol for fuel. 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 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, car parts. Refined maize products are also used in bioproducts such as antibiotics.</p>\n\n<p style="text-align: justify;">Corn rootworm (<i>Diabrotica</i> spp.) is considered one of the most damaging insects pests of maize. The species of corn rootworm most prevalent in the United States are the northern corn rootworm (<i>Diabrotica barberi</i>) and the western corn rootworm (<i>D. virgifera</i>). The larvae of these beetles (coleopterans) feed on the corn roots. Feeding damage to the roots impedes the absorption of water and nutrients. Corn rootworms also feed on the brace roots and cause plant lodging. Adults feed on the silks thus interfering with pollination and seed set. Crop rotation is a recommended practice to reduce the population of these insects; thus, corn should not follow corn in a rotation. The protection offered by insecticides is limited: these will protect the crop from rootworm damage, but will only reduce a small percentage of the beetles from emerging.</p>\n\n<p style="text-align: justify;">The transgenic maize line MIR604 was genetically engineered to resist the western corn rootworm (<i>D. virgifera virgifera</i>), northern corn rootworm (<i>D. barberi</i>) and the Mexican corn rootworm (<i>D. virgifera zeae</i>) by producing an insecticidal protein. MIR604 contains two novel genes, a modified <i>cry3A</i> (<i>mcry3A</i>) gene encoding the mCry3A insecticidal protein and the <i>pmi</i> (<i>manA</i>) gene from <i>Escherichia coli</i> encoding the enzyme phosphomannose isomerase as a selectable marker.</p>\n\n<p style="text-align: justify;">The <i>mcry3A</i> gene encodes for a protein with a similar amino acid sequence to the Cry3Aa2 protein from <i>Bacillus thuringiensis</i> (Bt) subspecies <i>tenebrionsis</i>, with the inclusion of a protease cleavage site which results in a greater toxicity to certain species of corn rootworm. Cry proteins, of which mCry3A 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. mCry3A is lethal only when eaten by the larvae of coleopteran insects (<i>i.e. </i>, beetles) and exhibits no toxicity to other corn pests or non-target insects. There are no binding sites for the delta-endotoxins of <i>B. thuringiensis</i> on the surface of mammalian intestinal cells, therefore, livestock animals and humans are not susceptible to these proteins. The phosphomannose isomerase protein (encoded by the <i>pmi</i> gene) was used as a selectable marker as plants expressing this gene can utilise mannose as a primary carbon source, whereas cells lacking this gene fail to proliferate on mannose-based medium.</p>\n\n<p style="text-align: justify;">The food and livestock feed safety of MIR604 maize grain and forage was established based on several standard criteria, including the potential toxicity and allergenicity of the two proteins, mCry3A and phosphomannose isomerase, which was determined to be negligible. As part of the safety assessment, the nutritional composition of MIR604 grain and forage was found to be equivalent to conventional maize as shown by the analyses of key nutrients including proximates, fatty acid profiles, minerals and vitamins, as well as anti-nutrient compounds.</p>\n\n<p style="text-align: justify;">Field trials with MIR604 were conducted during 2002 and 2003 with few significant differences between MIR604 and non-transgenic controls. None of these differences were outside the range of values expected for maize hybrids. Disease susceptibility was not different to existing maize hybrids, neither was there any difference in resistance to pests, except corn rootworms. It was thus determined that there would be little impact on potential weediness of MIR604 and commercial cultivation of MIR604 is unlikely to harm non-target organisms.</p>\n', 'Enabled', NULL, '2013-08-30 17:23:42'),
(99, 126, '<p style="text-align: justify;">BW7 (Clearfield&trade;) bread wheat was not subject to regulation in any jurisdiction except Canada since the development of this herbicide-tolerant line did not employ recombinant DNA technologies. In Canada, regulatory approval is required for use in human food and livestock feed, and for environmental release.</p>\n\n<p style="text-align: justify;">Wheat (<i>Triticum</i> L.) is the of the most important cereal crops grown globally with a harvest of nearly 600 million metric tonnes in 2007. The major producers of wheat are the European Union, China, India, U.S.A., Russian Federation, Canada and Australia. Wheat is grown primarily for its grain and is a staple food for much of the world&rsquo;s population, although it also has other uses in the livestock feed and industrial sectors.</p>\n\n<p style="text-align: justify;">Commercial wheat is comprised mainly of two species: common, or bread wheat (<i>T. aestivum</i> L.) and durum wheat (<i>T. durum</i> Desf.). Bread wheat is classified into several types, based on the spring and winter forms of growth habit, and the hardness of the kernels. Winter wheat requires vernalisation to produce flowers, whereas spring wheat does not have this requirement. The hard types of bread wheat are high in protein, especially gliadins and glutenins. The high levels of these protein fractions in the flour impart elasticity to bread dough and allow it to expand during leavening and baking. Soft wheats are low in protein, and have low levels of gliadin and glutenin; these qualities are desirable in products such as cakes and pastries, and in unleavened breads. Durum wheat produces very hard, almost vitreous kernels due to its high protein content. This wheat is milled into semolina for the production of pasta and couscous.</p>\n\n<p style="text-align: justify;">Harvested wheat consists of a naked kernel, unlike other cereals such as rice, barley or oats that retain their hull (<i>i.e.</i>, the palea and lemma). The wheat kernel is loosely enclosed within the palea and lemma of each spikelet; these are eliminated as chaff during threshing. The wheat kernel is milled into white flour by removing the bran, aleurone layers and the germ prior to grinding; whole-wheat flour retains these fractions. By-products of wheat milling include: bran, germ, shorts and middlings. Some of these by-products are used as human food (<i>i.e.</i>, bran, germ), and others used as livestock feed. Grain that does not meet the grade for food use can be used as animal feed, mainly for poultry and swine, but also for cattle. Wheat can also be fed as forage, either as pasture prior to stem elongation, or as ensilage. Wheat is also used in the brewing and distilling industries and is the major source of starch used in Europe for bio-ethanol production.</p>\n\n<p style="text-align: justify;">Weeds are a major production problem in wheat cultivation. Weeds compete for light, water and nutrients, and can also cause lodging and problems with harvesting. The seeds of several weed species are almost impossible to clean out of harvested wheat (<i>e.g.</i>, <i>Avena fatua</i> L. wild oats), causing loss of quality and downgrading of the crop. Weeds can be managed using a combination of cultural practices (<i>e.g.</i>, seed bed preparation, use of clean [certified] seed, narrow row spacing, fertilizer banding), integrated weed management (<i>e.g.</i>, weed scouting, economic thresholds) and the use of herbicides. Depending on the weed species present, herbicides can be applied before the crop emerges (<i>e.g.</i>, amitrole, glyphosate, trifluralin), or after (<i>e.g.</i>, 2-4D, bromoxynil, dicamba, fenoxaprop-p-ethyl, MCPA, metsulfuron methyl). The build-up of weed populations can be stemmed by applying herbicides on summer-fallowed fields, and by practicing crop rotation, which allows the use of different herbicides. Rotating among herbicide groups also prevents the development of herbicide-resistant biotypes.</p>\n\n<p style="text-align: justify;">BW7 (Clearfield&trade;) bread wheat was developed to allow the use of imidazolinone herbicides as a weed control option in spring wheat production. The mode of action of imidazolinone herbicides consists of inhibiting the activity of acetohydroxyacid synthase (AHAS, sometimes referred to as acetolactate synthase or ALS), an enzyme in plants active in glycolysis and in the biosynthesis of the branched-chain amino acids isoleucine, leucine and valine. The result of the inhibition of AHAS activity is a decrease in protein synthesis and an accumulation of toxic levels of ?-ketoglutarate, which causes the eventual death of the plant. While unmodified wheat is not tolerant to imidazolinone herbicides, BW7 has been modified to survive an otherwise lethal application. BW7 was developed using chemically induced seed mutagenesis and whole plant selection procedures. The herbicide tolerance is due to a single point mutation in the AHAS gene, such that the resulting enzyme has a single amino acid substitution and is no longer affected by imidazolinone herbicides.</p>\n\n<p style="text-align: justify;">BW7 has been field tested in multiple locations in the United States from 2002 to 2005. Data collected from replicated field trials demonstrated that BW7 did not differ significantly from the parental line in terms of vegetative vigour, time to maturity, seed production (yield), disease resistance, and tendency to weediness.</p>\n\n<p style="text-align: justify;">The potential for transfer of the herbicide tolerant trait from BW7 wheat to other nonmodified wheat plants, or to wild relatives of wheat, has been investigated. Common wheat (<i>T. aestivum</i>) is primarily self-pollinating. While outcrossing can occur by wind-pollination, the rates are usually very low (&lt; 10%). Under the most ideal conditions, outcrossing will occur to nearby plants, but does not usually occur 3 m beyond the source plant. Given the variability of outcrossing rates among genotypes, an isolation distance of 30 m is required for certified seed production.</p>\n\n<p style="text-align: justify;">The potential for introgression of the novel trait into weedy relatives of wheat in Canada and the United States is also very low. Two species closely related to wheat are <i>Aegilops cylindria</i> Host (jointed goat grass) and <i>Agropyron repens</i> (L.) Beauv. (quackgrass). Both are introduced species and are considered weedy and invasive. Recent research has shown a possibility of hybridization between wheat and jointed goatgrass. Introgression of an herbicide tolerant trait from wheat into jointed goatgrass would confer an additional advantage to this weedy species.</p>\n\n<p style="text-align: justify;">The food and livestock safety of BW7 wheat was based on the evaluation of the similarity of AHAS, in structure and function, to the enzyme naturally present in food and livestock feeds and the lack of toxicity or allergenicity of the modified AHAS. The nutritional equivalence and wholesomeness of BW7 wheat compared to conventional wheat was demonstrated by the analysis of key nutrients in the grain including proximates (<i>e.g.</i>, crude protein, crude fat, crude fibre, ash, moisture), branched chain amino acids (valine, leucine and isoleucine), essential amino acids (cystine, methionine, threonine and lysine) fatty acid composition, vitamins and minerals, as well the levels of anti-nutrients (phytic acid and trypsin inhibitor). Significant differences were observed between BW7 and parental controls for some of the tested nutrients, but levels of all parameters measured were within the range of conventional bread wheat varieties.</p>\n', 'Enabled', NULL, '2013-08-30 17:30:16'),
(100, 127, '<p style="text-align: justify;">The genus <i>Prunus</i> comprises a diverse group of plants with many botanical species that have been cultivated for the last 3000 years and contains approximately 400 species of trees and shrubs. Many species and cultivars are grown for their edible fruits including almonds, apricots, cherries and peaches, in addition to plums and prunes. Other species are planted for their ornamental value and a few are commercially important for hardwood timber production.</p>\n\n<p style="text-align: justify;">Plum species are found native throughout the Northern hemisphere and the most important commercial species of plums are generally classified in two groups, the European plums (<i>Prunus domestica</i> L.) and related forms with a hexaploid chromosome number (2n=6x=48) and the Japanese plums (<i>Prunus salicina</i>) and their hybrids with diploid chromosome numbers (2n=2x=16). <i>P. domestica</i> is believed to have originated as a natural alloploid between <i>P. cerasifera</i> and <i>P. spinosa</i> and seems to have originated in Southern Europe or Western Asia around the Caucasus Mountains and the Caspian Sea.</p>\n\n<p style="text-align: justify;">World production of all plums was over nine million tons in 2005, with China accounting for nearly half of this total. Of the other countries in the top 10 producers, only the United States and Chile are from outside Europe. Within the United States, California is the leading producer of dried plums, accounting for 70% of the world exports for this commodity.</p>\n\n<p style="text-align: justify;">Plum pox virus (PPV) is the causal agent of Sharka disease, the most serious virus disease of stone fruits. PPV is spread from tree to tree by aphids and through infected budwood used for grafting. Symptoms of PPV infection include leaf and fruit yellowing, fruit deformation, premature fruit drop and tree decline. PPV has spread throughout Europe where it has destroyed over 100 million stone fruit trees and has also spread to India, Egypt, Lebanon, the Azores, Chile and has also been found in the US, where there is a strict quarantine and eradication program in Pennsylvania. Few highly resistant <i>Prunus</i> varieties have been developed through conventional breeding and thus genetically engineered resistance is considered to be an important option.</p>\n\n<p style="text-align: justify;">C5 is a genetically engineered plum clone containing the PPV coat protein gene that has been found to be highly resistant to PPV. The mechanism of resistance has been determined to be through post-transcriptional gene silencing as there is no protein expressed from the inserted coat protein gene. The resistance has proven to be highly stable, with field tests carried out over eight years in three European countries where the virus is present. No C5 trees in any of these field tests have become infected through natural aphid inoculation and graft inoculated trees show few and mild symptoms of the disease.</p>\n\n<p style="text-align: justify;">In addition to the PVP coat protein gene, C5 contains the <i>nptII</i> gene for resistance to the antibiotic Kanamycin as a selectable marker and the <uida> gene coding for the GUS enzyme, which was used as an assayable marker for the presence of the transgene. C5 was produced by <i>Agrobacterium</i>-mediated transformation of hypocotyl slices. Molecular analysis of C5 identified five separate transgene insertions, of which one is a complete insert and the others are either partial or re-arranged fragments of the T-DNA.</uida></p>\n\n<p style="text-align: justify;"><uida>C5 has been developed as a pre-emptive approach to the control of PPV should the disease become established in the United States. The are currently (2007) no plans to release this event commercially, but the event is available should the need arise and the resistance trait expressed in the event is available to breeders to improve other varieties of plum.</uida></p>\n', 'Enabled', NULL, '2013-08-30 17:30:44'),
(101, 128, '<p style="text-align: justify;">MIR604 X GA21 (OECD identifier: SYN-IR6&Oslash;4-5 x MON-&Oslash;&Oslash;&Oslash;21-9) maize is an F1 hybrid resulting from the hybridization of the coleopteran-resistant maize line MIR604 (SYN-IR6&Oslash;4-5) and the herbicide-tolerant maize line GA21 (MON-&Oslash;&Oslash;&Oslash;21-9). This stacked maize hybrid is a product of traditional plant breeding, and therefore is not automatically subject to regulation in all jurisdictions as are transgenic plants resulting from recombinant DNA technologies. Certain jurisdictions may request notification in advance of the release of a stacked hybrid, or may request information to conduct an environmental and food safety assessment. Examples of jurisdictions that require either notification or information about stacked hybrids prior to their release into the environment, and for use in human food and livestock feed are Japan and Korea.</p>\n\n<p style="text-align: justify;">The stacked hybrid MIR604 X GA21 expresses three novel proteins: the delta-endotoxin mCry3A which confers resistance to corn rootworm (<i>Diabrotica</i> species), the PMI protein which allows growth on mannose as a carbon source and is used as a selectable marker, and a modified EPSPS protein which confers tolerance to the herbicide glyphosate. The modified EPSPS protein is produced by the <i>mepsps</i> gene from GA21, the insecticidal protein mCry3A is produced by the <i>mcry</i>3A gene and PMI is produced by the <i>pmi</i> gene, both from MIR604. The novel traits of each parental line have been combined, through traditional plant breeding, to produce this new hybrid. For a full description of each parental line please refer to the individual product descriptions in the crop database for MIR604 and GA21.</p>\n\n<p style="text-align: justify;">The inserted genes and their gene products have a history of safe use, and have undergone review and approval by several regulatory agencies. No interactions among the gene products or negative synergistic effects are expected in the stacked hybrid. The mCry3A protein is not an enzyme and therefore does not affect plant metabolism. PMI has a high affinity for mannose-6-phosphate, converting it to fructose-6-phosphate which is directly utilised by the plant. The modified EPSPS has high affinity for its substrates phosphoenolpyruvate (PEP) and shikimate-3-phosphate, which are part of the shikimate metabolic pathway. PMI, EPSPS and mCry3A are therefore not expected to interact within, nor affect the metabolism of the stacked hybrid.</p>\n', 'Enabled', NULL, '2013-08-30 17:31:11'),
(102, 129, '<p style="text-align: justify;">BT11 x MIR604 (OECD identifier: SYN-BT&Oslash;11-1 x SYN-IR6&Oslash;4-5) maize is an F1 hybrid resulting from the hybridization of the lepidopteran-resistant and glufosinate-tolerant maize line BT11 (SYN-BT&Oslash;11-1) and the coleopteran-resistant maize line MIR604 (SYN-IR6&Oslash;4-5). This stacked maize hybrid is a product of traditional plant breeding, and therefore is not automatically subject to regulation in all jurisdictions as are transgenic plants resulting from recombinant DNA technologies. Certain jurisdictions may request notification in advance of the release of a stacked hybrid, or may request information to conduct an environmental and food safety assessment. Examples of jurisdictions that require either notification or information about stacked hybrids prior to their release into the environment, and for use in human food and livestock feed are Japan and Korea.</p>\n\n<p style="text-align: justify;">The stacked hybrid BT11 x MIR604 expresses four novel proteins: the delta-endotoxin Cry1Ab which confers resistance to the European Corn Borer and other lepidopterans, the PAT protein which confers tolerance to the herbicide glufosinate ammonium, the delta-endotoxin mCry3A which confers resistance to corn rootworm (<i>Diabrotica</i> species), and the PMI protein which allows growth on mannose as a carbon source and is used as a selectable marker. The insecticidal protein Cry1Ab is produced by the <i>cry</i>1Ab gene and PAT is produced by the <i>pat</i> gene, both from BT11, the insecticidal protein mCry3A is produced by the <i>mcry</i>3A gene and PMI is produced by the <i>pmi</i> gene, both from MIR604. The novel traits of each parental line have been combined, through traditional plant breeding, to produce this new hybrid. For a full description of each parental line please refer to the individual product descriptions in the crop database for BT11 and MIR604.</p>\n\n<p style="text-align: justify;">The inserted genes and their gene products have a history of safe use, and have undergone review and approval by several regulatory agencies. No interactions among the gene products or negative synergistic effects are expected in the stacked hybrid. The Cry1Ab and mCry3A proteins are not enzymes and therefore do not affect plant metabolism. PAT has a high affinity for L-Phosphinothricin, the active ingredient in glufosinate ammonium and PMI has a high affinity for mannose-6-phosphate, converting it to fructose-6-phosphate which is directly utilised by the plant. PMI, PAT, Cry1Ab and mCry3A are therefore not expected to interact within, nor affect the metabolism of the stacked hybrid.</p>\n', 'Enabled', NULL, '2013-08-30 17:31:39'),
(103, 130, '<p style="text-align: justify;">BT11 x MIR604 x GA21 (OECD identifier: SYN-BT&Oslash;11-1 x SYN-IR6&Oslash;4-5 x MON-&Oslash;&Oslash;&Oslash;21-9) maize is an F1 hybrid resulting from the hybridization of the lepidopteran-resistant and glufosinate-tolerant maize line BT11 (SYN-BT&Oslash;11-1), the coleopteran-resistant maize line MIR604 (SYN-IR6&Oslash;4-5) and the glyphosate-tolerant maize line GA21 (MON-&Oslash;&Oslash;&Oslash;21-9).. This stacked maize hybrid is a product of traditional plant breeding, and therefore is not automatically subject to regulation in all jurisdictions, as are transgenic plants resulting from recombinant DNA technologies. Certain jurisdictions may request notification in advance of the release of a stacked hybrid, or may request information to conduct an environmental and food safety assessment. Examples of jurisdictions that require either notification or information about stacked hybrids prior to their release into the environment, and for use in human food and livestock feed are Japan and Korea.</p>\n\n<p style="text-align: justify;">The stacked hybrid BT11 x MIR604 x GA21 expresses five novel proteins: the delta-endotoxin Cry1Ab which confers resistance to the European Corn Borer and other lepidopterans, the PAT protein which confers tolerance to the herbicide glufosinate ammonium, the delta-endotoxin mCry3A which confers resistance to corn rootworm (<i>Diabrotica</i> species), the PMI protein which allows growth on mannose as a carbon source and is used as a selectable marker, and a modified EPSPS protein which confers tolerance to the herbicide glyphosate. The insecticidal protein Cry1Ab is produced by the <i>cry</i>1Ab gene and PAT is produced by the <i>pat</i> gene, both from BT11, the insecticidal protein mCry3A is produced by the <i>mcry</i>3A gene and PMI is produced by the <i>pmi</i> gene, both from MIR604. The modified EPSPS protein is produced by the <i>mepsps</i> gene from GA21. The novel traits of each parental line have been combined, through traditional plant breeding, to produce this new hybrid. For a full description of each parental line please refer to the individual product descriptions in the crop database for BT11, MIR604 and GA21.</p>\n\n<p style="text-align: justify;">The inserted genes and their gene products have a history of safe use, and have undergone review and approval by several regulatory agencies. No interactions among the gene products or negative synergistic effects are expected in the stacked hybrid. The Cry1Ab and mCry3A proteins are not enzymes and therefore do not affect plant metabolism. PAT has a high affinity for L-Phosphinothricin, the active ingredient in glufosinate ammonium and PMI has a high affinity for mannose-6-phosphate, converting it to fructose-6-phosphate which is directly utilised by the plant. The modified EPSPS has high affinity for its substrates phosphoenolpyruvate (PEP) and shikimate-3-phosphate, which are part of the shikimate metabolic pathway. PMI, PAT, Cry1Ab, mCry3A and mEPSPS are therefore not expected to interact within, nor affect the metabolism of the stacked hybrid.</p>\n', 'Enabled', NULL, '2013-08-30 17:32:18'),
(116, 166, '<p>Abstract goes here. &nbsp;Blas...</p><br>', 'Enabled', '2013-08-09 12:49:40', '2013-08-23 00:19:19'),
(119, 98, '', 'Enabled', '2013-08-23 12:52:24', '2013-09-03 13:10:52'),
(120, 99, '', 'Enabled', '2013-08-29 19:05:09', '2013-08-29 19:05:09'),
(125, 169, '', 'Enabled', '2013-09-26 12:43:37', '2013-09-26 12:43:37'),
(123, 11, '', 'Enabled', '2013-09-03 11:25:26', '2013-09-03 11:25:26'),
(121, 107, '', 'Enabled', '2013-08-30 16:46:53', '2013-08-30 16:46:53'),
(122, 108, '', 'Enabled', '2013-09-02 13:10:02', '2013-09-02 13:13:42');



-- -----------------------------------------------------------------------------
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(1, 9, '<p style="text-align: justify;"><b>Dietary Exposure </b></p>\r\n\r\n<p style="text-align: justify;">Little whole kernel or processed maize is directly consumed by humans in comparison to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from MON810 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids will not be different from that for other commercially available field maize varieties.</p>\r\n\r\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\r\n\r\n<p style="text-align: justify;">Data on fatty acid profiles, protein content, amino acid composition, crude fibre, ash, phytate, and moisture content were provided for samples of MON810 grown in field trials in various locations in the United States and Europe. Comparisons of these parameters between MON810 and a non-transgenic control maize line did not reveal any biologically significant differences. The observed variations in nutritional composition were judged to arise from normal variability rather than as a result of the inserted novel traits. As a percentage of dry weight, the component analyses for line MON810, are approximately: protein 13.1%; fat 3.0%; moisture 12.4%; calories 408 Kcal/100g; ash 1.6%; and carbohydrate 82.4%.</p>\r\n\r\n<p style="text-align: justify;"><b>Toxicity</b></p>\r\n\r\n<p style="text-align: justify;">The trypsin-resistant Cry1Ab protein core expressed in insect-protected MON810 was identical to the same form of the protein contained in microbial <i>Bt</i> spray formulations that have been safely used in agriculture for more than 30 years. The low potential for toxicity of plant-expressed Cry1Ab protein was further demonstrated by a lack of amino acid sequence homology with known protein toxins, rapid digestion in simulated gastric juices, and lack of toxicity in feeding studies with laboratory animals. An acute oral toxicity study was done to assess the potential mammalian toxicity of Cry1Ab protein purified from <i>Escherichia coli</i> transformed with the same <i>cry1Ab</i> gene used to produce MON810. Bacterial expressed protein was used in these studies because insufficient amounts could be purified from plant tissue. Data demonstrating the molecular equivalence of bacterial and plant-expressed Cry1Ab protein were provided. The Cry1Ab core protein was administered to groups of ten male and female CD-1 mice in doses up to 4000 mg/kg body weight. These doses were well above the level of expression found in insect-protected maize plants and represented a 200-1000 fold excess over the level of exposure that would be predicted based on consumption of MON810 grain. As a control, equivalent groups of mice were administered either 4000 mg/kg bovine serum albumin or 66.66 mg/kg sodium carbonate solution (vehicle control). Clinical observations were performed and body weights and food consumption were determined. One female mouse belonging to the vehicle control died during the test &mdash; on day 1. The death of the control female was considered a result of the intubation procedure. As there were no deaths in other treated mice, or at higher exposure levels, the death was not considered to be treatment related. Mice were observed up to 9 days after dosing and no treatment related effects on body weight, food consumption, survival, or gross pathology upon necropsy were observed for mice administered the Cry1Ab test protein.</p>\r\n\r\n<p style="text-align: justify;"><b>Allergenicity</b></p>\r\n\r\n<p style="text-align: justify;">The Cry1Ab protein was evaluated for potential allergenicity by examining: (1) physiochemical characteristics; (2) amino acid sequence homology to known protein allergens; (3) digestibility; and (4) history of safe use of microbial insecticides containing this protein. Although the molecular weight of the Cry1Ab trypsin-resistant core protein, 63 kDa, was within the size range of known protein allergens, unlike many of these allergens it was not glycosylated. A search for amino acid sequence homology between the Cry1Ab protein and the amino acid sequences of 219 known allergens, using a database assembled from the public domain databases GenBank, EMBL, Pir and SwissProt, did not reveal any significant matches. Maize products are an important alternative to wheat flour for individuals afflicted with celiac 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. The digestibility of Cry1Ab protein was determined experimentally using <i>in vitro</i> mammalian digestion models. Purified Cry1Ab trypsin-resistant core protein (63 kDa) was added to simulated gastric and intestinal fluids and incubated at 37&ordm;C. The degradation of the protein in the digestion fluid was assessed over time by Western blot analysis and insect bioassay. In simulated gastric fluid, more than 90% of the Cry1Ab protein was degraded after 2 minutes incubation, while in simulated intestinal fluid the trypsin-resistant Cry1Ab core protein was not further degraded after more than 19 hrs incubation. This latter result was expected as serine proteases, such as trypsin, are the predominant proteolytic components of intestinal fluid. The source of the <i>cry1Ab</i> gene has a long history of use on food crops as a biopesticide and no evidence of adverse effects. This fact, combined with the lack of amino acid sequence homology between Cry1Ab protein and known allergens, and the rapid degradation of Cry1Ab protein in acidic gastric fluids, were sufficient to provide a reasonable certainty of lack of allergenic potential.</p>\r\n\r\n<p>&nbsp;</p>\r\n', 'Enabled', NULL, '2013-09-02 14:27:02'),
(2, 25, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification of Event 176 maize will not result in any change in the consumption pattern for this product. Consequently, dietary exposure to this product is anticipated to be the same as for other lines of commercially available maize.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Results from proximate analysis, and analyses of fatty acid profiles, carotenoids, and amino acid profiles showed that Event 176 did not differ significantly from non-transformed isogenic lines, and indicated that there were no unintended effects on metabolic pathways. Comparisons of protein, fat, fibre and ash concentration of corn grain and whole plant material from Event 176 and the non-transgenic counterpart showed occasional significant differences in fat and protein content and whole plant ash content. The observed variation described was judged to be normal variation rather than due to the inserted novel trait.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Direct toxicity studies conducted using Cry1Ab and PAT test material did not reveal any deleterious effects. The amino acid sequence of the truncated Cry1Ab protein expressed in 176 maize is closely related the sequence of the same proteins that are present in strains of <i>B. thuringiensis</i> that have been used for over 40 years as commercial organic microbial insecticides. An analysis of the amino acid sequences of the inserted Cry1Ab protein and the PAT enzyme did not show homologies with known mammalian protein toxins and they are not judged to have any potential for human toxicity.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The truncated Cry1Ab protein and the PAT enzyme expressed in 176 corn do not possess characteristics typical of known protein allergens. There were no regions of homology when the sequences of these introduced proteins were compared to the amino acid sequences of known protein allergens. Unlike known protein allergens, both of these proteins were rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric fluids. The Cry1Ab and PAT proteins are extremely unlikely to be allergenic.</p>\n', 'Enabled', NULL, '2013-08-29 22:31:02'),
(3, 49, '<p style="text-align: justify;">Maize line CBH-351 has only been approved in the USA for livestock feed use. The safety for use in animal feed was supported by the lack of toxicity of bacterial-expressed Cry9C protein in high oral dose feeding studies with laboratory animals, the low potential for toxicity of plant-expressed Cry9C protein demonstrated by a lack of amino acid sequence homology with known protein toxins and rapid digestion in simulated gastric juices.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Kernel composition, quality and other characteristics of CBH-351 maize were not significantly different from non-transgenic maize.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The low potential for toxicity of plant-expressed Cry9C protein was demonstrated by a lack of amino acid sequence homology with known protein toxins and the lack of toxicity in high oral dose feeding studies with laboratory animals.<br />\nA high-dose acute oral toxicity study was done to assess the potential mammalian toxicity to Cry9C protein present in CBH-351. Bacterial expressed protein was used in these studies because insufficient amounts could be purified from plant tissue. Data demonstrating the molecular equivalence of bacterial and plant-expressed Cry9C protein were provided.</p>\n\n<p style="text-align: justify;">An oral dose of the tryptic core Cry9C protein of at least 3,760 mg/kg was administered to 10 animals without mortality, demonstrating a high degree of safety for the protein. Transient weight losses were seen in three female treated rodents, with one not recovering her pre-dosing, pre-fast weight at 14 days after dose administration. The treated males showed no weight losses. Transient weight loss has been observed in similar studies conducted on other purified Cry proteins as well as microbial pesticides containing Cry proteins and is not considered a significant adverse effect.</p>\n\n<p style="text-align: justify;">As there was no indication of mammalian toxicity to the Cry9C protein from the studies submitted, there was no reason to believe there would be cumulative toxic effects on adults as well as on infants and children from residues of Cry9C and other substances with a common mechanism of toxicity.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The Cry9C protein was evaluated for potential allergenicity by examining the amino acid sequence homology to known protein allergens, digestibility, and the history of safe use of microbial insecticides containing this protein.</p>\n\n<p style="text-align: justify;">A search for amino acid homology between the Cry9C protein and the amino acid sequences of known toxins or allergens, using the databases PIR, Swiss-Prot and HIV AA, did not reveal any significant homology matches.</p>\n\n<p style="text-align: justify;">The digestibility of Cry9C protein was determined experimentally using an <i>in vitro</i> digestibility study. Results showed the Cry9C protein to be stable to pepsin digestion at pH 2.0 for 4 hours. The Cry9C protein was also found to be heat stable, not being affected by incubation at 90C for 10 minutes. The Cry9C protein contains a trypsin resistant core and is therefore stable to tryptic digest. Digestibility study showed the Cry9C protein to be stable to pepsin at pH 2.0.</p>\n\n<p style="text-align: justify;">The conclusion of the FIFRA Scientific Advisory Panel Report (December 2000) was that there is a medium likelihood that the Cry9C protein is a potential allergen based on the biochemical properties of Cry9C protein itself &ndash; not its levels in the food supply. Relative to the characteristics of known food allergens, there is no evidence disproving the potential allergenicity of Cry9C.</p>\n', 'Enabled', NULL, '2013-08-29 23:11:39'),
(4, 46, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Sugar beet is generally converted directly to refined white sugar (which is composed almost entirely of sucrose) through extensive purification processes. Analysis of highly refined sugar liquor and crystalline sugar from sugar beet showed that total protein within derivative food products ranged from 0.004 to 1.2 &micro;g per g. CP4-EPSPS and GUS proteins were expressed at low levels in the sugar beet root, and none of these proteins, including Protein 34550 were detected in refined sugar or molasses derived from sugar beet GTSB77.</p>\n\n<p style="text-align: justify;">Sugar beet pulp is a by-product that, in recent years, has been purified and used as an additive, at less than 1%, in some specific foods such as food fibre for breakfast cereals etc. While no direct analysis of these proteins was undertaken in soluble fibre derivatives, it was expected that they would be at negligible concentrations due to the processing steps involved.</p>\n\n<p style="text-align: justify;">It was concluded that little if any CP4-EPSPS or GUS protein would be consumed as a consequence eating food containing sugar derived from sugar beet GTSB77. Thus exposure to the novel proteins was likely to be extremely low.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Detailed compositional analyses conducted over multiple years and geographic regions (United States and Europe) were carried out to establish the nutritional adequacy of glyphosate-tolerant sugar beet GTSB77. The effect of glyphosate use on the composition of sugar beet was also examined. Analyses included crude ash, crude fibre, crude protein, carbohydrate and dry matter in both tops and roots (both raw and processed into brei powder used in sugar production). Additional quality components were measured in roots including, invert sugar (glucose + fructose) content, polarization (% sucrose), sodium, potassium and amino nitrogen. No biologically meaningful differences in any compositional and quality parameters relevant to food were identified between non-transgenic, control sugar beet and sugar beet GTSB77, both untreated or treated with glyphosate at recommended agronomic application rates. It is concluded that glyphosate-tolerant sugar beet is equivalent to other commercially available sugar beet with respect to composition and nutritional quality. No nutritional risks are posed by consuming food derived from glyphosate-tolerant sugar beet GTSB77.</p>\n\n<p style="text-align: justify;">The presence of naturally occurring toxins and allergens in glyphosate-tolerant sugar beet line GTSB77 was investigated. Saponins are the only known toxicants found in sugar beet and are actively eliminated in sugar processing. It was concluded that saponin levels in sugar beet GTSB77, both treated and untreated with glyphosate, are not considered to pose a risk to human health since: saponins are, in general, at very low levels in sugar beet tissues; sugar beet processing aims to eliminate saponins and other extraneous material from refined sugar products; and saponin levels in both glyphosate-treated and untreated GTSB77 do not differ significantly across seasons and sites, and fall within the range described for traditional sugar beet varieties in the literature.</p>\n\n<p style="text-align: justify;"><b>Toxicity data</b></p>\n\n<p style="text-align: justify;">The low potential toxicity and allergenicity of the CP4 EPSPS and GUS proteins were assessed. While no evidence of the presence of Protein 34550 was found in sugar beet GTSB77, toxicity studies of the protein were still carried out.<br />\nThere was no evidence to indicate that the CP4-EPSPS, GUS or Protein 34550 had the potential to be either toxic or allergenic to humans. Proteins from the EPSPS or GUS family of proteins are naturally present in our food supply or expressed in human intestinal microflora. The GOX like protein (Protein 34550) was not normally present in foods, but does not possess any of the characteristics common to many allergens or toxins or any significant sequence similarity to any known allergens or toxins. Furthermore, none of the proteins were detectable in the principal food components sugar and molasses, and in sugar beet pulp; CP4-EPSPS and GUS were negligible, detected at levels of 50 ppm and 1 ppm respectively. The levels of CP4-EPSPS and GUS proteins in sugar beet GTSB77 are extremely low in the root (0.005% and 0.00006% respectively) and Protein 34550 was undetectable at a limit of detection of 100 ppb.<br />\nIn order to assess the safety of these proteins, sufficient amounts of each respective protein were obtained by cloning the genes, CP4-EPSPS, gus and chimeric-gox, into <i>E. coli</i>. CP4-EPSPS and GUS proteins derived from <i>E. coli</i> were shown to be equivalent for safety assessment purposes. As no Protein 34550 was identified in sugar beet GTSB77 tissue, no equivalence of the <i>E. coli</i> cloned Protein 34550 could be established. PCR analysis using primers specific to the truncated <i>goxv247</i> gene did, however, showed that the sizes of the genes in both sugar beet GTSB77 and <i>E. coli</i> were equivalent at approximately 1273 bp.</p>\n\n<p style="text-align: justify;">To directly assess the potential toxicity of the CP4-EPSPS, GUS and 34550 proteins acute gavage tests were undertaken in mice using purified forms of each protein. Despite the experimental level of all three proteins being well in excess of the likely human dietary exposure factor, no mortality or morbidity resulted and there were no significant differences in terminal body weights between the treated and control groups. Upon necropsy, body cavities were opened and organs examined <i>in situ</i> and removed. No pathological findings attributable to the treatment with any protein were observed. All three proteins had no toxic effects on mice given acute doses of the equivalent bacterially produced proteins.</p>\n\n<p style="text-align: justify;">It was concluded that the food products derived from sugar beet GTSB77 should pose no greater risk as a source of toxins or allergens than food products derived from conventional sugar beets.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for the novel proteins to be allergenic was investigated using a number of criteria, including amino acid sequence homology with known allergens, history of use and common physicochemical properties of allergens, including the sensitivity to digestion by digestive enzymes.</p>\n\n<p style="text-align: justify;">Amino acid sequence similarity with known allergens was used as an indicator of the allergenic potential of novel proteins. The amino acid sequence of the CP4-EPSPS, GUS and 34550 proteins were compared to the amino acid sequences of 219 known allergens present in public domain databases (<i>e.g.,</i> GenBank, EMBL, Swissprot, PIR). Sequence similarity was defined as a sequence identity of greater than seven contiguous amino acids. No biologically significant similarity was found between any of the novel proteins with any of allergens listed in these databases.<br />\nAllergenic proteins in known allergenic foods (such as milk, soybeans and peanuts) exist as major proteins. There was very limited potential for the novel proteins from sugar beet GTSB77 to act as allergens in final food products as: none of the novel proteins could be detected in either sugar or molasses derived from sugar beet GTSB77, and dietary fibre refined from pulp derived from sugar beet GTSB77 would contain extremely low levels of CP4-EPSPS and GUS. Protein 34550 was not detected in pulp samples.</p>\n\n<p style="text-align: justify;">The CP4-EPSPS, GUS and 34550 proteins were degraded rapidly after exposure to simulated gastric fluid. Such rapid digestion would severely limit the amount of protein absorbed via the intestine and thus restrict any potential immunological response. The rate of degradation of these novel proteins was assessed in simulated gastric (SGF) and intestinal fluids (SIF). The degradation of C4 EPSPS, GUS and Protein 34550 were followed, either through Western blot or enzyme activity assays, in both SGF and SIF at 37C. CP4-EPSPS protein was shown to have a half-life of 15 sec in SGF and 10 min in SIF. No detectable GUS protein was present after 15 sec exposure to SGF and over 50% had been degraded in SIF after 60 to 120min. Over 90% of GUS activity had dissipated after 4 hr in SIF. Protein 34550 was degraded within 15 seconds exposure to SGF and within 60 seconds exposure to SIF, moreover no intermediate stable protein fragments larger that 2kD were generated by digestion of Protein 34550 in either SGF or SIF. On the basis of these data all three novel proteins were demonstrated to be readily digestible.</p>\n\n<p style="text-align: justify;">In summary, none of the novel proteins expressed in GTSB77 possess characteristics normally associated with protein allergens, and their potential for eliciting an allergenic response was judge to be extremely remote.</p>\n', 'Enabled', NULL, '2013-08-29 23:06:31'),
(5, 7, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\r\n\r\n<p style="text-align: justify;">Grain from DBT418 is intended primarily for animal feeding. However, such field maize may be dry- or wet-milled into various processed maize products for human food use. The human food uses of grain from DBT418 plants are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure of humans to grain from DBT418 will not be different from that for other commercially available field maize varieties.</p>\r\n\r\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\r\n\r\n<p style="text-align: justify;">Forage and grain from DBT418 maize hybrids were analyzed for nutritional composition and compared to the nutritional composition of non-transgenic versions of the same maize hybrids. Proximate and amino acid analyses were performed. Small differences between DBT418 plants and their non-transgenic counterparts were occasionally observed. However, the nutrient composition of DBT418 maize falls within the range of variability for the relevant nutrients reported for maize. The use of maize products derived from DBT418 would therefore have no significant impact on the nutritional quality of the North American food supply</p>\r\n\r\n<p style="text-align: justify;"><b>Toxicity</b></p>\r\n\r\n<p style="text-align: justify;">The amino acid sequences of the Cry1Ac and PAT proteins were compared to databases of known protein toxins and showed no homology with known mammalian protein toxins. An acute mouse toxicity study was performed using microbially-produced, purified Cry1Ac or PAT protein. The test protein was administered at doses up to 3325 mg/kg body weight and 2500 mg/kg body weight for Cry1Ac and PAT, respectively, without any observable adverse affects. Based on the results of these studies, the acute oral LD50 was estimated to be greater than 3325 mg of Cry1Ac or 2500 mg of PAT/kg body weight.</p>\r\n\r\n<p style="text-align: justify;"><b>Allergenicity</b></p>\r\n\r\n<p style="text-align: justify;">The likelihood of the Cry1Ac and PAT 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 propterties of known food allergens, such as stability to acid and/or proteolytic digestion, heat stability, glycosylation, and molecular weight. Neither the Cry1Ac protein or the PAT protein possessed these characteristics normally associated with food allergens. For example, studies demonstrated that the PAT enzyme was completely degraded within five minutes when subjected to typical mammalian gastric conditions and was thus digested as a conventional dietary protein.</p>\r\n', 'Enabled', NULL, '2013-09-02 14:23:30'),
(6, 6, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Maize lines T14 and T25 were 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 include products such as corn syrup and corn oil, bran, grits, meal and flour. There was no PAT protein detected in starch or oil. Neither was PAT protein detected in wet milled corn grain fractions with the exception of the bran. Wet milled bran and all of the dry milled corn fractions contained very low levels of the PAT protein (&lt; 0.00035% of crude protein). Overall, the dietary exposure of North Americans to grain from maize from lines T14 and T25 was anticipated to be the same as for other lines of commercially available field corn.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional analyses of maize grain from T14 and T25 derived lines and current commercial maize varieties were compared for compositional and nutritional parameters including moisture, crude fat, crude protein, crude fiber, ash, carbohydrates, mineral content (calcium and phosphorous), amino acid profile, phytates and oil composition. Overall protein content in the grain and whole plant was significantly higher in the transgenic lines compared to the unmodified controls. The statistical differences were explained by the fact that the transformed plant lines were not complete genetic isolines of the control plants and thus the variation arose from genetic differences unrelated to the transformation event. In all cases protein content was within the normal published range for maize. Similarly, an evaluation of the nutrient values determined that they were well within the range of nutrient values reported for corn grain. The use of corn grain from T14- and T25-derived maize lines was determined not to have a significant impact on the nutritional quality of the North American food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The low potential for toxicity of the PAT protein expressed in the transgenic maize lines T14 and T25 was demonstrated by examining the amino aid sequence homology, chemical characteristics of the protein and by acute oral toxicity testing in rats. The nucleotide sequence of the <i>pat</i> gene and the deduced amino acid sequence of the PAT protein were compared with sequences available for known toxins in the GenBank database and showed no significant homology with any known toxins or allergens. PAT protein expressed in bacterial systems was used as the test protein for mammalian feeding trials and studies were performed to demonstrate equivalence with the plant-expressed protein. The molecular weight and immunoreactivity of the PAT enzyme from the plant derived sources were similar to the PAT derived from a bacterial expression system. These similarities indicated that the PAT protein was unlikely to have been glycosylated or undergone other post translational modifications. An acute oral toxicity study demonstrated no evidence of toxicity for PAT protein when administered to rats at dietary concentrations up to 50,000 ppm for 14 days, which represents a concentration 6 orders of magnitude greater than that in grain from T14- and T25-derived maize lines.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The PAT enzyme expressed in T14- and T25-derived maize lines does not possess characteristics typical of known protein allergens and is extremely unlikely to be allergenic. There were no regions of homology when the sequences of the introduced protein was compared to the amino acid sequences of known protein allergens. There was no evidence found of post-translational modifications such as acetylation, glycosylation or phosphorylation of the PAT protein. Unlike known protein allergens, the PAT protein was rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric fluids. <i>In vitro</i> digestibility studies, under simulated mammalian gastric conditions, demonstrated that the PAT enzyme was inactivated within one minute and was rapidly degraded. No adverse effects have been reported to be associated with this enzyme.</p>\n', 'Enabled', NULL, '2013-08-29 20:57:01'),
(7, 16, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">BT11 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 kernel, compared with the major starch component. The level of the Cry1Ab protein in maize kernels, the only part of the plant used for human food, was very low - less than 5 ng/g fresh weight or 5 parts per billion. The dietary exposure will be lower than that experienced through eating products sprayed with <i>Bt</i>-based insecticides. Furthermore, the processing steps for maize would be expected to remove and/or destroy the Cry1Ab protein. Thus the level of Cry1Ab protein present in processed products derived from BT11 maize would be extremely low. Overall, the dietary exposure of people to insect resistant hybrids of BT11 maize was anticipated to be the same, or lower, as for other lines of commercially available field maize.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Detailed compositional analyses were carried out to establish the nutritional adequacy of BT11 maize, and to look for any unintended effects by comparing it to non-modified control lines. The nutritional composition of the ECB resistant maize hybrids was analysed at six locations for grain and silage. For the grain analysis, protein, oil, starch and fibre content of the ECB resistant maize lines were shown to be substantially equivalent to the untransformed controls. Silage samples from the ECB resistant maize hybrids had significantly higher levels of ADF and NDF than samples from the control lines, however the values were well within the normal range for corn silage. All other nutrients tested (protein, calcium, magnesium, phosphorus and potassium) were shown to be equivalent to their respective controls.<br />\nProximate analysis (protein, fat, fibre) was performed using Near Infrared Reflectance (NIR) technology. The method was conducted with appropriate calibration and statistical analysis, to show equivalence between the NIR technique and traditional chemistry. Sample falling outside the normal range using NIR were analysed using AOAC approved, traditional chemical methods. The proximate analysis of the ECB resistant maize hybrids gave values well within the published range for traditional maize cultivars.</p>\n\n<p style="text-align: justify;">Animal feeding studies demonstrated that were few significant differences in results between BT11 maize and non-transformed maize. Four separate studies were made with cattle. The first, a short-term experiment with dairy cattle was designed to study any carry over of the Cry1Ab and PAT proteins into milk. Neither protein could be detected in the milk of any animals fed whole-crop BT11 maize. The second longer-term trial with dairy cattle compared performance of animals fed BT11 maize or its conventional counterpart. There was no effect on dry matter intake, milk production, milk composition or a number of rumen parameters relating to feed utilization.<br />\nLaying hens were also fed a diet for 14 days incorporating 64% maize meal from BT11 maize. The diet with transgenic maize contained 240 - 263 ng/g Cry1Ab and 59 - 74 ng/g PAT. The control diet was slightly contaminated with transgenic kernels, accounting for 18 ng/g Cry1Ab. No significant differences were observed for feed intake, bodyweight, egg production, and egg weight. Egg whites, yolks and tissue samples (breast, thigh, liver) were analysed for Cry1Ab and PAT at the end of the experimental period. Neither protein was found in these tissues above the detection limits of 6 ng/g for CRY1Ab and 30 ng/g for PAT.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The potential for acute toxicity of the Cry1Ab and PAT proteins was assessed by evaluating physical and chemical characteristics of the proteins and also by acute oral toxicity in mice. Data were generated that demonstrated that the active Cry1Ab protein product of the inserted <i>cry1Ab</i> gene was equivalent to the protein contained in microbial <i>Bt</i> spray formulations that have been safely used in agriculture for more than 40 years. Studies on the Cry1Ab protein expressed in plants and the resulting proteolytic fragments were compared to the bacterial proteins and shown to be of similar molecular weight, amino acid sequence, immunological reactivity and susceptibility to trypsin digestion. The protein was not glycosylated and showed similar bioactivity and host range specificity to the native protein. The biological activity of the trypsinized Cry1Ab protein from the modified maize was the same as that of the native Cry1Ab on ECB, with a LC50 of 0.46-0.51 &micro;g/ml (f.w.) and an EC50 of 0.060-0.067 &micro;g/g (f.w.). After one week incubation in soil, 99% of the bioactivity of Cry1Ab in transgenic leaf tissue was lost due to aerobic degradation.<br />\nThe potential acute oral toxicity of Cry1Ab was assessed in mice. High oral dose feeding studies were conducted on mice fed Cry1Ab protein, or its truncated form, at up to 4000 mg/kg bodyweight without toxic effects. These results were consistent with other studies on the acute toxicity of Cry1Ab in mice and in rabbits and did not demonstrate any potential mammalian toxicity from Cry1Ab protein.</p>\n\n<p style="text-align: justify;">The toxicity of PAT protein was assessed using similar animal studies. Results from acute oral toxicity testing in mice did not indicate any toxic effects. A comparison of the amino acid sequence of the PAT protein to a database of known toxins demonstrated that it does not share any significant similarity with any known protein toxins. The sequences were obtained from the GenBank, EMBL, Swissprot and PIR databases. Furthermore, the PAT enzyme has very specific enzymatic activity and does not possess proteolytic or heat stability, and does not affect plant metabolism. Acetyltransferases are common enzymes in bacteria, plants and animals and no toxic or allergic effects were expected.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for the novel proteins Cry1Ab and PAT to be allergenic was investigated using a number of criteria, including amino acid sequence homology with known allergens, history of use and common physicochemical properties of allergens, including the sensitivity to digestion by digestive enzymes.<br />\nThe deduced amino acid sequences of the introduced proteins were compared to 219 known allergens present in public domain databases (GenBank, EMBL, Swissprot, PIR) and no homologies were detected. Unlike known protein allergens, studies have shown that Cry1Ab proteins were rapidly inactivated when subjected to simulated mammalian gastric fluids. Similarly, the PAT protein was found to be rapidly digested in conditions that mimic human digestion. Also, PAT was found to be present at very low levels, if at all, in maize kernels.</p>\n\n<p style="text-align: justify;"><b>Herbicide Residue Analysis</b></p>\n\n<p style="text-align: justify;">The principal residue identified in transgenic BT11 maize plants after post-emergence use of glufosinate ammonium was N-acetyl-glufosinate with lesser quantities of glufosinate and 3-[hydroxy(methyl)phosphinoyl]propionic acid (MPP) which was also found in non-transgenic plants. In maize grain, which exhibits much lower residues than the other plant parts, the principal residue identified was MPP with lesser amounts of N-acetyl-glufosinate. About 80 field trials in Europe were conducted with different application rates and residues in harvested grain for each metabolite was below 0.05 mg/kg. In green maize, forage and fodder, higher residues can occur. The glufosinate-derived residues do not concentrate in any maize processed fraction, which are relevant food or feed items. These include flour, starch, grits and oil. Residues are not detectable in crude and refined oil. In ruminant and poultry feeding studies no detectable residues were found in meat, milk or eggs at the dose calculated to represent the highest residues in livestock feed under Good Agricultural Practices and taking into account the potential use of glufosinate herbicide in several tolerant crops. It was concluded, on the basis of the available data, that residues of glufosinate ammonium and its metabolites, N-acetyl-glufosinate and 3-[hydroxy(methyl)phosphinoyl]propionic acid (MPP) expressed as glufosinate free acid equivalents, were below 0.1 mg/kg maize grain. In food of animal origin from livestock animal fed with feedstuffs after application of glufosinate herbicide in tolerant maize no residues above the limit of determination are to be expected.</p>\n', 'Enabled', NULL, '2013-08-29 22:06:42'),
(8, 1, '<!-- Generated by XStandard version 3.0.0.0 on 2012-10-23T14:40:19 -->\n<p style="text-align: justify;"><strong>Dietary Exposure</strong></p>\n\n<p style="text-align: justify;"><br />\nAs GA21 maize was intended primarily for use in livestock feed, the level of dietary exposure to the mEPSPS protein was predicted to be very low. 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 kernel, compared with the major starch component. Overall, the dietary exposure of consumers in Canada and the United States to grain from GA21 maize was anticipated to be the same as for other lines of commercially available field corn.</p>\n\n<p style="text-align: justify;"><strong>Nutritional Data</strong></p>\n\n<p style="text-align: justify;">Maize line GA21 and non-transformed control lines were grown at five different locations in 1996. Several samples of both forage material and grains were collected and analyzed. Forage was analyzed for proximate composition: ash, calcium, carbohydrates, fibre [acid detergent fibre (ADF) and neutral detergent fibre (NDF)] moisture, and phosphorus, protein, and fat. Grains were analyzed for protein, fat, ash, carbohydrate (calculated), fibre (ADF and NDF), amino acid and fatty acid composition, calcium and phosphorus. Complementary analyses were conducted on trace elements, trypsin inhibitors, phytic acid and Vitamin E. There were no significant differences in nutrient composition between GA21 and commercial maize varieties in either the grain or forage material.<br />\nThe data assessed from animal feeding studies clearly demonstrated the nutritional equivalence of grain from GA21 to isogenic material, on the basis of growth performance and body composition of broiler chickens receiving GA21 maize compared to isogenic grain for 40 days.</p>\n\n<p style="text-align: justify;"><strong>Toxicity</strong></p>\n\n<p style="text-align: justify;">Because the amino acid sequence of the mEPSPS was 99.3% identical with the sequence of the wild-type enzyme the amino acid substitutions were not predicted to result in an increased potential for toxicity. Furthermore, the amino acid sequence of the inserted mEPSPS enzyme was compared to that of known protein toxins listed in the PIR, SwissProt, EMBL and GenBank genetic databases. Based on these computer searches the mEPSPS protein did not show homologies with known toxins and was judged not to have any potential for human toxicity.<br />\nThe two putative open reading frames (ORFs) identified proximal to the mEPSPS insert were both derived from maize sequences and assessed for potential toxicity. Northern blot analysis of poly(A+) RNA from GA21 and control lines demonstrated that transcription of these ORFs did not occur in maize line GA21. Sequence analysis indicated no homologies with known toxins or allergens.</p>\n\n<p style="text-align: justify;">Bacterial-expressed mEPSPS was further evaluated for acute oral toxicity in a laboratory animal feeding trial. The test protein was administered by a single oral gavage to ten male and ten female CD-1 mice at doses corresponding to 3.7, 11.8 and 45.6 mg/kg. The highest dose of 45.6 mg mEPSPS/kg body weight was claimed to be at least 500-fold higher than the likely human exposure. A control group of ten mice/sex was administered only the carrier substance, at the same delivery volume as the test substance. An additional control group of ten mice/sex was administered bovine serum albumin (BSA) in the same carrier substance at the highest target dose (45.6 mg/kg). At defined stages throughout the duration of the study, clinical observations were performed for mortality and signs of toxicity, and body weights and food consumption measured. At the termination of the study (day 13-14), animals were sacrificed, examined for gross pathology and numerous tissues were collected and saved.</p>\n\n<p style="text-align: justify;">It was concluded that there was no evidence of toxicity in mice following a single oral dose of 45.6 mg/kg mEPSPS protein. The results of the study showed no statistically significant differences in group mean body weights, cumulative weight gains or food consumption in either males or females at any level of either the BSA control or test material, when compared with the respective carrier control group. All animals survived to the end of the study, and there were no clinical signs observed that could be related to the test material.</p>\n\n<p style="text-align: justify;"><strong>Allergenicity</strong></p>\n\n<p style="text-align: justify;">The wild-type maize EPSPS enzyme has not been associated with any allergic effects, nor is its amino acid sequence homologous with any know protein allergens. The near complete identity (99.3%) between the amino acid sequences of the mEPSPS and wild-type EPSPS enzymes was expected to ensure a lack of allergenicity of the novel protein. The amino acid sequence of the inserted mEPSPS enzyme was compared to a database of 219 known allergens and gliadin sequences constructed from public domain databases. There were no significant sequence similarities discovered between mEPSPS and known allergens and gliadins. Data presented also showed that the protein was not glycosylated, a property common to many allergens. Also, unlike common allergens the mEPSPS protein was present at very lows levels (Unlike known protein allergens, the mEPSPS was rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric or intestinal fluids. EPSPS isolated from leaves of GA21 maize, including mEPSPS (70% of activity), was rapidly degraded <em>in vitro</em> in artificial human gastric and intestinal fluids. The results of these experiments demonstrated that the mEPSPS protein was no longer detectable after 15 seconds in the gastric system and within one minute in the intestinal system.</p>\n\n<p style="text-align: justify;">Together these results strongly supported the conclusion that maize line GA21 expressing mEPSPS did not pose any greater risk than conventional maize, with respect to potential allergenicity.</p>\n', 'Enabled', NULL, '2013-08-29 20:36:32'),
(9, 51, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The MON80100 line of transgenic maize is not a sweet maize, but rather, a field maize intended mainly for use in animal feed. However, some human food uses are relevant for field maize. The MON80100 maize hybrids would be either dry or wet-milled into various processed maize products. The genetic modification of MON80100 maize will not result in any change in the consumption pattern for this product. Consequently, dietary exposure to this product is anticipated to be the same as for other lines of commercially available field maize.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from transgenic MON80100 maize and non-transgenic maize did not reveal any significant differences in the levels of protein, fat, fibre and starch. Similarly, the levels of micronutrients including calcium, phosphorus, potassium and magnesium were within the established ranges for maize. Feeding trials with rats, catfish and quail in which raw or processed maize meal from transgenic MON80100 was incorporated into the diet, did not reveal any significant differences in weight gain, food consumption or gross pathology between test and control subjects. The consumption of products from MON80100 will have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The trypsin-resistant Cry1Ab protein core expressed in insect-protected MON80100 was identical to the same form of the protein contained in microbial <i>Bt</i> spray formulations that have been safely used in agriculture for more than 40 years. The low potential for toxicity of plant expressed Cry1Ab protein, and CP4 EPSPS and glyphosate oxidoreductase enzymes was demonstrated by a lack of sequence homologies with known mammalian protein toxins.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The Cry1Ab protein, CP4 EPSPS and glyphosate oxidoreductase enzymes do not possess characteristics typical of known protein allergens. There were no regions of homology when the sequences of three introduced proteins were compared to the amino acid sequences of known protein allergens. Unlike known protein allergens, these proteins were rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric or intestinal fluids.</p>\n', 'Enabled', NULL, '2013-08-29 23:14:37'),
(104, 99, '', 'Enabled', '2013-08-29 19:05:09', '2013-08-29 19:05:09');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(10, 12, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">MON809 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. The potential 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 kernel, compared with the major starch component. Overall, the dietary exposure of consumers in the United States and Canada to insect resistant hybrids of MON809 maize was anticipated to be the same as for other lines of commercially available field maize.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The nutritional quality of grain from MON809 maize was similar to that of grain from an equivalent non-transgenic line and to grain currently available in commerce. Grain was subjected to proximate analysis (<i>e.g.</i>, ash, moisture content, crude protein, crude fat), amino acid and fatty acid composition. Some minor differences were observed between MON809 and an equivalent non-transgenic line, but the levels were within the range of variation normally observed in the commercial grain supply and were attributed to variations in the plant genotypes rather than to the presence of the introduced genes.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Data were submitted that demonstrated that the active Cry1Ab protein product of the inserted <i>cry1Ab</i> gene was equivalent to the protein contained in microbial <i>Bt</i> spray formulations that have been safely used in agriculture for more than 40 years. Studies on the Cry1Ab protein expressed in plants and the resulting proteolytic fragments were compared to the bacterial proteins and shown to be of similar molecular weight, amino acid sequence, immunological reactivity and trypsin resistance. The protein was not glycosylated and showed similar bioactivity and host range specificity to the native protein. The Cry1Ab and CP4 EPSPS proteins should pose no risks for consumption of products produced from insect resistant maize. The introduced proteins were compared to databases of known protein toxins and neither showed any significant amino acid sequence similarity to known protein toxins. Neither protein was toxic when fed to mice.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The Cry1Ab and CP4 EPSPS proteins are extremely unlikely to be allergens. The deduced amino acid sequences of the introduced proteins were compared to sequences of known allergens contained in the public domain databases GenBank, EMBL, Pir and SwissProt. No significant sequence homologies were detected. Neither the Cry1Ab and CP4 EPSPS protein originated from an allergenic source, or were structurally similar to known allergens. EPSPS is ubiquitous in bacteria, plants and animals and no toxic or allergenic effects have ever been reported. In addition, the potential for allergenicity was assessed based upon the characteristics of known food allergens (stability to digestion, stability to processing, abundance in foods). Protein allergens are normally resistant to digestion unlike the Cry1Ab protein that was shown to degrade readily in simulated gastric fluid. Similarly, data were presented showing that the CP4 EPSPS enzyme was rapidly inactivated by heat and by digestion in simulated mammalian gastric fluid.</p>\n\n<p style="text-align: justify;">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 corn products to these individuals, a sequence similarity search was conducted and no amino acid sequence homologies between the Cry1Ab protein and gliadins were detected.</p>\n', 'Enabled', NULL, '2013-08-29 21:57:49'),
(11, 72, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Grain from maize line MON832 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 kernel, compared with the major starch component. Overall, the dietary exposure of consumers in the United States and Canada to grain from MON832 maize was anticipated to be the same as for other lines of commercially available field corn.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The major components of maize grain and forage from MON832 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 MON832 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 MON832 and an appropriate control. Based on these compositional data, it was concluded that there were no significant differences between the forage from line MON832 and the control line.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The low potential for toxicity of transgenic maize line MON832 was demonstrated by examining the amino aid sequence homology, protein characterization, digestive fate studies in simulated gastric and intestinal fluids and acute oral toxicity in mice. Using sophisticated computerized search capabilities, the evidence showed that the CP4 EPSPS and GOX proteins did not show meaningful amino acid sequence homology when compared to known allergens or protein toxins. These studies support the safety of the proteins and are consistent with the history of safe presence and ubiquitous distribution of <i>Agrobacterium</i> and <i>Achromobacter</i> spp. in the soil. An acute mouse toxicity study further indicated that there were no toxic effects caused by CP4 EPSPS or GOX proteins administered by oral gavage, as measured by the absence of treatment related adverse effects in mice.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The CP4 and GOX proteins are not likely to be toxic or allergenic. The amino acid sequences of both proteins were compared with known toxins and allergens did not show meaningful amino acid sequence homology. In addition, the potential for allergenicity was assessed based upon the characteristics of known food allergens (stability to digestion, stability to processing). Unlike known protein allergens, studies have shown that the CP4 and GOX proteins are rapidly degraded and their enzymatic activity lost under conditions that simulate mammalian digestion.</p>\n', 'Enabled', NULL, '2013-08-29 23:43:12'),
(12, 5, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;">Data were generated that demonstrated that the active Cry1Ab protein product of the inserted <i>cry1Ab</i> gene was equivalent to that produced in the naturally occurring bacterium <i>Bacillus thuringiensis</i> 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.</p>\n\n<p style="text-align: justify;">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.<br />\nA 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.<br />\nSimilarly, the CP4 and GOX proteins did not show meaningful amino acid sequence homology when compared to known allergens or protein toxins. The Roundup Ready&reg; 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.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;">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.<br />\nUnlike 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.<br />\nMaize 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.</p>\n', 'Enabled', NULL, '2013-08-29 20:43:31'),
(13, 23, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Typically, canola oil is used by itself as a salad oil or cooking oil, or blended with other vegetable oils in the manufacture of margarine, shortening, salad oil and cooking oils. Refined edible canola oil consists of purified triglycerides (96-97%) and does not contain any detectable protein, hence no amounts of CP4 EPSPS or GOX proteins were detected in the refined oil of GT73 canola. The genetic modification of GT73 canola will not result in any change in the consumption pattern for this product. As the introduced gene products were not detectable in the refined oil produced from transgenic canola, there is little or no anticipated human exposure to these proteins</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from transgenic GT73 canola and non-transgenic canola did not reveal any significant differences in the levels of crude protein, crude fat, crude fibre, ash and gross energy in either whole seed or processed meal. The fatty acid composition of oils and levels of the shikimate pathway aromatic amino acids phenylalanine, tyrosine and tryptophan extracted from both transgenic GT73 and non-transgenic canola was statistically the same and, in the case of fatty acids, within the normal range for canola oil. These results collectively demonstrated that the introduction of the novel genes in GT73 should not result in any secondary effects impacting on composition or nutritional quality. Furthermore, the transgenic line GT73 meets the standards for canola oil in Canada of containing less than 2% erucic acid and less than 30 micromoles/g glucosinolates in the oil-free meal. It was determined that the consumption of refined oil from GT73 would have no significant impact on the nutritional quality of the food supply in the United States and Canada.</p>\n\n<p style="text-align: justify;">Several animal feeding studies were conducted to demonstrate the wholesomeness of canola meal. Canola meal is used only for animal feed and is not considered a human food fraction. The feeding studies were conducted to establish the nutritional adequacy of canola meal for animal feeds and represented a worst case scenario in terms of canola consumption by humans. These studies included a four-week rat study on processed and unprocessed meal, a ten-week trout study on processed meal and a five-day quail (Northern Bobwhite) study on unprocessed meal. The studies all supported the safety of meal from glyphosate-tolerant canola as a component in animal feed.</p>\n\n<p style="text-align: justify;">The rat feeding study examined six week-old Sprague-Dewley rats (10/sex/group) fed either 0, 5 or 15% w/w ground (unprocessed) and processed (toasted and defatted) glyphosate-tolerant canola (GT73 and GT200) and &#39;Westar&#39; canola meal and a diet control (commercial rodent chow with no added canola meal). The study determined that rats fed on diets with unprocessed canola seed had relative liver and kidney weights 5 - 20% greater compared to the diet controls. However, there were no differences in absolute or relative organ weights between the glyphosate-tolerant canola and parental line groups. When fed processed canola meal, there were no meaningful differences observed in body weights and body weight gains between groups fed processed glyphosate-tolerant canola meal, parental line canola meal and a control diet. Liver weights, however, increased approximately 12-16% for both sexes fed 15% GT73 meal. The increase in liver weight was attributed to a higher level of alkyl glucosinolate toxicants in the glyphosate-tolerant canola line GT73 which was 4 g/kg compared to 1.8 g/kg for the parental line. The higher level of glucosinolates present in glyphosate-tolerant canola was not attributed to the genetic modification.</p>\n\n<p style="text-align: justify;">The quail feeding study examined thirty northern bobwhite (<i>Colinus virginianus</i>) chicks fed diets for five days and observed for a further three days. Treatment groups were fed a control diet, glyphosate-tolerant canola (both line GT73 and GT200) or the parental line &#39;Westar&#39;, where canola was incorporated at a rate of 20% of the total weight of the diet. The study did not find any significant effects on body weight or feed consumption between birds in the control or treatment groups. There were no mortalities or overt signs of toxicity in either treatment or control groups.<br />\nSimilarly a trout feeding study examined triplicate groups of 15 fish rainbow trout (<i>Oncorhynchus mykiss</i>) fed canola meal at 0, 5, 10, 15 or 20% weight of the dry diet for 10 weeks (<i>i.e.</i>, 45 fish/treatment).There was statistical overlap in weight gain of fish fed each dietary treatment and no differences were detected between glyphosate-tolerant canola (both line GT73 and GT200) diets and controls. Fish fed the glyphosate-tolerant canola did not exhibit any adverse effects.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">It was determined that there were no toxicity or allergenicity concerns with GT73, since refined canola oil is the only product for human consumption and does not contain any detectable amount of protein. The absence of toxicity was further demonstrated by examining the amino aid sequence homology and the physiochemical characteristics of the CP4 EPSPS and GOX proteins, and acute toxicity study in mice.</p>\n\n<p style="text-align: justify;">The deduced amino acid sequences of both the CP4 EPSPS and GOX proteins were compared to the amino acid sequences of 1935 known protein toxins. No significant similarities were found other than would be expected given that certain functional domains are generally conserved between proteins.</p>\n\n<p style="text-align: justify;">The CP4 EPSPS enzyme belongs to the same family of EPSPS enzymes that occur in plants, fungi and bacteria. The EPSPS proteins are naturally present in foods derived from plants and microbes and have no history of being toxic or allergenic. Similarly, the <i>gox</i> gene was sourced from a common soil bacterium, which has no history of pathogenicity. The GOX enzyme degrades glyphosate and experiments demonstrated that the enzyme displayed a narrow substrate specificity, and appeared not to have any secondary effects on other plant specific pathways.</p>\n\n<p style="text-align: justify;">The acute oral toxicity of CP4 EPSPS, GOX and GOXv247 proteins, was studied in groups of ten CD-1 mice/sex in order to directly assess the potential for toxicity associated with these proteins. Based on previously assessed studies, there were no adverse effects or mortalities noted in mice administered CP4 EPSPS protein by gavage at doses up to 572 mg/kg. Similarly, no adverse effects were observed in mice administered the GOX protein by gavage at doses up to 100 and 104 mg/kg for GOX and GOXv247 respectively. The doses were well above the level of expression of the proteins found in glyphosate-tolerant canola plants, estimated to be a 1300-fold increase of CP4 EPSPS and 5000-fold increase of GOX. Clinical observations observed up to 9 days after dosing showed no signs of toxicity (<i>i.e.</i>, no adverse effects for either protein on body weight, food consumption, survival, or gross pathology).</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The possibility of exposure to CP4 EPSPS and GOX is significantly limited by the combined facts that these proteins are present at low levels in leaf tissue and are absent in refined oil. The low potential for allergenicity was further demonstrated by examining the amino aid sequence homology and a study on the digestibility of the CP4 EPSPS and GOX proteins.</p>\n\n<p style="text-align: justify;">The amino acid sequence of the CP4 EPSPS and GOX proteins were compared to the amino acid sequences of 219 known allergens present in public domain databases (<i>e.g.</i>, GenBank, EMBL, Swissprot, PIR). No significant similarities (<i>i.e.</i> a sequence of more than 8 consecutive amino acids) were found with any of these known allergens.<br />\nThe study of the digestibility of both proteins in model digestion systems was done <i>in vitro</i> using simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) as mammalian digestion models. The exposure of CP4 EPSPS and GOX proteins to SGF and SIF was conducted over a series of timed incubations at 37&deg;C. The products of the digestion were analyzed using gel electrophoresis, Western blot analysis and enzymatic activity assays. From the simulated digestion experiments and Western blot analyses, the CP4 EPSPS protein had a half-life of less than 15 seconds in the gastric system and 10 minutes in the intestinal system. The GOX protein had a half-life of less than 30 seconds in the intestinal system as determined by Western blot analyses. In summary, both the CP4 EPSPS and GOX proteins were digested by proteases present in the mammalian digestive system, suggesting that they would not survive peptic and tryptic digestion or the acidic conditions of the human digestive system.</p>\n', 'Enabled', NULL, '2013-08-29 22:28:07'),
(14, 13, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Maize line MS3 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 include products such as corn syrup and corn oil, bran, grits, meal and flour. The human food uses of MS3 maize grain were not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure of people to grain from MS3-derived maize hybrids was not prediced to differ from that for other commercially available field corn varieties. Furthermore, since neither of the introduced proteins were detected in the corn grain, there would be no dietary exposure to these introduced proteins.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The composition of grain from MS3-derived hybrid maize was compared to grain from non-transgenic maize. Parameters such as moisture, fibre, fat protein, ash, starch, oil, fatty acids and the amino acid composition were compared with no significant differences being observed. The use of grain from MS3-derived maize hybrids would therefore have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The low potential for toxicity of transgenic maize line MS3 was demonstrated by examining the amino aid sequence homology and the characteristics of the proteins. An amino acid sequence comparison of the barnase enzyme with the sequences of known protein allergens and toxins in three public domain databases did not reveal any significant homologies, other than with ribonucleases from other bacilliform bacteria. Similar comparative analyses were completed for PAT enzyme. The amino acid sequence of PAT enzyme did not show significant homologies with any toxins or allergens, except with other phosphinothricin acetyltransferases originating from different organisms.<br />\nThe full nucleotide sequence of the barnase gene was provided. The RNAse enzyme, encoded by the barnase gene, was a small single-domain protein, containing no disulfide bonds, metal-ion cofactors or other non-peptide components. When heated, it unfolded completely into an inactive form.</p>\n\n<p style="text-align: justify;">No toxic or allergic effects were expected from PAT as acetyltransferases are ubiquitous in nature, do not possess proteolytic or heat stability and are highly substrate specific. PAT has a extremely high substrate specificity for L-PPT and dimethylphosphinothricin (DMPT), and experimental data clearly showed that neither L-PPT&#39;s analog L-glutamic acid, D-PPT, nor any other amino acid can be acetylated by the PAT enzyme.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The barnase RNAse and PAT enzymes are not likely to be allergenic. In addition to the amino acid sequence homology searches describe above, the potential for allergenicity of the PAT enzyme was assessed based upon the characteristics of known food allergens (stability to digestion, stability to processing). Unlike known protein allergens, these studies demonstrated that the PAT enzyme was rapidly inactivated when subjected to typical mammalian stomach conditions. In summary, the barnase RNAse and PAT enzyme were not derived from allergenic sources, do not share amino acid sequence homology with known allergens, and do not possess the physiochemical properties (heat and proteolytic digestion stability) normally associated with allergens.</p>\n', 'Enabled', NULL, '2013-08-29 22:00:11'),
(15, 27, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Because virtually no protein is present in the oil extracted from the plants, the potential for human exposure is exceedingly low. Furthermore, the amounts of PAT protein present in seed-meal fed to animals would be too low to cause concern. Additionally, the barnase RNAse and its inhibitor encoded by barnase and barstar genes, respectively, were not detected in dry seeds. As the introduced gene products were not detectable in the refined oil produced from transgenic canola, there will be no human exposure to these proteins based on normal consumption patterns.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The composition of refined canola oil from MS8 x RF3 hybrid canola was compared to that for refined oil from non-transgenic canola. Some statistical differences in fatty acid composition were noted in the comparison, however, the fatty acids for the transgenic lines, including the erucic acid content of the oil, were within the normal range for canola oil fatty acids. Processing according to protocols mimicking industrial practices (including tempering, flaking, cooking, pressing, desolventizing oil and meal, oil blending, degumming, oil refining, water washing, bleaching, hydrogenation and deodorizing) further demonstrated that the composition and physical characteristics of the oil from MS8 x RF3 hybrids and control canola varieties were equivalent. The use of refined oil from MS8 x RF3 canola hybrids would therefore have no significant impact on the nutritional quality of the food supply. Similarly, the glucosinolate content of seed meal derived from transgenic canola hybrids was the same as that from non-transgenic control cultivars.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">Since only the processed oil from transgenic MS8, RF3, or hybrids derived therefrom (MS8 x RF3), are available for human consumption, and the processing removes proteinaceous material, there were no additional toxicity or allergenicity concerns regarding this product. This was further assessed by searching for amino acid sequence homologies with known protein toxins and allergens, and by examining the physiochemical characteristics of the introduced RNAse (barnase), RNAse inhibitor (barstar), and PAT (<i>bar</i>) proteins.</p>\n\n<p style="text-align: justify;">A comparative analysis using the FASTDB algorithm to search three amino acid sequence databases determined that amino acid sequence for each novel protein did not show significant homology with other proteins present in the databases, with the exception of other related compounds. For example, barnase RNAse was similar to ribonucleases from other bacilliform bacteria and PAT was similar to other phosphinothricin acetyltransferases originating from different organisms. No homologies with potential toxins or allergens were observed.</p>\n\n<p style="text-align: justify;">The RNAse, encoded by the barnase gene, was a small single-domain protein, containing no disulfide bonds, metal-ion cofactors or other non-peptide components. When heated, it unfolded completely into an inactive form.</p>\n\n<p style="text-align: justify;">No toxic or allergic effects were expected from PAT, as acetyltransferases are ubiquitous in nature, do not possess proteolytic or heat stability and are highly substrate specific. PAT has a extremely high substrate specificity for L-PPT and dimethylphosphinothricin (DMPT), and experimental data clearly showed that neither L-PPT&#39;s analog L-glutamic acid, D-PPT, nor any other amino acid can be acetylated by the PAT enzyme.</p>\n', 'Enabled', NULL, '2013-08-29 22:35:13'),
(16, 17, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Maize hybrid DK404SR is a yellow dent type used primarily for animal feeding. However, such field corn may be dry- or wet-milled into various processed maize products, such as fructose maize syrups, starch, oil, grits and flour for human food use. The human food uses of grain from DK404SR maize hybrid are not expected to be different from the uses of unmodified maize hybrids. As such, the dietary exposure of consumers to grain from DK404SR maize hybrids will not be different from that for other commercially available field corn varieties.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Nutritional composition for the modified and unmodified maize was compared. The selection of the DK404SR maize hybrid through somaclonal variation had no meaningful effect on the corn plant nutrient levels. The use of maize products derived from DK404SR maize hybrid would therefore have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The novel trait in DK404SR maize hybrid results from modifications of a single maize enzyme, thus altering the sethoxydim binding site without modifying the metabolic abilities of ACCase enzyme. Potential toxicity of this enzyme was therefore not a concern.</p>\n', 'Enabled', NULL, '2013-08-29 22:09:40'),
(17, 48, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Maize line DLL25 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 include products such as corn syrup and corn oil, bran, grits, meal and flour. Oral exposure of the introduced PAT protein, at very low levels, may occur from ingestion of processed corn products, however a lack of mammalian toxicity and the rapid digestibility of this protein has been well demonstrated. The human food uses of grain from DLL25 were not expected to be different from the uses of non-transgenic field corn varieties. As such, the dietary exposure of people to grain from DLL25 would not be different from that for other commercially available field corn varieties</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Forage and grain from DLL25 maize hybrids were analyzed for nutritional composition and compared to the nutritional composition of non-transgenic versions of the same maize hybrids. Proximate and amino acid analyses were performed. Small differences between DLL25 plants and their non-transgenic counterparts were occasionally observed. However, the nutrient composition of DLL25 maize fell within the range of variability for the relevant nutrients reported for maize. The use of corn products derived from DLL25 was not anticipated to have any significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The low potential for toxicity of the PAT protein expressed in the transgenic maize line DLL25 was investigated by searching for amino acid sequence homology with known toxins, examining its physiochemical properties and by acute oral toxicity testing in rats. A search of the GenBank database did not reveal any homologies between the deduced amino acid sequence of the PAT protein and the sequences of known protein toxins or allergens.<br />\nThe PAT enzyme does not possess proteolytic or heat stability typical of toxic compounds, and does not affect the metabolism of the plant. The PAT enzyme has a very specific enzymatic activity that is highly specific for glufosinate and is not expected to have any effect on metabolic pathways in the plant other than detoxification of glufosinate herbicides.</p>\n\n<p style="text-align: justify;">An acute mouse toxicity study of bacterially-derived PAT protein was performed with no toxicity observed. Results indicated that the acute oral LD50 was estimated to be greater than 2500 mg of PAT/kg body weight. The acute oral toxicity data supported the prediction that the PAT protein was non-toxic to humans, by demonstrating a lack of mammalian toxicity</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The PAT protein does not possess characteristics typical of known protein allergens. In addition to a lack of sequence homology with known allergens, the PAT protein was rapidly degraded by simulated gastric fluids (&lt; 1 min), unlike known protein allergens. Based on these properties, it was concluded that there was little or no potential for allergenicity.</p>\n', 'Enabled', NULL, '2013-08-29 23:08:33'),
(18, 18, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\r\n\r\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. The increased levels of lauric acid in the oil allow its use as a replacement for other lauric acid oils such as coconut and palm kernel oil in products such as confectionery coatings and fillings, margarines, spreads, shortenings and commercial frying oils. The level and composition of laurate produced by lines 23-18-17 and 23-198 was no different from that in common food sources, such as coconuts and palm oil.</p>\r\n\r\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\r\n\r\n<p style="text-align: justify;">The modified fatty acid composition of the oil from transgenic canola lines 23-198 and 23-18-17 does not raise any nutritional concerns regarding the intended use of the subject oil. The analysis of levels of erucic acid and glucosinolates were within acceptable levels for canola quality. Similarly, the quality and quantity of seed protein were as expected. The fatty acid profile of high laurate canola was different from all control varieties, with increased levels of lauric acid (up to 40%) and myristic acid, and lower levels of oleic acid and linoleic acid, and less palmitic acid, less stearic, linoleic, arachidic, gadoleic, and slightly more behenic acid. Nonetheless, the overall lipid content of the seed remained unchanged. The consumption of products formulated with this oil would have no significant impact on the nutritional quality of the food supply in North America and Canada. No statistical differences in crude protein, crude fibre, gross energy content, and amino acids were noted between the processed meal of high laurate and control <i>B. napus</i> cultivars. Based on a maximum of 4% oil in the meal, the meal was expected to have 1.6% laurate and 0.16% myristate. As the use rate of meal in livestock rations ranges from 5-25%, the maximum laurate and myristate in meal would be 0.4% and 0.94% respectively. These levels would have no significant impacts on nutrition or carcass quality. In addition, the presence of the aminoglycoside resistance gene in livestock feed would not compromise the efficacy of added antibiotics. Neomycin activity when mixed with meal from high laurate canola remained stable for a period of 56 days responding in the same manner as the control line. It was determined that canola meal derived from lines 23-18-17 and 23-198 was equivalent to meal from traditional <i>B. napus</i> varieties in terms of nutritional composition and safety.</p>\r\n\r\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\r\n\r\n<p style="text-align: justify;">The low potential for toxicity of the thioesterase (Bay TE) and NPTII enzymes expressed in the transgenic canola lines 23-18-17 and 23-198 was demonstrated by studies on the amino aid sequence homology and characteristics of the proteins. The amino acid sequences of the Bay TE and NPTII enzymes were compared with sequences available in GENBank databases and no significant homology was found with any known sequenced toxins or allergens. Significant homology was found with thioesterases from edible plant species. Studies showed that the introduced Bay TE enzyme was not heat stable and was fully degraded into inactive peptides and amino acids following protease digestion. Two potential glycosylation sites were identified but glycosylation of plastid proteins is not known to occur. Similarly, the NPTII enzyme was found to degrade rapidly in simulated mammalian gastric and intestinal fluids. The NPTII protein was not expected to have toxic properties since: the enzyme catalyses only a very specific reaction using aminoglycosidic antibiotics as a substrate; despite wide usage, there have been no reports of toxicity of the protein in the literature; and enzyme levels are less than 0.0008% of total protein in seeds and leaves, and undetected in meal. Both Bay TE and NPTII enzymes are ubitiquitous in nature and no toxic or allergenic effects have ever been reported.</p>\r\n\r\n<p>&nbsp;</p>\r\n', 'Enabled', NULL, '2013-09-03 13:39:25'),
(19, 22, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Typically, canola oil is used by itself as a salad oil or cooking oil, or blended with other vegetable oils in the manufacture of margarine, shortening, salad oil and cooking oils. Refined edible canola oil consists of purified triglycerides (96-97%) and does not contain any detectable protein, hence no amounts of PAT and NPTII proteins were detected in the refined oil of HCN92 canola. Furthermore processing would destroy the enzymatic activity of the PAT and NPTII protein. As such, there will be no human exposure to these proteins as a result of the consumption of refined oil from line HCN92.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from transgenic HCN92 canola and non-transgenic canola did not reveal any significant differences in the levels crude protein, crude fat, crude fibre, ash and gross energy in either whole seed or processed meal. Compositional analysis of processed canola oil indicated that no statistically significant differences between HCN92 and current commercial canola cultivars for the components analysed including fatty acids, chlorophyll and phytosterol content. Furthermore, the content of glucosinolates and erucic acid in glufosinate tolerant canola HCN92 was identical with that of seed from non-transgenic canola. These results collectively demonstrated that the novel herbicide tolerant genes introduced into HCN92 had no observable secondary effects impacting on composition or nutritional quality. The use of refined oil from line HCN92 was judged to be equivalent to traditional canola varieties and would therefore have no significant impact on the nutritional quality of the U.S. and Canadian food supply.</p>\n\n<p style="text-align: justify;">Canola meal was assessed to determine its safety for use in animal feed. <i>In vivo</i> tests performed on broiler chickens fed canola in their diets confirmed the safety previously established with purified PAT protein. It was also determined that PAT protein represented only 0.005% of protein in finished canola meal and enzyme activity was always destroyed in toasted canola meal. The overall results lead to the conclusion that there were no significant risks to livestock following ingestion of transgenic canola meal from HCN92.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">It was determined that there were no toxicity or allergenicity concerns with HCN92, since refined canola oil is the only product for human consumption and does not contain any detectable amount of protein. The absence of toxicity was further demonstrated by examining the amino aid sequence homology and the characteristics of the novel proteins PAT and NPTII, and acute toxicity study in mice.</p>\n\n<p style="text-align: justify;">The amino acid sequences of both the PAT and NPTII proteins were compared to the amino acid sequences of known protein toxins using the GENBank sequence database. No significant similarities were found. Furthermore, the acute oral toxicity of PAT protein was studied in rats and showed no negative effects.</p>\n', 'Enabled', NULL, '2013-08-29 22:25:37'),
(20, 19, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Typically, canola oil is used by itself as a salad oil or cooking oil, or blended with other vegetable oils in the manufacture of margarine, shortening, salad oil and cooking oils. Refined edible canola oil consists of purified triglycerides (96-97%) and does not contain any detectable protein, hence no amounts of CP4 EPSPS or GOX proteins were detected in the refined oil of GT200 canola. The genetic modification of GT200 canola will not result in any change in the consumption pattern for this product. As the introduced gene products are not detectable in the refined oil produced from transgenic canola, there will be no human exposure to these proteins.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from transgenic GT200 canola and non-transgenic canola did not reveal any significant differences in the levels of crude protein, crude fat, crude fibre, ash and gross energy in either whole seed or processed meal. Raw seeds of GT200 were shown to have the same levels of glucosinolates and erucic acid as commercial canola varieties. Seed protein profiles, amino acid and fatty acid compositions were all within the range of the unmodified counterparts. The consumption of refined oil from GT200 was judged to have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;">Several animal feeding studies were conducted to demonstrate the wholesomeness of glyphosate tolerant canola meal. Canola meal is used only for animal feed and is not considered a human food fraction. The feeding studies were conducted to establish the nutritional adequacy of canola meal for animal feeds and represented a worse case scenario in terms of canola consumption by humans. These studies included a four-week rat study on processed and unprocessed meal, a five-day quail (Northern Bobwhite) study on unprocessed meal, and a ten-week trout study on processed meal. The studies all supported the safety of meal from glyphosate-tolerant canola as a component in animal feed.</p>\n\n<p style="text-align: justify;">The rat feeding study examined six week-old Sprague-Dawley rats (10/sex/group) fed either 0, 5 or 15% w/w ground (unprocessed) and processed (toasted and defatted) glyphosate-tolerant canola (GT200 and GT73) and &#39;Westar&#39; canola meal and a diet control (commercial rodent chow with no added canola meal). The study determined that rats fed on diets with unprocessed glyphosate tolerant canola seed had relative liver and kidney weights 5 - 20% greater compared to the diet controls. However, there were no differences in absolute or relative organ weights between the glyphosate-tolerant canola and parental line groups.</p>\n\n<p style="text-align: justify;">The quail feeding study examined thirty northern bobwhite (<i>Colinus virginianus</i>) chicks fed diets for five days and observed for a further three days. Treatment groups were fed a control diet, glyphosate-tolerant canola (both lines GT200 and GT73) or the parental line &#39;Westar&#39;, where canola was incorporated at a rate of 20% of the total weight of the diet. The study did not find any significant effects on body weight or feed consumption between birds in the control or treatment groups. There were no mortalities or overt signs of toxicity in either treatment or control groups.<br />\nSimilarly a trout feeding study examined triplicate groups of 15 fish rainbow trout (<i>Oncorhynchus mykiss</i>) fed glyphosate tolerant canola meal (both lines GT200 and GT73) at 0, 5, 10, 15 or 20% weight of the dry diet for 10 weeks (<i>i.e.</i>, 45 fish/treatment). There was statistical overlap in weight gain of fish fed each dietary treatment and no differences were detected between glyphosate-tolerant canola diets and controls. Fish fed the glyphosate-tolerant canola did not exhibit any adverse effects.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">It was determined that there were no toxicity or allergenicity concerns with GT200, since refined canola oil is the only product for human consumption and does not contain any detectable amount of protein. The absence of toxicity was further demonstrated by examining the amino aid sequence homology and the characteristics of the novel proteins CP4 EPSPS and GOX.</p>\n\n<p style="text-align: justify;">The amino acid sequences of both the CP4 EPSPS and GOX proteins were compared to the amino acid sequences of known protein toxins. No significant similarities were found other than would be expected given that certain functional domains are generally conserved between proteins.</p>\n\n<p style="text-align: justify;">The novel enzyme CP4 EPSPS is one of many EPSPS proteins that occur in plants, fungi and bacteria. The EPSPS proteins are naturally present in foods derived from plants and microbes and have no history of being toxic or allergenic. Similarly, the <i>gox</i> gene was sourced from a common soil bacterium, which has no history of pathogenicity. The GOX enzyme degrades glyphosate and experiments demonstrated that the enzyme displayed a narrow substrate specificity, and appeared not to have any secondary effects on other plant specific pathways.</p>\n\n<p style="text-align: justify;">The digestibility of both proteins in model digestion systems was done <i>in vitro</i> using simulated gastric fluid and simulated intestinal fluid) as mammalian digestion models. Unlike typical protein toxins and allergens, both the CP4 EPSPS and GOX proteins were rapidly digested.</p>\n', 'Enabled', NULL, '2013-08-29 22:15:56');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(21, 32, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Typically, canola oil is used by itself as a salad oil or cooking oil, or blended with other vegetable oils in the manufacture of margarine, shortening, salad oil and cooking oils. Refined edible canola oil consists of purified triglycerides (96-97%) and does not contain any detectable protein, hence no amounts of PAT were detected in the refined oil of HCN28 canola. Furthermore, processing would destroy the enzymatic activity of the PAT protein. As such, there will be no human exposure to the introduced PAT protein as result of the consumption of refined oil from line HCN28.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional analyses of processed canola oil from HCN28 and current commercial canola cultivars were compared for fatty acids, glucosinolates, chlorophyll and phytosterol content. These comparisons indicated no statistically significant differences for the components analyzed. The use of refined oil from HCN28 would therefore have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;">Because canola meal is used as a livestock feed, additional compositional studies were conducted that demonstrated there were no significant differences in the moisture, oil, protein, crude fibre, ash, phytosterol and gross energy of HCN28, Innovator, and non-transgenic lines Excel, Legend and Cyclone. The <i>pat</i> gene did not result in any secondary effects in the seed composition or gross energy levels between glufosinate tolerant and non-transformed <i>B. napus</i> varieties.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">It was determined that there were no toxicity or allergenicity concerns with HCN28, since refined canola oil is the only product for human consumption and does not contain any detectable amount of protein. The absence of toxicity was further demonstrated by examining the amino aid sequence homology and the characteristics of the PAT protein.<br />\nThe potential toxicity of the PAT protein was evaluated in a 14-day repeated dose feeding study with rats. Subject groups consisting of male and female Wistar rats were fed a diet amended with either 5000 or 50,000 ppm purified PAT protein and monitored for dietary intake, weight gain, and observable adverse effects. There were no clinical signs noted and food consumption and body weights were unaffected by treatment. No treatment-related changes were seen in hematology or urinalysis parameters. Organ weight data, macroscopical and microscopical findings also did not distinguish treated groups from controls. Based on these results, there was no evidence of acute toxicity for the PAT protein.</p>\n\n<p style="text-align: justify;">The potential of the PAT protein expressed in T45 transgenic canola to elicit allergic reactions was evaluated by comparing the nucleotide sequence of the <i>pat</i> gene from <i>S. viridochromogenes</i> with available nucleotide sequences contained within the GENBank database. Significant similarity was judged to be &gt;60% identity for &gt;100 base pairs. Using this criterion, the only significant similarity at the nucleotide sequence level was between the <i>pat</i> gene and a previously characterized PPT acetyltransferase from <i>S. viridochromogenes</i> (70.7% identity in 546 nucleotide overlap) and the analogous <i>bar</i> gene from <i>S. hygroscopicus</i> (65.8% identity in 546 nucleotide overlap). When comparing the deduced amino acid sequence of the PAT protein with other proteins in the database, the only noted significant similarity was with an rRNA methyltransferase also isolated from a Streptomyces species (68.2% identity in 132 amino acid overlap). The results of the GENBank database search failed to identify any homologies with known toxins or allergens that have been sequenced.</p>\n\n<p style="text-align: justify;">Also, unlike known protein toxins and allergens, the PAT protein was extremely susceptible to proteolytic degradation. Crude PAT protein containing extracts from transgenic canola plants were compared with purified PPT-acetyltransferase with respect to acid and/or enzymatic hydrolysis under conditions simulating the mammalian stomach. Samples were incubated at 37&deg;C in stomach fluid from beagle dogs for up to 15 minutes, following which aliquots were removed, adjusted to pH 8.0, and tested for acetyltransferase activity. The enzymatic activity of purified PPT-acetyltransferase was completely lost within 1 minute of exposure to stomach fluid (pH 1.1), and within 10 minutes of exposure to fluid adjusted to pH 4.0. While the acetyltransferase activity of crude extracts from transgenic plants was lost equally quickly at pH 1.1, the rate of inactivation was slower at higher pH values.</p>\n', 'Enabled', NULL, '2013-08-29 22:47:30'),
(22, 26, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Refined edible canola oil does not contain any detectable protein and consists of purified triglycerides (96-97%). As the introduced gene products are not detectable in the refined oil produced from transgenic canola, there will be no human exposure to these proteins based on normal consumption patterns.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from transgenic canola lines MS1 and RF1 and non-transgenic canola did not reveal any significant differences in the levels crude protein, crude fat, crude fibre, ash and gross energy in either whole seed or processed meal. The fatty acid composition of oils extracted from both transgenic and non-transgenic canola was statistically the same and within the normal range for canola oil. The transgenic lines meet the standards for canola oil in Canada of containing less than 2% erucic acid and less than 30 micromoles/g glucosinolates in the oil-free meal. It was determined that the consumption of refined oil from MS1, RF1 or hybrids derived therefrom would have no significant impact on the nutritional quality of the food supply in Canada.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">Since only the processed oil from transgenic MS1, RF1, or hybrids derived therefrom (MS1xRF1), will be available for human consumption and the processing removes proteinaceous material, there are no additional toxicity or allergenicity concerns with this product. This was further demonstrated by examining the amino aid sequence homology and the characteristics of the novel proteins RNAse (<i>barnase</i>), RNAse inhibitor (<i>barstar</i>),PAT (<i>bar</i>) and neomycin phosphotransferase (NPTII).</p>\n\n<p style="text-align: justify;">Comparative analyses with amino acid sequences of known protein toxins and allergens in public domain databases did not reveal any homologies. The only sequence homologies were with other related proteins. For example, <i>barnase</i> encoding RNAse was similar to ribonucleases from other bacilli, PAT was similar to other phosphinothricin acetyltransferases originating from different organisms, and NPTII was found to be similar to other peptides that have a similar function (aminoglycoside 3&#39;-phosphotransferases, kanamycin kinases, streptomycin 3&#39;-kinases. No resemblance with potential toxins or allergens was observed.</p>\n', 'Enabled', NULL, '2013-08-29 22:32:56'),
(23, 65, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Refined edible canola oil does not contain any detectable protein and consists of purified triglycerides (96-97%). As the introduced gene products are not detectable in the refined oil produced from transgenic canola, there will be no human exposure to these proteins based on normal consumption patterns.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from transgenic canola lines MS1 and RF2 and non-transgenic canola did not reveal any significant differences in the levels crude protein, crude fat, crude fibre, ash and gross energy in either whole seed or processed meal. The fatty acid composition of oils extracted from both transgenic and non-transgenic canola was statistically the same and within the normal range for canola oil. The transgenic lines meet the standards for canola oil in Canada of containing less than 2% erucic acid and less than 30 micromoles/g glucosinolates in the oil-free meal. It was determined that the consumption of refined oil from MS1, RF2 or hybrids derived therefrom would have no significant impact on the nutritional quality of the food supply in Canada.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">Since only the processed oil from transgenic MS1, RF2, or hybrids derived therefrom (MS1xRF2), will be available for human consumption and the processing removes proteinaceous material, there are no additional toxicity or allergenicity concerns with this product. This was further demonstrated by examining the amino aid sequence homology and the characteristics of the novel proteins RNAse (<i>barnase</i>), RNAse inhibitor (<i>barstar</i>),PAT (<i>bar</i>) and neomycin phosphotransferase (NPTII).</p>\n\n<p style="text-align: justify;">Comparative analyses with amino acid sequences of known protein toxins and allergens in public domain databases did not reveal any homologies. The only sequence homologies were with other related proteins. For example, <i>barnase</i> encoding RNAse was similar to ribonucleases from other bacilli, PAT was similar to other phosphinothricin acetyltransferases originating from different organisms, and NPTII was found to be similar to other peptides that have a similar function (aminoglycoside 3&#39;-phosphotransferases, kanamycin kinases, streptomycin 3&#39;-kinases. No resemblance with potential toxins or allergens was observed.</p>\n', 'Enabled', NULL, '2013-08-29 23:40:26'),
(24, 21, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification of GTS 40-3-2 soybean will not result in any change in the consumption pattern of soybean products. Consequently, the dietary exposure of consumers in the United States and Canada to GTS 40-3-2 soybean products was anticipated to be the same as for other lines of commercially available soybean. Dietary exposure to EPSPS is not novel in that all plants, bacteria and fungi produce this enzyme and the CP4 EPSPS will be ingested as inactive denatured protein since all soybean-derived human food products are heated prior to consumption.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutritional composition of transgenic GTS 40-3-2 soybean and non-transgenic soybean did not reveal any significant differences in the levels of protein, fat, fibre and starch. A number of these parameters were also measured in glyphosate-treated soybeans with the same results. Comparisons of the amino acid composition of the raw soybeans and the fatty acid profiles of extracted oil from transgenic and control plants did not reveal any significant differences. The anti-nutritive activity in raw soybean meal and flour is caused by soybean trypsin inhibitor, which acts to inhibit normal protein digestion in humans and animals. There was no significant difference in the trypsin inhibitor activity between transgenic GTS 40-3-2 soybeans and non-transgenic control soybeans. Likewise, there were no significant differences in the levels of plant lectins, as determined by hemagglutination assay, or isoflavone glucosides between transgenic and control soybeans. These latter substances, which include genistin and daidzin, can exhibit estrogenic and hypocholesterolemic activities. It was determined that the consumption of refined soybean oil from GTS 40-3-2 would have no significant impact on the nutritional quality of the food supply in the United States and Canada.</p>\n\n<p style="text-align: justify;">A series of animal feeding studies were completed using diets incorporating seed or processed fractions from soybean line GTS 40-3-2. These studies addressed the nutritional equivalence of transgenic soybean when used as animal feed, the safety of any expressed protein or peptide (or any other newly produced constituent), and the potential of any pleiotropic effect caused by the insertion process or site of insertion. The animal feeding studies included two independent four week studies in rats (one with unprocessed and one with processed soybeans), a four week dairy cow study, a six week chicken study, a ten week catfish study and a five day quail study. Animals were fed either unprocessed or processed soybeans (dehulled, defatted, toasted). Included in these studies were control groups fed a non-commercial glyphosate-tolerant soybean (61-67-1) and the non-modified parental soybean line (A5403) from which both glyphosate tolerant events were derived. Results from all groups were compared using conventional statistical methods to detect differences between groups in measured parameters. All three soybean samples tested provided similar growth and feed efficiency for rats, chickens, catfish and quail. The nutritional value or wholesomeness of GTS 40-3-2, even when fed to animals at levels much higher than humans would encounter in the diet, was the same as conventional varieties of soybeans.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The low potential for toxicity of transgenic soybean line GTS 40-3-2 was demonstrated by examining the amino acid sequence homology, acute oral toxicity studies on mice, and the characteristics of the proteins. The amino acid sequence of CP4 EPSPS was determined to be closely related to the sequence of the endogenous soybean EPSPS enzyme. An analysis of the amino acid sequence of the inserted CP4 EPSPS enzyme did not show homologies with known mammalian protein toxins and was not judged to have any potential for human toxicity. Additionally, acute oral toxicity studies with purified CP4 EPSPS did not reveal any deleterious effects when mice were administered a dose of 572 mg/kg body weight, which was approximately 1300-fold greater than the highest anticipated potential consumption of CP4 EPSPS from soybean. Furthermore, EPSPS is an enzyme that is ubiquitous in nature, present in plants, fungi and micro-organisms and therefore would not be expected to be toxic or allergenic.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The CP4 EPSPS protein is extremely unlikely to be an allergen. A search for amino acid sequence similarity between the CP4 EPSPS protein and known allergens revealed no significant amino acid sequence homologies. In addition, the potential for allergenicity was assessed based upon the characteristics of known food allergens (stability to digestion, stability to processing). Unlike known protein allergens, CP4 EPSPS was rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric or intestinal fluids. Overall, the CP4 EPSPS does not possess characteristics typical of known protein allergens.</p>\n', 'Enabled', NULL, '2013-08-29 22:23:08'),
(25, 41, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The transgenic soybean G94-1, G94-19 and G168 sublines are the same as non-modified soybeans with the exception of the fatty acid profile which is quite different from that of traditional soybean oil and more similar to that of other high oleic oils such as olive or canola oil. The genetic modifications resulted in a superior, more heat and oxidatively stable soybean oil due to the reduced levels of the oxidatively unstable polyunsaturated fatty acids. The high oleic soybean oil has improved nutritional and functional properties compared to conventional soybean oil or partially hydrogenated soybean oil and will fit into food applications where a highly stable oil is required, such as in fat frying operations. Studies in the United Kingdom determined that the use of high oleic soybean oil may lower the intake of dietary linoleic acid but concluded that the small decrease in saturated fatty acid was likely to be beneficial, by reducing the risk factor for coronary heart disease. It was further concluded that these results should generally be applicable to the European Community and most other countries.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutritional properties of high oleic soybean sublines G94-1, G94-19 and G168 for total protein, oil, carbohydrate, crude fiber, ash, individual amino acid, phytic acid, trypsin inhibitor, stachyose, raffinose and isoflavone contents, determined that there were no differences in the levels of these components compared to non-transgenic soybeans. High Oleic soybean oil contains approximately 10% saturated fats, greater than 80% oleic acid, and low levels of polyunsaturated fatty acids: approximately 2% linoleic acid and 3.5% linolenic acid. Trace amounts (0.5%) of a linoleic acid 9,15 isomer were also detected, which while absent from non-hydrogenated soybean oil, is present at similar levels in butterfat, and is often found at considerably higher levels (typically 1-3%) in partially hydrogenated vegetable oils. The levels of accumulation of two important seed storage proteins, glycinin and beta-conglycinin, were changed. Glycinin levels increased while beta-conglycinin levels decreased. These differences were not expected to have a negative impact as variation in the levels of the various seed storage proteins were also noted in some commercial soybean lines. Antinutritional factors including trypsin inhibitors, phytic acid and the oligosaccharides raffinose and stachyose normally present in non-modified soybeans were similar to those found in the transgenic sublines G94-1, G94-19 and G168. Glycitein and lectin levels were somewhat elevated in the transgenic soybean sublines versus A2396, but were within the middle range reported in the literature. It was determined that the consumption of refined oil from soybean sublines G94-1, G94-19 and G168 would have no significant impact and may improve the nutritional quality of the food supply in the United States and Canada.</p>\n\n<p style="text-align: justify;">Feeding studies carried out with pigs and chickens demonstrated that processed soybean meal derived from high oleic soybeans was nutritionally equivalent to processed soybean meal derived from the conventional soybeans. It was determined that high oleic soybeans may be used as any other non-modified soybean meal and would be treated as any other commodity soybean meal.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">A complete compositional analysis was performed on the transgenic soybean lines. High oleic soybeans did not differ in composition from the parent line or commodity soybean lines (literature ranges) regarding total fat, protein, fiber and ash, amino acids, minerals and vitamins, anti-nutritional factors (phytic acid, trypsin inhibitor, lectins, raffinose, stachyose) and isoflavones. These results demonstrated that there were no significant quantitative or qualitative differences between transgenic soybean sublines G94-1, G94-19 and G168 and elite soybean lines with regard to all of these components. Since no new proteins were expressed in these novel soybeans and the variation in seed protein was considered to be within the natural range of variation it was concluded that there was no need to carry out a complete toxicological assessment since the high oleic acid soybean lines were, with the exception of high oleic acid content, equivalent to non-modified soybeans.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Allergenicity studies demonstrated that there were no significant quantitative or qualitative differences between the high oleic soybean and non-modified elite soybean. The allergenicity potential was the same for transgenic soybean sublines G94-1, G94-19 and G168 and elite soybean with regard to their allergen content.</p>\n', 'Enabled', NULL, '2013-08-29 22:58:18'),
(26, 60, '<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Samples of hay, forage, seed, hulls, and toasted and non-toasted defatted soy meal from transgenic soybean were subjected to proximate analyses (moisture, crude protein, crude fat, ash, acid detergent fibre, neutral detergent fibre, carbohydrate). As well, seed samples were subjected to fatty acid analysis, amino acid analysis, and analyses of minerals (calcium, phosphorous, and potassium). Except in one case, there were no statistaically significant differences between the values determined for transgenic plant samples and corresponding samples obtained from non-transgenic control plants. Statistical differences were seen in the levels of some amino acids between A2704-12 soybeans and non-transgenic soybean, but that the values were still within the normal range reported by the USDA for soybean.</p>\n\n<p style="text-align: justify;"><b>Toxicology</b></p>\n\n<p style="text-align: justify;">Samples of seed were analyzed for stachyose, raffinose, and phytic acid, and additionally for trypsin inhibitor and lectins in seed. The concentrations of phytoestrogens, such as daidzein, genistein, and glycitein, were determined for samples of seed, and toasted and non-toasted soy meal. The levels of these compounds were not statistically different between samples from non-transgenic and transgenic soybeans.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The low potential for allergenicity of the PAT protein has previously been established through amino acid sequence comparisons with known protein allergens and digestability studies using simulated gastric and intestinal fluids. Additionally, soybean seed extracts from line A2704-12 and from non-transgenic control plants were screened against a panel of sera from 16 soy-allergic individuals using the radioallergosorbent test (RAST). The results of this study did not reveal any qualitative or quantitative difference in endogenous soybean allergen content between transgenic and non-transgenic soybean.</p>\n', 'Enabled', NULL, '2013-08-29 23:34:15'),
(27, 40, '<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Samples of have, forage, seed, hulls, and toasted and non-toasted defatted soy meal from transgenic soybean were subjected to proximate analyses (moisture, crude protein, crude fat, ash, acid detergent fibre, neutral detergent fibre, carbohydrate). As well, seed samples were subjected to fatty acid analysis, amino acid analysis, and analyses of minerals (calcium, phosphorous, and potassium). In all cases, there were no statistaically significant differences between the values determined for transgenic plant samples and corresponding samples obtained from non-transgenic control plants.</p>\n\n<p style="text-align: justify;"><b>Toxicology</b></p>\n\n<p style="text-align: justify;">Samples of seed were analyzed for stachyose, raffinose, and phytic acid, and additionally for trypsin inhibitor and lectins in seed. The concentrations of phytoestrogens, such as daidzein, genistein, and glycitein, were determined for samples of seed, and toasted and non-toasted soy meal. The levels of these compounds were not statistically different between samples from non-transgenic and transgenic soybeans.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The low potential for allergenicity of the PAT protein has previously been established through amino acid sequence comparisons with known protein allergens and digestability studies using simulated gastric and intestinal fluids. Additionally, soybean seed extracts from line A5547-127 and from non-transgenic control plants were screened against a panel of sera from 16 soy-allergic individuals using the radioallergosorbent test (RAST). The results of this study did not reveal any qualitative or quantitative difference in endogenous soybean allergen content between transgenic and non-transgenic soybean.</p>\n', 'Enabled', NULL, '2013-08-29 22:56:21'),
(28, 39, '<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Samples of hay, forage, seed, hulls, and toasted and non-toasted defatted soy meal from transgenic soybean were subjected to proximate analyses (moisture, crude protein, crude fat, ash, acid detergent fibre, neutral detergent fibre, carbohydrate). As well, seed samples were subjected to fatty acid analysis, amino acid analysis, and analyses of minerals (calcium, phosphorous, and potassium). The values for each of these parameters was found to be within the normal range reported by the USDA for soybean.</p>\n\n<p style="text-align: justify;"><b>Toxicology</b></p>\n\n<p style="text-align: justify;">Samples of seed were analyzed for stachyose, raffinose, and phytic acid, and additionally for trypsin inhibitor and lectins in seed. The concentrations of phytoestrogens, such as daidzein, genistein, and glycitein, were determined for samples of seed, and toasted and non-toasted soy meal. The levels of these compounds were not statistically different between samples from non-transgenic and transgenic soybeans.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The low potential for allergenicity of the PAT protein has previously been established through amino acid sequence comparisons with known protein allergens and digestability studies using simulated gastric and intestinal fluids.</p>\n', 'Enabled', NULL, '2013-08-29 22:55:00'),
(29, 53, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Potatoes are considered to be a staple food, constituting up to 37% of the total average vegetable intake. The new trait introduced into these transgenic potatoes was not expected to result in any change in the consumption pattern for potatoes. The occurrence of PLRV, including the replicase protein component, is ubiquitous in the agricultural environment and commonly occurs in the tubers of conventional potato plants. The use of replicase protein of PLRV and the genetic material necessary for its production was therefore determined not to pose a dietary risk under normal conditions. Due to their protection from CPB damage and resistance to infection by PLRV, these potato lines are expected to replace some existing commercial potato cultivars in all potato product applications. Hence, they will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of macro- and micronutrients from these bioengineered lines revealed only small differences with the respective values from non-transgenic controls and in each case the level was within the normal range of variation reported for commercial potatoes.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The glycoalkaloids, solanine and chaconine, are naturally occurring toxicants found in potato tubers, particularly in green tubers that have been exposed to sunlight. The concentration of total glycoalkaloids (TGA) in transgenic tubers ranged between 4.3-17.1 mg/100g fresh weight tissue, with a mean value of 6.7 mg/100g fresh weight tissue. This was comparable to the TGA range of 2.5-16.1 mg/100g fresh weight tissue, previously measured in tubers from commercial non-transgenic cultivars of Atlantic, Gemchip, Norchip and Russet Burbank. In each case, the TGA concentration in transgenic tubers was below the administrative guideline of 20 mg/100g fresh weight that has previously been established for TGA in potato. The toxicity of the Cry3A, and NPTII proteins was previously assessed, using toxicity testing in mice, with no adverse findings. Furthermore, the amino acid sequence of the Cry3A protein expressed in these potato lines is closely related to the sequence of the same protein that is present in strains of <i>B. thuringiensis</i> that have been used for over 30 years as commercial organic microbial insecticides. Toxicity testing was not considered necessary for the PLRV replicase because of the long history of exposure of human beings to this protein through the consumption of PLRV-infected potatoes. An analysis of the amino acid sequences of the inserted Cry3A protein and PLRV replicase did not show homologies with known mammalian protein toxins and they are not judged to have any potential for human toxicity. Based on the evidence presented, it was concluded that all four novel proteins were non-toxic to humans.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The Cry3A protein and PLRV replicase do not possess characteristics typical of known protein allergens. There were no regions of homology when the sequences of these introduced proteins were compared to the amino acid sequences of known protein allergens. Unlike known protein allergens, the Cry3A protein was rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric or intestinal fluids. It was determined that these two proteins were highly unlikely to be allergenic.</p>\n', 'Enabled', NULL, '2013-08-29 23:24:08'),
(30, 20, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Potatoes are considered to be a staple food, constituting up to 37% of the total average vegetable intake. The genetic modification present in the BT06, BT10, BT12, BT16, BT17, BT18 and BT23 transgenic lines will not result in any change in the consumption pattern for potatoes. Due to their protection from CPB damage, the CPB-resistant potato lines may replace some existing commercial potato cultivars in all potato product applications. Hence, they will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The major components of CPB-resistant potato lines were analyzed for nutritional constituents, proximate composition (protein, fat, ash, total dietary fiber, carbohydrate, and calories), internal quality characteristics (hollow heart and brown center, internal brown spots, vascular discoloration, and blackspot bruise), and French fry quality characteristics and compared with those of Russet Burbank tubers. The analysis of nutrients from each of the seven transgenic potato lines and non-transgenic potato did not reveal any significant differences in the levels of crude protein, ash, and starch. Similarly, the levels of micronutrients and trace elements, including thiamine, niacin, riboflavin, vitamin C, calcium, iron and zinc, were comparable to those of unmodified Russet Burbank. There were significant differences in carbohydrate, fat and fibre although in each case the measured concentration was within the range normally reported for potatoes. It was concluded that the consumption of products from CPB-resistant potatoes has no significant impact on the nutritional quality of the Canadian and American food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The glycoalkaloids, solanine and chaconine, are naturally occurring toxicants found in potato tubers, particularly green tubers that have been exposed to sunlight. Analyses of total glycoalkaloid (TGA) levels in each of the transgenic lines demonstrated that in each case the level was below the administrative guideline of 20 mg/100g fresh weight that has previously been established for TGA in potato. Line BT17 was found to have significantly higher glycoalkaloid levels (pThe amino acid sequence of the Cry3A protein expressed in CPB-resistant potato lines is closely related to the sequence of the same proteins that are present in strains of <i>B. thuringiensis</i> that have been used for over 30 years as commercial organic microbial insecticides. An analysis of the amino acid sequence of the inserted Cry3A protein did not show homologies with known mammalian protein toxins and was not judged to have any potential for human toxicity. Additionally, acute oral toxicity studies with purified Cry3A protein did not reveal any deleterious effects when mice were administered a dose of 5220 mg/kg body weight.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The likelihood of the Cry3A and NPTII 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.</p>\n\n<p style="text-align: justify;">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, and glycosylation. The Cry3A and NPTII proteins did not demonstrate any characteristics normally associated with food allergens. Unlike known protein allergens, which are normally resistant to digestion, the Cry3A and NPTII proteins were rapidly inactivated and degraded when subjected to typical mammalian acidic stomach conditions, <i>i.e.</i> in simulated gastric fluids.</p>\n', 'Enabled', NULL, '2013-08-29 22:18:58'),
(31, 54, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Potatoes are considered to be a staple food constituting up to 37% of the total average vegetable intake. The genetic modification present in transgenic potato lines RBMT15-101, SEMT15&ndash;02 and SEMT15&ndash;15 will not result in any change in the consumption pattern for potatoes. Due to their protection from CPB damage resistance and to infection by PVY, these potato lines may replace some existing commercial potato cultivars in all potato product applications. Hence, they will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of macro- and micronutrients from transgenic potato lines revealed only small differences with the respective values from non-transgenic controls and in each case the level was within the normal range of variation reported for commercial potatoes. It was concluded that the consumption of products from CPB-resistant potatoes has no significant impact on the nutritional quality of the Canadian and American food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The glycoalkaloids, solanine and chaconine, are naturally occurring toxicants found in potato tubers, particularly in green tubers that have been exposed to sunlight. Analyses of total glycoalkaloid (TGA) levels in each of the transgenic lines demonstrated that in each case the level was below the administrative guideline of 20 mg/100g fresh weight that has previously been established for TGA in potato.</p>\n\n<p style="text-align: justify;">The amino acid sequence of the Cry3A protein expressed in these potatoes is closely related to the sequence of the same proteins that are present in strains of <i>B. thuringiensis</i> that have been used for over 30 years as commercial organic microbial insecticides. An analysis of the amino acid sequences of the inserted Cry3A and PVY CP did not show homologies with known mammalian protein toxins and they were not judged to have any potential for human toxicity. The history of known safe consumption of PVY CP from virus-infected plant products provides additional evidence of lack of toxicity.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The Cry3A protein and PVY CP do not possess characteristics typical of known protein allergens. There were no regions of homology when the deduced amino acid sequences of these introduced proteins were compared to the amino acid sequences of known protein allergens. Unlike known protein allergens, the Cry3A protein was rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric or intestinal fluids. The Cry3A protein and PVY CP are extremely unlikely to be allergenic.</p>\n', 'Enabled', NULL, '2013-08-29 23:26:44'),
(32, 10, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Potatoes are considered to be a staple food in North America, constituting up to 37% of the total average vegetable intake. The genetic modification present in the ATBT04-6, ATBT04-27, ATBT04-30, ATBT04-31, ATBT04-36, SPBT02-5 and SPBT02-7 transgenic lines will not result in any change in the consumption pattern for potatoes. Due to their protection from CPB damage, the NewLeaf&trade; Atlantic and Superior cultivars are expected to replace some existing commercial potato cultivars in all potato product applications. Hence, they will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The major components of CPB-resistant potato lines were analyzed for nutritional constituents, proximate composition (protein, fat, ash, total dietary fiber, carbohydrate, and calories), internal quality characteristics (hollow heart and brown center, internal brown spots, vascular discoloration, and blackspot bruise), and French fry quality characteristics and compared with those of non-transgenic &lsquo;Atlantic&rsquo; and &lsquo;Superior&rsquo; tubers. The analysis of nutrients from each of these transgenic potato lines and from non-transgenic potato did not reveal any significant differences in levels of crude protein, ash, or starch. Similarly, the levels of micronutrients and trace elements, including thiamine, niacin, riboflavin, vitamin C, calcium, iron and zinc, were comparable to those of unmodified counterpart potatoes. It was concluded that the consumption of products from CPB-resistant potatoes has no significant impact on the nutritional quality of the Canadian and American food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The glycoalkaloids, solanine and chaconine, are naturally occurring toxicants found in potato tubers, particularly in green tubers that have been exposed to sunlight. Analyses of total glycoalkaloid (TGA) levels in each of the transgenic lines demonstrated that in each case the level was below the administrative guideline of 20 mg/100g fresh weight that has previously been established for TGA in potato.</p>\n\n<p style="text-align: justify;">The amino acid sequence of the Cry3A protein expressed in CPB-resistant potato lines is closely related to the sequence of the same proteins that are present in strains of <i>B. thuringiensis</i> that have been used for over 30 years as commercial organic microbial insecticides. An analysis of the amino acid sequence of the inserted Cry3A protein did not show homologies with known mammalian protein toxins and was not judged to have any potential for human toxicity.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The likelihood of the Cry3A and NPTII 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.</p>\n\n<p style="text-align: justify;">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, and glycosylation. The Cry3A and NPTII proteins did not demonstrate any characteristics normally associated with food allergens. Unlike known protein allergens, which are normally resistant to digestion, the Cry3A and NPTII proteins were rapidly inactivated and degraded when subjected to typical mammalian acidic stomach conditions, i.e. in simulated gastric fluids.</p>\n', 'Enabled', NULL, '2013-08-29 21:53:55'),
(33, 14, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Refined cottonseed oil and cellulose from processed linters of cottonseed are the only cotton products consumed by humans. Processed linters are essentially pure cellulose (&gt;99%) and are subjected to heat and solvent treatment that would be expected to remove and destroy DNA and protein. Similarly, the refining process for cottonseed oil includes heat, solvent and alkali treatments that would remove and destroy DNA and protein. Typically, cottonseed oils are pooled and blended together and it is anticipated that the oil from 531, 757, and 1076 cottonseed will not be handled or treated any differently than other cottonseed oils. The genetic modification in these cotton lines will not result in any change in the consumption pattern for this product. As the introduced gene products are not detectable in the refined oil produced from transgenic cotton, there is no anticipated human exposure to these proteins based on normal consumption patterns.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional comparison of cottonseed from lines 531, 757 and 1076 was made to commercial non-transgenic cottonseed. The cottonseed used for compositional analyses was taken from four to six trial sites. The compositional analyses of cottonseed included proximates (crude protein, crude fat, crude fibre, ash and gross energy), amino acid composition, fatty acids profile, aflatoxins and levels of tocopherols.</p>\n\n<p style="text-align: justify;">The concentrations of protein, oil, carbohydrate and ash were the same for transgenic cotton lines 531, 757 and 1076 and the control parent line Coker 312 line. Line 1076 contained slightly higher carbohydrate and slightly lower oil concentrations than the control line, but both were within the normal range for cottonseed. Fatty acid concentration was within the normal published range for cottonseed. Additional analyses of composite samples of cottonseed products (raw meal, toasted meal, kernel, refined oil) from each line showed that the products from the transgenic cotton lines were similar in composition to the control line. Feed studies of a four week rat feeding trial showed no difference in weight gain of animals fed diets containing 10% raw cottonseed meal from line 531 vs. Coker 312.<br />\nThe analysis of the fatty acid composition of refined oil from 531 and 757 cotton did not reveal any significant differences with the parent, non-transgenic variety and was within the normal range reported for cottonseed oils. In addition, the levels of alpha-tocopherol in refined oil from transgenic and control lines were similar. The consumption of refined oil from 531 and 757 cottonseed will have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Toxicity of cotton lines was assessed by analysis of naturally occurring toxins in cotton and an evaluation of the novel proteins Cry1Ac and NPTII. Toxicant analyses in cottonseed and refined oil evaluated levels of gossypol and cyclopropenoid fatty acids (sterculic and malvalic acid).</p>\n\n<p style="text-align: justify;">Cotton is known for the production of anti-nutritional factors and untreated raw seed is unsuitable as livestock feed for monogastric animals. The transgenic and parental lines were assayed for the presence of potential toxins, including gossypol, dihydrosterculic acid, sterculic acid, malvalic acid and aflatoxins B1, B2, G1 and G2. At detection thresholds of 0.002% or 1 ppb, respectively, neither free gossypol nor any of the four aflatoxins were detected in the oil from transgenic cottonseed. Similarly, the respective levels of the cyclopropenoid fatty acids (dihydrosterculic, sterculic and malvalic) were statistically identical in cottonseed samples from transgenic and control lines.<br />\nThe deduced amino acid sequences of both Cry1Ac and NPTII were compared to the amino acid sequence of known protein toxins. No significant similarities were found.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Refined cottonseed oil and cellulose from linters are devoid of detectable protein and their consumption is unlikely to result in an allergic reaction since most allergens are proteins. Therefore the potential for cottonseed oil or linters from transgenic cotton lines to constitute a source of allergens is extremely low.<br />\nThe Cry1Ac and NPTII proteins are not likely to be toxic or allergenic. The potential for allergenicity was assessed based on studies that included digestive degradation and sequence similarity to known allergens. The plant expressed proteins Cry1Ac and NPTII showed no significant protein sequence homology to a database of known toxins or allergens. Also, unlike known allergenic proteins, both Cry1Ac and NPTII were rapidly degraded when exposed to simulated gastric fluids (pH 1.2, pepsin digestion).</p>\n', 'Enabled', NULL, '2013-08-29 22:03:18');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(34, 52, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. Processed linters are essentially pure cellulose (&gt;99%) and are subjected to heat and solvent treatment that would be expected to remove and destroy DNA. CP4 EPSPS was detected in combed lint but not in brown linter stock, the first product in the sequence of processing linters for cellulose. It is generally accepted that the refined oil does not contain protein. The refining process for cottonseed oil includes heat, solvent and alkali treatments that remove and destroy DNA and protein. Although refined cottonseed oil from these lines was not tested for the presence of CP4 EPSPS or NPTII protein, other data were presented confirming that proteins are generally not detectable in such oil at a sensitivity of 1.3 ppm. It was concluded that there would be no dietary exposure to the novel proteins expressed in cotton line 1445.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional comparison of cottonseed oil from line 1445 was made to commercial non-transgenic cottonseed oil. The cottonseed used for compositional analyses was taken from six trial sites during two growing seasons. The compositional analyses of cottonseed components measured included proximates (protein, fat, ash, carbohydrates, moisture, crude fibre), amino acid composition, fatty acids profile, and levels of tocopherols.</p>\n\n<p style="text-align: justify;">Some minor differences in proximate analysis between the control, the modified line and the treated modified line (pThe composition of the oil from cotton line 1445 was comparable to that for cottonseed oil from the control line Coker 312 and components were within the normal range reported for cottonseed oil. Based on these data it was determined that refined oil and processed linters derived from glyphosate-tolerant cotton line 1445 were nutritionally and compositionally comparable to that from conventional cotton and were not considered to pose a risk to human health and safety.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Toxicity of cotton lines was assessed by analysis of naturally occurring toxins in cotton and an evaluation of the novel proteins CP4 EPSPS and NPTII. Toxicant analyses in cottonseed and refined oil evaluated levels of gossypol and cyclopropenoid fatty acids (sterculic and malvalic acid).</p>\n\n<p style="text-align: justify;">Cottonseed contains a high number of anti-nutritional factors and the raw seed is unsuitable for monogastric animals. Gossypol has numerous toxic effects on mammals, including heart damage and heart failure, such that whole cottonseed or cottonseed meal is not used in human foods and the presence of gossypol limits its use as in animal feed. However, removal or inactivation of gossypol during processing enables the use of some cottonseed meal in feed for fish, poultry and pigs.</p>\n\n<p style="text-align: justify;">The gossypol content was higher in the transformed line compared to the control parent line Coker 312, but still within the range found for field-grown cotton. Gossypol was below the level of detection in cottonseed oil from both the transformed lines and the control.</p>\n\n<p style="text-align: justify;">The cyclopropenoid fatty acids, sterculic acid (C-17), dihydrosterculic acid (C-19) and malvalic acid (C-18), are unique fatty acids common in cotton and produce undesirable biological effects. These include the inhibition of biodesaturation of stearic to oleic acid, affecting phospholipid biosynthesis. There were no statistical differences detected in the content of these fatty acids in cottonseed from the control parent line Coker 312 and from line 1445 with or without glyphosate treatment. In refined oil (single samples processed from cottonseed pooled from the six field sites) the levels of dihydrosterculic and malvalic acids were virtually identical in line 1445 and the control line Coker 312. The level of sterculic acid was slightly higher but within the range for cotton.</p>\n\n<p style="text-align: justify;">Anthocyanin, flavonoid and tannin in the transformed lines were within acceptable levels for cotton and within the range of the controls.</p>\n\n<p style="text-align: justify;">The toxicity of the CP4 EPSPS was previously tested by acute gavage exposure in mice and no deleterious effects were observed. The CP4 EPSPS protein was administered at levels 1000 fold to those anticipated in consumption of food products (high dose: 572 mg/kg body weight). A similar toxicity study on NPTII protein was performed and no deleterious effects were observed. The NPTII protein was administered in three cumulative target dosages of up to 5000 mg/kg body weight. Clinical observations in both studies detected no abnormalities and it was concluded that the toxicity of the two novel proteins was low.</p>\n\n<p style="text-align: justify;">The deduced amino acid sequences of both CP4 EPSPS and NPTII were compared to the amino acid sequence of known protein toxins. No significant similarities were found.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The CP4 EPSPS and NPTII proteins are not likely to be toxic or allergenic. The potential for allergenicity was assessed based upon characteristics such as glycosylation, resistance to heat and digestive degradation, and sequence similarity to known allergens.</p>\n\n<p style="text-align: justify;">Refined cottonseed oil and cellulose from linters are devoid of protein and, given that most allergens are proteins, their consumption is unlikely to result in an allergic reaction. Therefore the potential for cottonseed oil or linters from cotton line 1445 to constitute a source of allergens is extremely low. Furthermore EPSPS proteins are naturally present in foods derived from plants and microbes and have no history of being allergenic. Both CP4 EPSPS and NPTII proteins are widespread in nature and no toxic or allergenic effects have ever been reported.</p>\n\n<p style="text-align: justify;">The deduced amino acid sequences of CP4 EPSPS and NPTII showed no homologies with sequences of known toxins or allergens assembled from the Swissprot, Genepept, and PIR protein databases. Unlike known allergens that are resistant to digestion, previous studies demonstrated that the CP4 EPSPS and NPTII proteins were rapidly degraded in a simulated digestive system and inactivated by heat treatment. Data presented showed that the CP4 EPSPS enzyme was rapidly inactivated by heat and by digestion in simulated mammalian gastric fluid. Similarly, NPTII was shown to be rapidly degraded under simulated mammalian digestive conditions, being completely removed after 10 seconds in simulated gastric fluid and with 50% digested after five minutes in simulated intestinal fluid.</p>\n\n<p style="text-align: justify;">The CP4 EPSPS protein sequence does not contain typical glycosylation sequences and comparisons between CP4 EPSPS protein in crude extracts from cottonseed of line 1445 did not differ from purified CP4 EPSPS, supporting the conclusion that the CP4 EPSPS was not glycosylated.</p>\n\n<p style="text-align: justify;"><b>Residue Assessment</b></p>\n\n<p style="text-align: justify;">The metabolism of glyphosate has been investigated in several varieties of plants, the metabolic pathway in tolerant crops being the same as in non-tolerant crops. In tolerant plants containing the enzyme CP4 EPSPS, like cotton line 1445, glyphosate is only slowly metabolized to AMPA (aminomethylphosphonic acid) as in non-tolerant crops. No detectable residues would occur in cottonseed oil.</p>\n\n<p style="text-align: justify;">Studies with livestock animals also show that glyphosate and AMPA are not metabolized, or are only insignificantly metabolized. Therefore, residues would not be present in meat, milk and eggs of animals fed with tolerant or non-tolerant crops treated with the herbicide glyphosate.</p>\n', 'Enabled', NULL, '2013-08-29 23:16:58'),
(35, 34, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. Processed linters are essentially pure cellulose (&gt;99%) and are subjected to heat and solvent treatment that would be expected to remove and destroy DNA. It is generally accepted that the refined oil does not contain protein. The refining process for cottonseed oil includes heat, solvent and alkali treatments that remove and destroy DNA and protein. The refined cottonseed oil from these lines was tested for the presence of Cry1Ac, nitrilase and NPTII, which were undetectable at a detection limit of 0.01 ppm. It was concluded that there would be no dietary exposure to the novel proteins expressed in these cotton lines.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional comparisons of cottonseed oil, cottonseed and meal from lines 31808 and 31807 were made to the same materials from commercial non-transgenic cotton. Parameters measured included proximate analysis (moisture, crude fat/oil, protein, and ash) of cottonseed meal; fibre analysis (crude fibre, acid detergent, and neutral detergent fibres) of cottonseed; fatty acid composition of refined cottonseed oil; and amino acid profile of cottonseed meal. No significant differences between the transgenic lines and the traditionally bred lines were observed for any of these parameters.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Cottonseed contains a high number of anti-nutritional factors and the raw seed is unsuitable for monogastric animals. Gossypol has numerous toxic effects on mammals, including heart damage and heart failure, such that whole cottonseed or cottonseed meal is not used in human foods and the presence of gossypol limits its use in animal feed. However, removal or inactivation of gossypol during processing enables the use of some cottonseed meal in feed for fish, poultry and pigs.</p>\n\n<p style="text-align: justify;">The cyclopropenoid fatty acids, sterculic acid (C-17), dihydrosterculic acid (C-19) and malvalic acid (C-18), are unique fatty acids common in cotton and produce undesirable biological effects, including the inhibition of biodesaturation of stearic to oleic acid, affecting phospholipid biosynthesis.</p>\n\n<p style="text-align: justify;">The levels of gossypol and cyclopropenoid fatty acids in transgenic cotton lines were measured and found to be within the normal range of variation reported for traditionally bred cotton cultivars.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Refined cottonseed oil and cellulose from linters are devoid of protein and, given that most allergens are proteins, their consumption is unlikely to result in an allergic reaction. Therefore the potential for cottonseed oil or linters from cotton lines 31807 and 31808 to constitute a source of allergens is extremely low.</p>\n', 'Enabled', NULL, '2013-08-29 22:50:58'),
(36, 29, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. Processed linters are essentially pure cellulose (&gt;99%) and are subjected to heat and solvent treatment that would be expected to remove and destroy DNA. It is generally accepted that the refined oil does not contain protein. The refining process for cottonseed oil includes heat, solvent and alkali treatments remove and destroy DNA and protein. The refined cottonseed oil from these lines was tested for the presence of nitrilase and NPTII, which were undetectable. It was concluded that there would be no dietary exposure to the novel proteins expressed in these cotton lines.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional comparison of cottonseed oil, cottonseed and meal from BXN&trade; cotton was made to the same materials from commercial non-transgenic cotton. Parameters measured included proximate analysis (moisture, crude fat/oil, protein, and ash) of cottonseed meal; fibre analysis (crude fibre, acid detergent, and neutral detergent fibres) of cottonseed; fatty acid composition of refined cottonseed oil; and amino acid profiles of cottonseed meal. No significant differences between the transgenic lines and the traditionally bred lines were observed for any of these parameters.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Cottonseed contains a high number of anti-nutritional factors and the raw seed is unsuitable for monogastric animals. Gossypol has numerous toxic effects on mammals, including heart damage and heart failure, such that whole cottonseed or cottonseed meal is not used in human foods and the presence of gossypol limits its use in animal feed. However, removal or inactivation of gossypol during processing enables the use of some cottonseed meal in feed for fish, poultry and pigs.</p>\n\n<p style="text-align: justify;">The cyclopropenoid fatty acids, sterculic acid (C-17), dihydrosterculic acid (C-19) and malvalic acid (C-18), are unique fatty acids common in cotton and produce undesirable biological effects, including the inhibition of biodesaturation of stearic to oleic acid, affecting phospholipid biosynthesis.</p>\n\n<p style="text-align: justify;">The levels of gossypol and cyclopropenoid fatty acids in the transgenic cotton line were measured and found to be within the normal range of variation reported for traditionally bred cotton cultivars.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Refined cottonseed oil and cellulose from linters are devoid of protein and, given that most allergens are proteins, their consumption is unlikely to result in an allergic reaction. Therefore the potential for cottonseed oil or linters from BXN&trade; cotton to constitute a source of allergens is extremely low. In addition, the enzyme nitrilase does not have the properties of known allergens, such as glycosylation, protease stability, and presence in food at high concentrations. Also, an amino acid sequence homology search against public domain databases did not reveal any homologies between known protein allergens or toxins and the nitrilase enzyme.</p>\n', 'Enabled', NULL, '2013-08-29 22:39:19'),
(37, 61, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of the FLAVR SAVR&trade; tomato will be as both fresh and processed tomato products. Fresh market tomatoes are eaten whole and sliced or diced in a variety of foods. Processed tomatoes are consumed in the form of soups, preserves, ketchup, paste and prepared sauces. The genetic modification of these novel tomatoes will not result in any change in the consumption pattern for fresh or processed tomato products. The transgenic FLAVR SAVR&trade; lines are expected to replace other tomato cultivars currently in use due to improved quality and handling characteristics. Hence, it will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from the novel FLAVR SAVR&trade; tomatoes and non-transgenic control lines did not reveal any significant differences in the levels of macro- and micronutrients, pH, total acidity, total solids, and sugars. The consumption of this product will, therefore, have no significant impact on the nutritional quality of the food supply in Canada and the United States.</p>\n\n<p style="text-align: justify;">The presence of NPTII protein has been judged to be insignificant with respect to any human health risk due to exposure.</p>\n\n<p style="text-align: justify;">Alpha-tomatine is the principal naturally occurring glycoalkaloid in tomato, and the level of alpha-tomatine decreases as the fruit matures, so that the amounts in vine-ripened red tomatoes are negligible. Solanine and chaconine, which are the main glycoalkaloids occurring in potato, have been found in tomato in lesser amounts. A comparison of the amounts of alpha-tomatine in transgenic and non-transgenic tomatoes did not reveal any statistically significant difference and the levels were within the normal range reported for tomatoes. Alpha-tomatine was detected (at a limit of detection of 2.5 ppm) in only one out of 38 red ripe FLAVR SAVR&trade; fruits and four out of 60 red ripe commercial tomato fruits. Other than reduced polygalacturonase activity, the disease, pest and other agronomic characteristics of the FLAVR SAVR&trade; tomato were comparable to unmodified varieties.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The reduced synthesis of native PG was not judged to have any potential for human toxicity or allergenicity. Analysis of biochemical components of FLAVR SAVR&trade; tomatoes were compared to nontransgenic tomatoes and no toxic components were identified in concentrations that differed significantly from the concentrations in nontransgenic tomatoes. The antisense PG gene did not encode for any new protein products and therefore, should not have any toxic properties. The novel protein NPTII expressed by the <i>neo</i> gene is widespread in nature and no toxic or allergenic effects have ever been reported.</p>\n\n<p style="text-align: justify;">Additional data from three 28-day rat feeding trials demonstrated no biologically significant changes in body weight, organ weight, food consumption, hematologic parameters, and clinical chemistry findings. There was disparity among the three studies regarding the incidence of rats with gastric erosions. Although no definitive conclusions could be drawn regarding the etiology(ies) of these erosions, it was determined that they were also present in rats fed non-transgenic tomatoes and that, where they occurred, they were no more severe in rats fed FLAVR SAVR&trade; tomatoes than in rats fed non-transgenic tomatoes.</p>\n', 'Enabled', NULL, '2013-08-29 23:36:00'),
(38, 43, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\r\n\r\n<p style="text-align: justify;">The human consumption of the modified tomato line 1345-5 will be as both fresh and processed tomato products. Fresh market tomatoes are eaten whole and sliced or diced in a variety of foods. Processed tomatoes are consumed in the form of soups, preserves, ketchup, paste and prepared sauces. The genetic modification of these novel hybrids will not result in any change in the consumption pattern for fresh or processed tomato products. Line 1345-4 is expected to replace other tomato cultivars currently in use due to improved quality and handling characteristics. Hence, it will provide an alternate or additional choice to consumers and food manufacturers.</p>\r\n\r\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\r\n\r\n<p style="text-align: justify;">The analysis of nutrients from the novel 1345-4 line and the non-transgenic 91103-114 parental line did not reveal any significant differences in the levels of macro- and micronutrients. The presence of NPTII protein was judged to be insignificant with respect to any human health risk due to exposure. The consumption of this product will, therefore, have no significant impact on the nutritional quality of the food supply in Canada and the United States. Tomatoes produce naturally occurring glycoalkaloids, alpha-tomatine being the most common. The level of alpha-tomatine decreases as the fruit matures, so that the amounts in vine-ripened red tomatoes are negligible. The concentration of alpha-tomatine in immature tomatoes from transgenic line 1345-4 was 1.13-1.37 mg/100g fresh weight tissue, as compared with 3.37-3.59 mg/100g fresh weight tissue for the unmodified 91103- 114 parental line. However, these levels evened out once the fruit ripened into mature red tomatoes. In vine-ripened red tomatoes, the amount of alpha-tomatine in transgenic tomatoes was 0.11/100g fresh weight tissue compared to 0.07 mg/100g fresh weight tissue in the non-transgenic parental line. Other than reduced ACC synthase activity, the disease, pest and other agronomic characteristics of the transgenic 1345-4 line were comparable to the unmodified parental line.</p>\r\n\r\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\r\n\r\n<p style="text-align: justify;">The reduced synthesis of native ACC synthase was judged not to have any potential for additional human toxicity or allergenicity. The truncated ACC synthase gene was not expressed in line 1345-4 and should not have any toxic or allergenic properties. The NPTII protein is widespread in nature and no toxic or allergenic effects have ever been reported.</p>\r\n', 'Enabled', NULL, '2013-11-18 17:26:26'),
(40, 59, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of the 1401F, H282F, 11013F and 7913F hybrids will be mainly as processed tomato product in the form of soups, preserves, ketchup, paste and prepared sauces. The genetic modification of these novel hybrids will not result in any change in the consumption pattern for processed tomato products. The novel hybrids are expected to replace other tomato cultivars currently in use due to improved quality and handling characteristics. Hence, they will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The analysis of nutrients from the novel 1401F hybrid line and the non-transgenic 1401 hybrid did not reveal any significant differences in the levels of macro- and micronutrients in either fresh tomatoes or processed tomato paste. The consumption of this product will, therefore, have no significant impact on the nutritional quality of the food supply in Canada and the United States.</p>\n\n<p style="text-align: justify;">An extensive analysis of fresh fruit and tomato paste samples derived from tomato line F was made and results compared to the range of values produced by non-modified, commercial tomato varieties. Results for the bulk components (soluble sugars, structural carbohydrate, moisture, ash, fat, carbohydrates including soluble sugars and dietary fibre, protein and oil) and for mineral (Na, K, Ca, Mg, P, Fe) and vitamin (A, E, B1, B2, niacin, B6, folate, C) content fell within the range expected of commercial tomato fruit and fruit purees.</p>\n\n<p style="text-align: justify;">Analysis of known anti-nutritional factors and potential toxins (lectins and alpha-tomatine, solanine, chaconine, tyramine, nicotine and serotonin) demonstrated that a similar range of concentrations of these compounds are present in both modified and unmodified fruit and tomato paste.</p>\n\n<p style="text-align: justify;">Alpha-tomatine is the principal naturally occurring glycoalkaloid in tomato, and the level of alpha-tomatine decreases as the fruit matures, so that the amounts in vine-ripened red tomatoes are negligible. Solanine and chaconine, which are the main glycoalkaloids occurring in potato, have been found in tomato in lesser amounts. The level of a-tomatine in tomato paste prepared from transgenic line F was 58 ppm as compared with 74 ppm for the unmodified TGT7 parental line. The additional glycoalkaloids, solanine and chaconine, were undetectable in either the transgenic or unmodified lines. An analysis of the levels of biogenic amines (tyramine, tryptamine and serotonin), which are considered as potential toxins in tomato, did not reveal any significant differences in the respective concentrations of these compounds in raw tomatoes from either transgenic line F or the unmodified parental line. Tomatoes from the novel hybrid lines 1401F and 282F contained undetectable levels of histamine and nicotine, as did their unmodified counterparts. Other than reduced polygalacturonase activity, the disease, pest and other agronomic characteristics of the 1401F, H282F, 11013F and 7913F hybrids were comparable to the unmodified hybrids.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The reduced synthesis of native PG and the presence of the novel protein NPTII were not judged to have any potential for human toxicity or allergenicity. Polygalacturonase is a natural component of all food plants. The partial sense PG gene present in transformation event F was identical to the corresponding endogenous tomato gene and conferred no additional risks. The antisense PG gene did not encode for any new protein products, and therefore should not have any toxic properties.</p>\n\n<p style="text-align: justify;">Heat processing ensures that the enzyme NPTII does not survive in a biologically active form. Regular human consumption of tomato products containing the heat-denatured protein has not caused recognized problems relating to toxicity or allergenicity. Neither effect would have been expected as judged by comparisons of amino acid sequences made with known antigens, the published lack of effects of the intact NPTII protein in chronic toxicity studies in rats and the recorded ease of degradation of this protein in the digestive tract.</p>\n', 'Enabled', NULL, '2013-08-29 23:32:56'),
(41, 30, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">There was no reason to believe that the development of virus-resistant squash plants would result in a change in fresh marketing or processing procedures. Most yellow crookneck squash are consumed as a raw table vegetable or processed for the frozen food market. The fruit of ZW-20 is intended primarily for human consumption and the genetic modification will not result in any change in the consumption pattern for this product. Consequently, the dietary exposure to this product is anticipated to be the same as for other commercially available squash lines.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">A compositional analysis was conducted on transgenic ZW-20 squash and the non-transformed parental variety in three different locations. The analysis of nutrients from transgenic ZW-20 squash and non-transgenic squash revealed only small differences that were within the range of variability normally reported for squash. It was concluded that there were no significant differences in the content of protein, moisture, fat, ash, total dietary fibre, carbohydrates, calories, fructose, glucose, sucrose, lactose, maltose, vitamin C, beta-carotene, vitamin A, calcium, iron, and sodium. The consumption of products from modified squash would have no significant impact on the nutritional quality of the food supply.</p>\n\n<p style="text-align: justify;">Cucurbitis plants, such as squash, produce alkaloids classified as cucurbitacins, bitter-tasting compounds that discourages feeding by herbivores. It was reported that cucurbitacin B and cucurbitacin E are detectable by taste at sensitivity levels as low as 1 &ndash;10 ppb. A standard test in plant breeding for the presence of cucurbitacins involves tasting the product to determine its bitterness. Both the transgenic squash line ZW-20 and its parent variety were non-bitter.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The WMV2 and ZYMV coat protein sequences were compared to databases of known protein toxins and did not show homologies with known mammalian protein toxins. The history of known safe consumption of these proteins from virus-infected plant products provides additional evidence of lack of toxicity.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The WMV2 and ZYMV coat proteins do not possess characteristics typical of known protein allergens. Comparisons of the deduced amino acid sequence for each of these proteins with the sequences of known protein allergens did not reveal any significant homologies. The WMV2 and ZYMV coat proteins are extremely unlikely to be allergens.</p>\n', 'Enabled', NULL, '2013-08-29 22:41:11'),
(42, 38, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">There was no reason to believe that the development of virus-resistant squash plants would result in a change in fresh marketing or processing procedures for squash. Most yellow crookneck squash are consumed as a raw table vegetable or processed for the frozen food market. The fruit of CZW-3 is intended primarily for human consumption and the genetic modification will not result in any change in the consumption pattern for this product. Consequently, the dietary exposure to this product is anticipated to be the same as for other commercially available squash lines.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">A compositional analysis conducted on transgenic CZW-3 squash and the non-transformed parental variety revealed only small differences that were within the range of variability normally reported for squash. It was concluded that there were no significant differences in the content of protein, moisture, fat, ash, dietary fibre, carbohydrates, calories, fructose, glucose, sucrose, lactose, maltose, vitamin C, beta-carotene, vitamin A, calcium, iron, and sodium.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Cucurbitis plants, such as squash, produce alkaloids classified as cucurbitacins, bitter-tasting compounds that discourages feeding by herbivores. It was reported that cucurbitacin B and cucurbitacin E are detectable by taste at sensitivity levels as low as 1&ndash;10 ppb. A standard test in plant breeding for the presence of cucurbitacins involves tasting the product to determine its bitterness. The transgenic squash line CZW-3 and the parent variety were both non-bitter.</p>\n\n<p style="text-align: justify;">The CMV, WMV2 and ZYMV coat protein sequences were compared to databases of known protein toxins and did not show homologies with known mammalian protein toxins. The history of known safe consumption of these proteins from virus-infected plant products provides additional evidence of lack of toxicity.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">The CMV, WMV2 and ZYMV coat proteins do not possess characteristics typical of known protein allergens. There were no regions of homology when the deduced amino acid sequences of these introduced proteins were compared to the amino acid sequences of known protein allergens. The CMV, WMV2 and ZYMV coat proteins are extremely unlikely to be allergens.</p>\n', 'Enabled', NULL, '2013-08-29 22:53:49'),
(43, 56, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of the modified tomato line 5345 will be as both fresh and processed tomato products. Fresh market tomatoes are eaten whole and sliced or diced in a variety of foods. Processed tomatoes are consumed in the form of soups, preserves, ketchup, paste and prepared sauces. The genetic modification introduced into this transgenic line will not result in any change in the consumption pattern for fresh or processed tomato products. Line 5345 is expected to replace other tomato cultivars currently in use due to improved quality and handling characteristics. Hence, it will provide an alternate or additional choice to consumers and food manufacturers.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional analyses were conducted to compare transgenic line 5345 tomato fruit with fruit obtained from control non-transgenic plants grown and processed under the same conditions. The measured parameters included total solids, protein, ash, carbohydrates, calories, vitamin A, vitamin C, and folic acid. There were no statistically significant differences for any of the parameters between insect-resistant 5345 tomatoes and control tomatoes. The presence of NPTII protein was judged to be insignificant with respect to any human health risk due to exposure. The consumption of this product will, therefore, have no significant impact on the nutritional quality of the food supply in Canada and the United States.</p>\n\n<p style="text-align: justify;">Tomatoes produce naturally occurring glycoalkaloids, alpha-tomatine being the most common. The level of alpha-tomatine decreases as the fruit matures so that the amounts in vine-ripened red tomatoes are negligible. The concentration of alpha-tomatine in immature tomatoes from transgenic line 5345 was 5.15 mg/100g fresh weight tissue, as compared with 3.79 mg/100g fresh weight tissue for the unmodified parental line. However, these levels evened out once the fruit ripened into mature red tomatoes and were within the range of alpha-tomatine levels reported in the literature for tomatoes (4.9-90 mg/100g fresh fruit).</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The likelihood of the Cry1Ac protein being allergenic was judged to be remote. No homologies were found when the deduced amino acid sequence of the introduced protein was 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, and molecular weight. The Cry1Ac protein does not possess these characteristics normally associated with food allergens.</p>\n', 'Enabled', NULL, '2013-08-29 23:30:43'),
(44, 55, '<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The levels of proximates (moisture, ash, fat, protein, total dietary fibre, and carbohydrates) were determined in samples of grain, straw, and various processed fractions (<i>e.g.,</i> rice hulls, brown rice, parboiled brown rice, polished rice, rice flour, rice bran, bran oil) from LLRICE62 and LLRICE06 (sprayed and unsprayed with glufosinate ammonium herbicide) and found to be within the normal range reported in the literature for commercial rice varieties. The amino acid and fatty acid profiles of grain from these transgenic varieties were similar to those of non-transgenic control varieties tested at the same time, and comparable to values reported in the scientific literature.</p>\n\n<p style="text-align: justify;">Rice contains a small number of antinutritional factors that are concentrated in the bran fraction and which, except for phytic acid, are subject to heat denaturation (inactivation). These antinutrients include: phytic acid, which is a storage form of phosphorus in plant seeds but also chelates calcium, zinc, iron, and magnesium in the digestive tract of animals thus interfering with absorption of these nutrients; trypsin inhibitor; and lectins, which are a class of proteins with specific binding affinities for particular carbohydrate moieties present on glycoproteins present in cell walls and cell plasma membranes, and have been associated with a range of antinutritive effects and some disease pathologies.</p>\n\n<p style="text-align: justify;">The levels of trypsin inhibitor and lectins in non-transgenic and transgenic LLRICE06 rough grain were reported to be below the limit of detection, and the phytic acid content did not vary significantly between transgenic and non-transgenic varieties.</p>\n\n<p style="text-align: justify;">The lack of any changes to nutritional composition and quality were also confirmed in a 42-day male broiler chicken feeding study.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">The PAT enzyme does not have the characteristics of a toxin. It is specific for L?phosphinothricin and has no homology to proteins other than to similar PAT encoding genes from other organisms. In summary, no adverse effects were predicted given that the PAT enzyme is a minor constituent of human and animal food</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Searches of public amino acid sequence databases did not reveal any homologies between the deduced amino acid sequence of the introduced PAT protein and sequences of known toxins or allergens. The PAT enzyme does not exhibit the characteristics of an allergen. The PAT enzyme is both heat and acid labile, and looses 100% of its activity after cooking for 30 minutes at 75C. The enzyme is also inactivated after 30 minutes at a pH level of 4 or less. Should cooking not destroy the enzyme, it would be subject to oral ingestion by humans and subsequent rapid digestion. It was shown that PAT was degraded within minutes in simulated gastric juices.</p>\n', 'Enabled', NULL, '2013-08-29 23:28:47'),
(45, 31, '<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Papaya is a tropical fruit crop that is normally consumed fresh and is valued as a rich source of vitamins A and C. In assessing the nutritional composition, samples of fruit from transgenic and non-transgenic control plants were analyzed for vitamins A and C, and total soluble solids (TSS), which is a measure of sugar content. In some cases, the levels of TSS were compared between PRSV-infected fruit and non-infected fruit.</p>\n\n<p style="text-align: justify;">For plants grown in PRSV-infested locations, there was a slightly higher observed level of TSS in transgenic fruit than in PRSV-infected non-transgenic fruit. This difference was not observed when comparisons to non-infected non-transgenic fruit were made.</p>\n\n<p style="text-align: justify;">The vitamin A content of transgenic line 55-1 was comparable to other red-pigmented varieties of papaya and was within the range normally reported for several commercial papaya varieties. Vitamin C content was observed to by slightly lower in transgenic line 55-1 compared to non-transgenic papayas, but was within the range reported for papaya in the literature. Because a number of factors, including ripeness of fruits and growing conditions, can affect vitamin content, this variation was not considered a significant concern. The amount of vitamin C in line 55-1 represents a high level of vitamin C for a food product (49.4-53.6 mg/100g).</p>\n\n<p style="text-align: justify;"><b>Endogenous Toxicants</b></p>\n\n<p style="text-align: justify;">The presence of benzyl isothiocyanate (BITC) in the latex of green papaya tissues has been linked to incidents of spontaneous abortions in pregnant women and with a higher incidence of prostate cancer in Japanese men over the age of 70. Because ripe papaya fruits have no latex they also have virtually no BITC content, and, therefore, the consumption of ripe fruit would not be expected to be linked to any abortifactant effects. The levels of BITC were measured by gas chromatography in extracts from immature and ripe fruits obtained from transgenic papaya and three varieties of non-transgenic control papayas, and there were no significant differences observed between samples derived from transgenic or non-transgenic plants, respectively. It was noted that the isothiocyanate concentrations in ripe papaya fruits are 10 to 100 times lower than similar values reported for other foods, such as broccoli, Brussels sprouts, and cabbage.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">There is a history of safe consumption of PRSV CP derived from virus-infected papaya fruit, and there is no indication that the form of the CP expressed in transgenic papaya is materially different in any way that would affect its potential for toxic or allergenic effect. Additionally, the PRSV CP does not possess any of the physiochemical properties normally associated with protein allergens or toxins, such as heat stability and resistance to digestion by simulated gastric fluids. Also, there were no regions of homology when the deduced amino acid sequence of PRSV CP was compared to the amino acid sequences of known protein allergens or toxins.</p>\n', 'Enabled', NULL, '2013-08-29 22:43:45'),
(46, 45, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Approximately 26% of the world sugar consumed and 47% of the sugar consumed in the United States is produced from sugar beets. Sugar beet is generally converted directly to refined white sugar (which is composed almost entirely of sucrose) through extensive purification processes. The PAT and NPTII proteins were expressed at low levels in the sugar beet roots and tops, and neither protein was detected in refined sugar or molasses derived from sugar beet T120-7, indicating no likelihood for exposure to these proteins from these products.</p>\n\n<p style="text-align: justify;">Sugar beet pulp is a by-product and is normally dried and pelleted for use as a livestock feed. In recent years, it has been purified and used as an additive, at less than 1%, in some specific foods such as food fibre for breakfast cereals etc. The PAT protein was not detected in the pulp and NPTII was detected at very low levels.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The transgenic T120-7 line was compared with nontransgenic sugar beets on the basis of numerous compositional components, including crude fat, crude protein, fibre, ash, carbohydrate, calories, calcium, magnesium, phosphorus, potassium, and sodium. With the exception of fibre content, no statistically significant differences were observed. The differences in fibre content were ascribed to environmental factors associated with different growing locations and conditions.</p>\n\n<p style="text-align: justify;">The process fractions, refined sugar, molasses and dried pulp, were assessed for the proximate variables: fatty acids, amino acids, minerals and sugar profiles. Analysis of the dried pulp fraction revealed differences for ash content and some amino acids. It was determined that these differences in nutrient content would not impact on animal nutrition, as dried pulp comprises only a portion, less than 25%, of the total diet for cattle feed use. The molasses fraction revealed differences in fat, protein, calcium, C10:0 and some amino acids. These differences were small and not expected to impact the nutritional content of animal feed. Analysis of the refined sugar fraction showed a difference in tryptophan levels. Importantly, there were no significant differences between transgenic and nontransgenic sugar beets in carbohydrate content, which is the major nutrient in refined sugar (98%).</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">It was determined that the PAT enzyme has a very low potential for toxic or allergenic effects based on its physiochemical characteristics (<i>e.g.</i>, rapid breakdown under mammalian digestive conditions using simulated gastric and intestinal fluids, and lack of heat stability), its low concentrations in plant tissues and thus food or livestock feed products derived from them, and the lack of amino acid sequence homology with any known protein toxins or allergens.</p>\n', 'Enabled', NULL, '2013-08-29 23:04:22'),
(47, 50, '<p><b>Nutritional Data</b></p>\n\n<p>Samples of grain and forage from transgenic and non-transgenic control lines were subjected to compositional analyses measuring the levels of protein, fat, ash, calcium and phosphorous. Forage samples were also analyzed for crude fibre content. For forage, the levels of analyzed components were found to be comparable between the male-sterile lines, between these lines and non-transgenic control lines, and to previously published literature values. With the exception of calcium levels, which were comparable between the male-sterile and non-transgenic control lines but lower than literature values, similar results were reported for the compositional analyses of grain samples. The lower calcium levels were attributed to an alteration in the analytical method.</p>\n\n<p>Analyses of fatty acids (C16:0, palmitic; C18:0, stearic; C18:1, oleic; C18:2, linoleic; and C18:3, linolenic) and amino acids in samples from each male-sterile line and non-transgenic control lines did not reveal any significant differences in the respective value of each analyte. Except for the levels of a few amino acids, which were lower than those reported in the literature for commercial maize hybrids, the values measured for each analyte were within the range reported in the scientific literature. The differences noted in the levels of a few amino acids were likely due to the genetic background of the inbred parental lines relative to those lines analyzed in previously published studies.</p>\n\n<p><b>Toxicity and Allergenicity</b></p>\n\n<p>Previous studies have demonstrated that the PAT protein has a very low potential to be toxic or allergenic. The enzyme possesses none of the physiochemical characteristics commonly associated with known toxins or allergens, such as resistance to thermal or proteolytic degradation. The amino acid sequence of the PAT protein does not share homology with the sequences of known protein toxins and allergens, and in acute toxicity testing with laboratory mammals, adverse effects have never been observed.</p>\n', 'Enabled', NULL, '2013-08-29 23:13:11'),
(48, 28, '<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Forage and grain from TC1507 maize were analyzed for nutritional composition and compared to the nutritional composition of non-transgenic versions of the same maize hybrids. With respect to forage, there were no significant differences in the respective levels of protein, fat, neutral detergent fibre (NDF), or ash between the transgenic or non-transgenic control lines. The level of acid detergent fibre (ADF) in TC1507 was lower than the control line, but remained within the range of values reported in the scientific literature. Analyses of calcium and phosphorus in forage from TC1507 and the control non-transgenic line were determined to be 0.22 and 0.23 per cent, and 0.25 and 0.24 per cent, respectively.</p>\n\n<p style="text-align: justify;">Grain from TC1507 was found to have similar levels of protein, ADF, NDF and ash as grain from non-transgenic maize hybrids, however, the level of fat was significantly lower. This lower fat content was not considered biologically significant as it was still within the range of values reported for other commercial maize varieties. In examining the fatty acid profile, it was determined that the transgenic line had lower levels of stearic and oleic acid but higher levels of linoleic and linolenic acids than the non-transgenic control. Although differences were noted, they remained within the normal range of variation reported for maize grain. The levels of calcium, phosphorus, copper, iron, magnesium, manganese, and zinc in TC1507 grain were similar to levels measured in grain from the non-transgenic control line. The levels of essential amino acids in TC1507 grain were within the norms reported in the literature. With respect to vitamins, TC1507 had lower levels of vitamin B1 but higher levels of total tocopherols than the non-transgenic control. Although different, these values were within published ranges.</p>\n\n<p style="text-align: justify;">There were no differences in the levels of phytic acid between the transgenic and non-transgenic lines, and the level of trypsin inhibitor in both TC1507 and the non-transgenic control was below the threshold of detection (2000 TIU/g).</p>\n', 'Enabled', NULL, '2013-08-29 22:37:39');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(49, 75, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">In the United States and Canada, the primary form of consumption for field maize is as maize-based food ingredients with little whole kernel or processed field maize directly consumed by comparison. Field maize is used as a raw material for the manufacture of starch, which is in turn converted to a variety of sweeteners (such as high fructose maize syrup) and fermentation products (ethanol). The germ of the maize kernel is also used for the production of maize oil. These materials are commonly found in many foods, resulting in wide population dietary exposure to all maize products. The human food uses of grain from MON 863 are not expected to be different from the uses of non-transgenic field maize varieties and therefore the dietary exposure of the general population to MON 863 grain should not be different from that of other field maize varieties.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional analyses were conducted on plant material (forage and grain) obtained from MON 863 and non-transgenic parental control plants grown at four replicated field trial sites in the United States. As a further comparison, similar analyses were conducted on plant material derived from nine different non-transgenic commercial maize hybrids grown under field conditions at two replicated sites.</p>\n\n<p style="text-align: justify;">Grain samples were analyzed for levels of protein, fat, ash, moisture, carbohydrates, acid detergent fibre (ADF), neutral detergent fibre (NDF), amino acids, fatty acids, vitamin E, minerals [calcium, copper, iron, magnesium (Mg), manganese (Mn), phosphorus (P), potassium, sodium, and zinc (Zn)], phytic acid, and trypsin inhibitor. Other than for the exceptions noted below, there were no statistical difference in the measured values for each of these parameters between MON 863 and the non-transgenic control line, and in each case the values obtained from both were within the range of values for the nine control varieties and those reported in the literature. The exceptions noted were:</p>\n\n<ol>\n	<li style="text-align: justify;">Carbohydrate levels and levels of the non-essential amino acids cysteine, aspartic acid, and glycine were higher in MON 863 than in the non-transgenic parental control, but were within the range of values measured for the nine commercial varieties.</li>\n	<li style="text-align: justify;">Levels of protein, the essential amino acids leucine and phenylalanine, and the non-essential amino acid glutamic acid, were lower in MON 863 than in the non-transgenic parental control, yet were within the range of values measured for the nine commercial varieties.</li>\n	<li style="text-align: justify;">The levels of P, Mg, Zn, Mn, and vitamin E were lower in MON 863 than in the non-transgenic parental control, but were within the range measured for the nine commercial varieties and those reported in the scientific literature.</li>\n	<li style="text-align: justify;">The level of phytic acid (a phosphorus-binding dietary antinutrient) was lower in MON 863 than in the non-transgenic parental control, but within the range of values measured for the nine commercial varieties.</li>\n</ol>\n\n<p style="text-align: justify;">&nbsp;</p>\n\n<p style="text-align: justify;">Data on levels of protein, fat, ash, moisture, carbohydrates, ADF, and NDF, obtained from forage samples did not reveal any significant differences between MON 863 and the non-transgenic parental control, and all values fell within the range measured for the nine commercial varieties</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;">Cry3Bb1 protein extracted and purified from a heterologous <i>E. coli</i> fermentation system was used as the test material for an acute oral toxicity study with mice. The identical <i>cry3Bb1</i> coding sequence used in the transformation of event MON 863 was used in the transformation of <i>E. coli</i>. The protein expressed by <i>E. coli</i> was assessed and found to be physicochemically and functionally equivalent to that expressed in plant tissue. The bacteria expression platform was used since a sufficient amount of the protein could not be purified from plant tissue. In the acute gavage study, the No Observed Adverse Effect Level (NOAEL) was found to exceed 3200 mg/kg the maximum dose achievable. At that level, no mortality or grossly observable adverse effects were noted.</p>\n\n<p style="text-align: justify;">The NOAEL was considered to be four orders of magnitude (5.8 X 104) times greater than the expected human intake of Cry3Bb1 protein from MON 863 maize. The NOAEL was 1000 times greater than the expected livestock dietary intake of Cry3Bb1 protein from MON 863 maize.</p>\n\n<p style="text-align: justify;">The sequence of amino acids making Cry3Bb1 protein was compared to that of known toxins. There was no sequence homology noted with toxins. As well, there were no structural similarities noted between Cry3Bb1 and known toxins.<br />\nThese factors indicated that Cry3Bb1 had a low probability to exhibit toxicity to humans or livestock consuming MON 863 maize or products derived from it.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Current scientific knowledge indicates that many food allergens tend to be abundant proteins within the food product, resistant to proteolytic digestion and heat inactivation and are often glycosylated. The Cry3b1 protein was assessed for allergenicity by examining its digestibility; amino acid sequence homology to known allergens; its glycosylation profile; and history of safe use of microbial sprays.</p>\n\n<p style="text-align: justify;">The results of an <i>in vitro</i> digestive fate study using simulated gastric fluid (SGF) indicated that Cry3Bb1 protein degraded to nondetectable levels in 15 seconds. The protein is also quickly deactivated upon exposure to heat. The protein was compared to known allergens and did not exhibit amino acid sequence homology. The Cry3Bb1 protein is not glycosylated. As well, the protein is present only at very low levels in edible portions of maize.</p>\n\n<p style="text-align: justify;">The long history of use of <i>Bt</i> toxins in microbial sprays has produced numerous safety studies which have demonstrated its low mammalian toxicity. As well, there have been no confirmed cases of allergic reactions to Cry proteins in scientific literature.</p>\n\n<p style="text-align: justify;">From these collective data it was judged that Cry3Bb1 protein in MON 863 maize was unlikely to be a human allergen.</p>\n', 'Enabled', NULL, '2013-08-30 12:26:09'),
(50, 76, '<p style="text-align: justify;"><b>Nutritional Data (Livestock Feed Purposes)</b></p>\n\n<p style="text-align: justify;">Data on fatty acid profiles, protein content, amino acid composition, crude fibre, ash, phytate, and moisture content were provided for grain samples from lines CL121, CL141, and CFX51, and five commercial varieties grown in three locations in the United States. Comparisons of these parameters between the herbicide-tolerant lines and conventional commercial varieties did not reveal any biologically significant differences.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The single amino acid change within the native ALS enzyme was not anticipated to have any effect on the potential toxicity or allergenicity of this protein. The unmodified form of this enzyme does not display amino acid sequence homology with known protein toxins or allergens. Studies on the modified ALS protein isolated from the original mutant line, 93AS3510, demonstrated that it was rapidly inactivated by heat (1 minute at 100&deg;C) and was completely degraded within 5 minutes of treatment with trypsin. Susceptibility to heat inactivation and sensitivity to proteolytic degradation are not characteristics of known protein toxins or allergens.</p>\n\n<p style="text-align: justify;">Measurements of the concentrations of normally occurring rice antinutritional factors (<i>e.g.</i>, phytic acid, trypsin inhibitor, and lectin) did not reveal any differences between these herbicide-tolerant lines and five conventional commercial rice varieties. For all of these varieties, the concentrations of trypsin inhibitor and hemagglutinins (i.e. lectins) were below the threshold of detection.</p>\n', 'Enabled', NULL, '2013-08-29 23:46:24'),
(51, 74, '<p style="text-align: justify;"><b>Nutritional Data</b><br />\r\nCompositional analyses were performed on grain and forage samples of NK603 (treated with glyphosate) and the non-transformed parental control line together with a number of other commercial maize hybrids planted at trial sites in the U.S. and Europe. Analyses of grain samples included measurements of proximates (protein, fat, ash, moisture), acid detergent fibre (ADF), neutral detergent fibre (NDF), amino acids, fatty acids, vitamin E, minerals (calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc), and the antinutritional components, phytic acid and trypsin inhibitor.<br />\r\n<br />\r\nIn all of these tests, small statistical differences between NK603 and control lines were observed only in: six amino acids (alanine, arginine, glutamic acid, histidine, lysine, and methionine) as measured in grain from European trials (no differences were observed in material from U.S. trials); and stearic (C18:0) acid levels. Overall, these differences were not consistent across all trial sites and they were considered to reflect random variation. All compositional results were within the ranges observed for commercial non-transformed lines.<br />\r\n<br />\r\nThe nutritional quality of NK603 grain was assessed in feeding trials with broiler chickens, finisher swine, and laboratory rats. These studies showed that there were no differences between the transformed and non-transformed maize.<br />\r\n<br />\r\n<b>Toxicity</b><br />\r\nThe CP4 EPSPS gene encodes a single polypeptide of 455 amino acids (47.6 kDa) which exhibits about 50% amino acid sequence similarity with the analogous plant EPSPS enzyme. The family of bacterial and plant EPSPS proteins are not known to display any toxic or allergenic properties. The potential toxicity of the CP4 EPSPS protein was assessed by comparing its amino acid sequence against a database of 4,677 protein sequences (not all unique) that have been associated with toxicity, and in an acute oral toxicity study in mice. The CP4 EPSPS protein did not display any sequence homology with known protein toxins and did not result in any adverse effects on test animals (50 males, 50 females) receiving doses up to 400 mg/kg of bacterially derived CP4 EPSPS protein. The single amino acid substitution within the CP4 EPSPS L214P protein did not alter the sequence comparison results.<br />\r\n<br />\r\n<b>Allergenicity</b><br />\r\nThe CP4 EPSPS encoding gene was not derived from an organism known to cause allergic reactions and the allergenic potential of this protein was further evaluated by comparing its amino acid sequence against a database of known allergens, and by assessing its stability to digestion in the presence of simulated gastric fluids. There was no sequence homology between CP4 EPSPS and known allergens when checked against a database of 567 protein sequences using an 8-amino acid length window. As assessed by Western immunoblot analysis, the CP4 EPSPS was rapidly degraded (T50 &lt; 15 sec) upon exposure to pepsin-containing simulated gastric fluid or trypsin-containing simulated intestinal fluid (T50 &lt;= 10 min). Similar results were obtained with the variant CP4 EPSPS L214P protein.</p>\r\n', 'Enabled', NULL, '2013-09-04 13:46:42'),
(52, 4, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The human consumption of canola products is limited to the refined oil. Typically, canola oil is used by itself as a salad oil or cooking oil, or blended with other vegetable oils in the manufacture of margarine, shortening, salad oil and cooking oils. Refined edible canola oil consists of purified triglycerides (96-97%) and does not contain any detectable protein. As the nitrilase protein was not found in the refined oil produced from transgenic canola Oxy-235, it can be concluded that there will be no human exposure to these proteins. The genetic modification of Oxy-235 canola will not result in any change in the consumption pattern for this product.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The nutritional composition of Oxy-235 was shown to be equivalent to non-transgenic canola. There were no significant differences in the fatty acid composition of oil from Oxy-235 and unmodified counterparts and all values were within the range of quality standards for canola. It was also found that the modification did not change the levels of sterols, tocopherols, and unsaponifiable matter in crude oil.<br />\nAn analysis of the nutrient value of canola meal from Oxy-235 and non-transgenic canola did not reveal any significant differences in the levels of dry matter, crude fibre, neutral detergent fibre (NDF), acid detergent fibre and lignin (ADF and ADL), crude protein, total fat, soluble sugars, amino acid content as well as gross energy level in seeds and meal. Seeds of Oxy-235 were shown to have the same levels of glucosinolates and erucic acid as commercial canola varieties.</p>\n\n<p style="text-align: justify;">A 28-day rat feeding study was conducted where rats were fed up to 10% canola meal in their food. There were no toxic effects from the study and results were the same regardless of whether the source of canola meal was Oxy-235 or non-transgenic canola.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">It was determined that there were no toxicity or allergenicity concerns with Oxy-235, since refined canola oil is the only product for human consumption and does not contain any detectable amount of protein. The absence of toxicity was further demonstrated by examining the amino aid sequence homology and the characteristics of the novel nitrilase enzyme.</p>\n\n<p style="text-align: justify;">The amino acid sequence of the nitrilase protein was compared to the amino acid sequences of known protein toxins and allergens and no significant similarities were found. Furthermore, the nitrilase protein did not share characteristics common to allergens.</p>\n\n<p style="text-align: justify;">Digestive fate studies demonstrated that the nitrilase protein was rapidly inactivated in mammalian stomach and intestinal fluids by enzymatic degradation and pH-mediated proteolysis. To confirm the absence of toxic effects from nitrilase protein, a 14-day sub-acute toxicity feeding study was conducted with mice feed bacterial nitrilase protein. There were no toxic effects observed.</p>\n', 'Enabled', NULL, '2013-08-29 20:40:05'),
(53, 86, '<p style="text-align: justify;"><b>Dietary exposure</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in X81359 will not result in any change in the consumption or use pattern of sunflower oil and products derived from the oil and the meal. The oil and meal from X81359 are therefore expected to be used in applications similar to other sunflower and vegetable oils by the food and feed industry. X81359 is also the result of several backcrosses into NuSun sunflower lines. The oil from these sunflower lines have an altered fatty acid profile, and are termed &ldquo;mid-oleic.&rdquo; Due to this altered fatty acid profile, oil derived from Clearfield&trade; sunflower line X81359 will require a modified common name to differentiate the oil from traditional sunflower oils in the marketplace.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The nutritional composition of X81359 sunflower was assessed in whole sunflower grain and compared to comparator line, 8377NS, and other commercial sunflower cultivars. Samples for analysis were obtained from trials at six location years in the United States. The nutritional components included: crude protein, crude fat, crude fibre; branched chain amino acids (valine, isoleucine, leucine); essential amino acids (cysteine, methionine, threonine and lysine); B vitamins (thiamine, niacin, pantothenic acid, pyridoxine, riboflavin, and folic acid); minerals (phosphorus, zinc, magnesium and iron); vitamin E; and fatty acids. Statistically significant differences were observed in the levels of crude protein, threonine, tryptophan, calcium and magnesium. These differences were not biologically significant, and were within the normal range of variation reported for NuSun hybrids. Significant differences were observed in the levels of some fatty acids, such as stearic acid; however, these levels also fell within the ranges determined for other mid-oleic NuSun sunflower oils. The overall nutritional composition of X81359 was therefore determined to be equivalent to the comparator line 8377NS, and to commercial sunflower cultivars, including NuSun hybrids.</p>\n\n<p style="text-align: justify;">The anti-nutrients phytic acid and trypsin inhibitor were measured in X81359 and 8377NS. Phytic acid occurs naturally in sunflower and in cereals. It is indigestible by humans and non-ruminant livestock, and inhibits the absorption of iron and other minerals. Trypsin inhibitor interferes with the enzymes involved in protein digestion. Phytic acid levels in X81359 were not different from those of the comparator line 8377NS, and levels of trypsin inhibitor in both lines were below the limit of detection.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The impact of single point mutations that confer tolerance of various plant AHAS to imidazolinone herbicides, on the toxic and allergenic potential of the protein has been reviewed previously by Health Canada and the Canadian Food Inspection Agency. No toxicological or allergenic concern was introduced at the level of exposure to AHAS in those products. In the case of oil produced from X81359 sunflower, extensive processing removes protein residues from the oil, and consequently, exposure to the mutated AHAS protein is expected to be negligible.</p>\n\n<p style="text-align: justify;">The AHAS enzyme does not possess the physicochemical properties of toxins and allergens, such as resistance to heat and trypsin degradation. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. Data from studies on the AHAS from X81359 demonstrated the inactivation of the enzyme after 1 minute of heating at 100&deg;C, and its complete degradation in trypsin within 60 minutes of exposure. The unmodified form of AHAS also shows no amino acid similarity to known toxins and allergens, and the modified AHAS differs by only one amino acid. Evidence was also provided to show that the protein components of X81359 were not altered compared to those of unmodified control. Results from HPLC on protein extracts demonstrated similar protein banding pattern in X81359 compared to the unmodified sunflower cultivars. The results of these investigations led to the conclusion that X81359 sunflower did not demonstrate any potential for toxicity and allergenicity compared to conventional unmodified sunflower.</p>\n', 'Enabled', NULL, '2013-08-29 23:57:21'),
(54, 87, '<p style="text-align: justify;"><b>Dietary Exposure:</b></p>\n\n<p style="text-align: justify;">AP602CL Clearfield wheat is expected to be used in similar applications as other wheat varieties. There were no expected changes in gluten content in this variety, thus presenting no new or additional concern for individuals with celiac disease.</p>\n\n<p style="text-align: justify;"><b>Nutritional Analysis:</b></p>\n\n<p style="text-align: justify;">Analysis for nutritional and anti-nutritional components of grain derived from AP602CL Clearfield wheat revealed no significant difference from grain derived from the parent line Gunner wheat. AP602CL had slightly lower fat content, lower oleic acid content and higher threonine content than Gunner, but these differences were determined to have no impact on livestock nutrition. There were no other substantial differences between AP602CL and Gunner in terms of nutritional composition.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity:</b></p>\n\n<p style="text-align: justify;">The expression of the modified AHAS enzyme is not associated with any toxicity or allergenicity concerns. AHAS is expressed at very low amounts in the edible portion of wheat, its activity is heat-labile and degrades in the human gastrointestinal tract. The modified AHAS enzyme is not homologous to known allergens and is not different from the unmodified AHAS in its similarity to known allergens. AP602CL wheat does not express any other new proteins or altered amounts of other proteins, including known wheat allergens. It is also unlikely that AP602CL has unintended secondary mutagens that may cause effects on livestock or bystanders.</p>\n', 'Enabled', NULL, '2013-08-29 23:58:35'),
(55, 77, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Cotton, <i>Gossypium hirsutum</i> L., is grown worldwide primarily as a source of fibre in textile manufacturing. Cottonseed, the by-product of fibre production, is processed into four major products: oil, meal, hulls, and linters. Cottonseed oil is routinely used in human food. Linters are also used for human food, but to a lesser extent than oil. Both have a long history of safe use. Cottonseed meal and hulls are used in animal feed.</p>\n\n<p style="text-align: justify;">Cottonseed oil used for human consumption is highly purified, and contains no detectable proteins. Refined cottonseed oil is used as frying oil, salad and cooking oil and in various processed foods such as mayonnaise, salad dressing, shortening, and margarine. Linters are also highly processed to obtain pure cellulose for use in casings for processed meat products such as bologna, sausages and frankfurters. Such cellulose is also used to thicken ice cream and salad dressings.</p>\n\n<p style="text-align: justify;">Whole cottonseed is used as an energy feed for dairy cows and as a protein supplement in feed for other livestock. Hulls are used as a fibre component in livestock feeds.</p>\n\n<p style="text-align: justify;"><b>Nutritional data</b></p>\n\n<p style="text-align: justify;">Compositional analyses were conducted on cottonseed samples from cotton line MON 15985, the parental control DP50B (MON 531 hybrid), the non-transgenic ancestral line DP50 and four commercially available non-transgenic varieties. The samples were collected from eight field trial sites at various locations in cotton producing areas of the United States. The cottonseed was analysed for protein, fat, ash, moisture, carbohydrate, fibre and caloric content, amino acid and fatty acid composition, mineral content, vitamin E and the anti-nutritional elements gossypol and cyclopropenoid fatty acid.</p>\n\n<p style="text-align: justify;">To perform compositional analysis on cottonseed oil, the cottonseed was pooled across the eight field sites creating one composite sample per cotton line. Each pooled sample was then processed into oil and analyzed for fatty acid composition, vitamin E content, and levels of the anti-nutritional factor gossypol and cyclopropenoid fatty acid.<br />\nFor cottonseed samples, protein, fat, carbohydrate, moisture, caloric content, amino acids and minerals in the MON 15985 line and the parent lines were not significantly different and were within the published ranges and reference ranges for commercial varieties.</p>\n\n<p style="text-align: justify;">During the fatty acid composition analyses, small but statistically significant differences in the mean levels of myristic, stearic and linoleic acids were noted between cotton line MON 15985 and its parent. The values for these fatty acids fell within the commercial cotton ranges and were therefore not considered biologically significant.<br />\nCyclopropenoid fatty acid levels were analysed and found to be slightly higher in cotton line MON 15985 as compared to the parental control. These levels were found to be within the reference ranges for commercial cotton varieties. There was no difference in the levels of gossypol found in the MON 15985 line compared to the parental control or commercial reference varieties. In addition, all lines were analysed for aflatoxins, potent animal toxins and carcinogens, which were not detected in cotton line MON 15985, the parental control, or any of the commercial reference varieties.</p>\n\n<p style="text-align: justify;">The levels of acid detergent fibre (ADF) and neutral detergent fibre (NDF) in cottonseed from line MON 15985, DP50B and DP50 were analysed. NDF was found to be elevated above the range of NDF values published for commercial varieties in all three lines, which were collected in large scale field production plots in Argentina. These NDF values were not significantly different from line to line. The ADF values were found to neither be significantly different from line to line nor were they significantly different from ADF values published in literature.</p>\n\n<p style="text-align: justify;">For oil, there were no differences between the MON 15985 and DP50B lines for fatty acid profile. These fatty acid profiles were also consistent with those determined for the commercial varieties. The level of vitamin E in oil from line MON 15985 was slightly above that determined for the parental varieties and the values obtained from the reference varieties, however it was still within the range reported in literature.</p>\n\n<p style="text-align: justify;">In the analyses of anti-nutritional factors, there was no gossypol detected in the oil of either the MON 15985 line or the parental line. The cyclopropenoid fatty acid levels were found to be similar for the MON 15985 line, its parental line and commercial varieties.</p>\n\n<p style="text-align: justify;">The line MON 15985 was determined to be not materially different in composition from commercial cotton varieties currently under cultivation.</p>\n\n<p style="text-align: justify;">To determine the performance of cottonseed meal derived from cotton event MON 15985 as a livestock feed, feeding trials of channel catfish were conducted. Channel catfish were fed a diet of containing approximately 20% processed cottonseed meal either from line MON 15985, from the parental line or from a non-transformed cotton line. There were no significant differences found between the three groups for survival, weight gain and feed conversion ratios.<br />\nAs ginned cottonseed is used as a feed supplement for dairy cattle, lactating dairy cows were fed cottonseed from the transgenic parental line (DP50B, line MON 15985, the non-transgenic parental line and a transgenic line expressing CP4 EPSPS (Roundup Ready). Cottonseed comprised about 10% of the total dry matter intake of the cows. There was no significant difference in dry matter intake or cottonseed intake for the groups. Milk yield, milk composition, and body condition scores were also comparable across treatments.</p>\n\n<p style="text-align: justify;">From both these studies, it was concluded that processed cottonseed meal and cottonseed can be safely used as livestock feed for catfish and dairy cattle without adversely affected behaviour, growth, feed conversion, or performance.</p>\n\n<p style="text-align: justify;"><b>Toxicity</b></p>\n\n<p style="text-align: justify;"><i>Cry2Ab2</i><br />\nDue to the low levels of Cry2Ab2 produced in cotton tissue, microbially-produced Cry2Ab2 protein was used for acute oral toxicity testing. The microbial form of Cry2Ab2 was determined to be equivalent to plant-expressed Cry2Ab2.<br />\nIn acute oral toxicity testing, mice were exposed to the Cry2Ab2 protein through oral gavage at 1450, 359 and 67 mg/kg body weight and observed over 14 days. There were no treatment-related observable adverse effects noted at these doses. The dose of 1450 mg/kg body weight exceeded the maximum potential exposure to Cry2Ab2 in oil and linters, which is expected to be below 1 ug per day for human dietary exposure.</p>\n\n<p style="text-align: justify;">The Cry2Ab2 protein was also rapidly digested upon exposure to simulated gastric fluid (SGF). Within 15 seconds of exposure to SGF, there were no fragments greater than 2kDa remaining. During simulated intestinal fluid (SIF) digestion, a 50kDa trypsin fragment was produced after 1 minute. This fragment was consistent with the SIF digestion of other <i>Bt</i> proteins in which stable tryptic cores persist.</p>\n\n<p style="text-align: justify;">In addition, <i>Bt</i> proteins in microbial spray formulations have been used for over 30 years with no apparent toxic effects. As well, Cry2Ab2 showed no amino acid homology with known toxins.</p>\n\n<p style="text-align: justify;">These data contributed to a determination of no likely toxic effect of Cry2Ab2.</p>\n\n<p style="text-align: justify;"><i>GUS</i><br />\nGUS protein produced by an <i>E. coli</i> platform was used in an acute oral toxicity study in mice. Mice were subjected to doses of 40, 100 and 400 mg/kg of GUS protein and observed over 8 or 9 days. There were no treatment-related adverse effects observed during the course of the study, nor at the termination of the study. GUS was also found to not be homologous to any known toxins. In SGF and SIF studies, GUS was found to degrade to non-detectable levels in 15 seconds in SGF and lost 91% of its enzymatic activity after 2 hours digestion in SIF. These data contributed to the conclusion that GUS protein is not likely to be toxic when expressed in line MON 15985 cotton.</p>\n\n<p style="text-align: justify;"><b>Allergenicity</b></p>\n\n<p style="text-align: justify;">Current scientific knowledge indicates that most food allergens share common characteristics, such as being present in high concentrations in the food product, resistance to proteolytic digestion and heat activation, and they are often glycosylated. The Cry2Ab2 protein was not derived from an allergenic source, was present only at very low levels in event MON 15985 cottonseed (0.004% of protein present in the seed, &lt;0.25 ppm in oil), was rapidly digested in SGF and SIF and did not exhibit significant amino acid sequence homology with known protein allergens.</p>\n', 'Enabled', NULL, '2013-08-30 12:34:07'),
(56, 92, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification of 281-24-236 cotton would not be expected to result in any change in the consumption pattern of cotton products. The seed, oil and lint fraction 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 line 281-24-236 to null plants and conventional cotton cultivars. Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. There were no detectable proteins in the oil from line 281-24-236. Processed linters are composed of pure (&gt;99%) cellulose and are treated with heat and solvent that would be expected to remove and destroy any residual protein.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The nutritional components of 281-24-236 cottonseed, kernels, toasted meal, hulls and oil were determined analytically and compared to those of the non-transgenic control (a null segregant resulting from several backcrosses of 281-24-236 with both parental lines). Cottonseed analysis included proximates (crude protein, crude fibre, acid detergent fibre, neutral detergent fibre, total fat, ash, and moisture), minerals, amino acids, and fatty acids, and anti-nutrients (cyclopropenoid fatty acids, gossypol [total and free], aflatoxins). Oil analysis included crude fat, crude protein, moisture, fatty acids, anti-nutrients and anti-oxidants. Kernels, toasted meal, hulls were analyzed as appropriate for the particular fraction. Other than small differences in the levels of some components in cotton seed, which were determined to be biologically insignificant, and most likely due to genotypic and environmental effects, the analyses demonstrated that the composition of 281-24-236 cottonseed is comparable to that of the non-transgenic control, and seed of other commercial cotton varieties. The composition of cottonseed oil was also comparable to the non-transgenic control and commercial cottonseed oil. Anti-nutrient levels in 281-24-236 were similar to those of the non-transgenic control and to values published in the literature.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of the Cry1F and PAT proteins in line 281-24-236 was assessed from the following data and information: results of searches for amino acid sequence similarity between the Cry1F and PAT proteins and known toxins and allergens; analysis for possible glycosylation of Cry1F; in-vitro digestibility studies using simulated gastric fluid; assessment of heat stability; and acute oral toxicity studies with mice.</p>\n\n<p style="text-align: justify;">Both the Cry1F and PAT proteins showed no amino acid sequence similarity to known allergens. Both of these proteins were degraded within one minute of exposure to simulated gastric fluid and were no longer detectable by either SDS-PAGE or Western blot analysis. The Cry1F protein was no longer biologically active after exposure to temperatures greater than 75&deg;C. No post-translational glycosylation was detected in cotton-expressed Cry1F protein. Levels of natural toxicants in cotton (<i>e.g.</i>, gossypol) were not significantly different in 281-24-236 cotton compared to the non-transgenic control and conventional cotton varieties.</p>\n\n<p style="text-align: justify;">Results of feeding studies on mammals, birds, soil invertebrates, aquatic organisms, and non-target insects showed no observable adverse effects of either the microbially expressed Cry1F or the protein expressed in cotton tissues. Generally, for most of the species tested, there was at least 5-fold safety margin between the lowest observed effect level and the highest estimated concentration to which these species might be exposed. A 3-fold safety margin was determined for honeybees. An additional non-target insect feeding study was requested by the Environmental Protection Agency (EPA) of the United States as a condition of registration. This study was conducted with the minute pirate bug, an important predatory insect found in cotton fields.</p>\n\n<p style="text-align: justify;">Cry proteins in Bt biopesticide formulations have a long history of safe use, with no evidence of adverse effects, other than insecticidal activity towards lepidopteran insect pests. The Cry1F protein also was expressed at very low levels in the various tissues of 281-24-236 cotton. On the basis of this information, and the results of the various safety studies and sequence homology investigations, a determination was made that 281-24-236 cotton did not demonstrate potential for toxicity or allergenicity compared to conventional cotton varieties.</p>\n', 'Enabled', NULL, '2013-08-30 00:06:30'),
(57, 82, '<p style="text-align: justify;"><b>Dietary Exposure:</b>&nbsp;&nbsp;The genetic modification of LLCotton25 would not be expected to result in any change in the consumption pattern of cotton products. LLCotton25 did not express any novel characteristics with regard to cotton seed, oil, and the lint fraction that would alter the consumption pattern. This was confirmed by comparison of the levels of these fractions, and those of the proximates, and fatty acids in LLCotton25 to the unmodified parent and conventional cotton cultivars.</p>\n\n<p style="text-align: justify;">Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. Processed linters are composed of pure (&gt;99%) cellulose and are treated with heat and solvent that would be expected to remove and destroy any residual protein. PAT protein was detected in linters from LLCotton25; this protein would also be expected to be removed and during heat and solvent treatment. Cottonseed oil for human consumption is highly refined and does not contain detectable levels of protein. The PAT protein was not detected in either crude oil, or the more refined, deodorized oil. The consumption of these cotton fractions would therefore not be expected to result in an increase in exposure to PAT protein.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data:</b>&nbsp;&nbsp;The nutritional components of LLCotton25 cottonseed were determined analytically and compared to those of its parental line, &lsquo;Coker 312.&rsquo; These components included proximates [moisture, ash, fat (ether extract), crude protein, crude fibre, acid detergent fibre (ADF), neutral detergent fibre (NDF), and carbohydrates], amino acids, fatty acids, minerals (calcium, phosphorus, iron, magnesium, potassium, and zinc), and vitamin E. Lint samples were analyzed for crude protein, fat, ash, crude fibre, ADF and NDF. The nutritional composition of the products of cottonseed processing (linters, delinted seed, meal, toasted meal, hull, crude oil and deodorized oil) was also determined, as appropriate for the particular fraction. The data from the nutritional analyses demonstrated that the composition of LLCotton25 cottonseed is comparable to that of the nonmodified parental line &lsquo;Coker 312,&rsquo; and seed of other commercial cotton varieties. The composition of the refined (deodorized) oil fraction was also comparable to Coker 312 and commercial cottonseed oil.</p>\n\n<p style="text-align: justify;">The levels of the anti-nutritional factors phytic acid, gossypol (total and free), and cyclopropenoid fatty acids, were determined in cottonseed of LLCotton25 and Coker 312. The levels of these anti-nutrients in LLCotton25 were comparable to those of Coker 312, and to values published in the literature, except for levels of free gossypol, which were higher in both LLCotton25 and its parental line Coker312. The higher level of gossypol was therefore attributed to genotype, and not to any unintended effect of the genetic modification in LLCotton25.</p>\n\n<p style="text-align: justify;">The feeding performance of LLCotton25 was assessed in a 33-day broiler chicken study. Treatments also included the parental line, and a conventional cotton variety. Cottonseed meal comprised 10% of the total ration fed to the broilers. No differences in animal performance, (weight gain, feed efficiency), feed consumption, and chilled carcass weight were observed among the treatments.</p>\n\n<p style="text-align: justify;"><b>Potential Allergenicity and Toxicity:</b>&nbsp;&nbsp;The potential for toxicity and allergenicity of LLCotton25 was investigated using the following data and information: comparison of the amino acid sequence of the PAT to known toxins and allergens and the assessment potential glycosylation sites using several public databases (<i>e.g.</i>, SwissProt, trEMBL, GeneSequ-Prot); citations from published and unpublished safety studies using the PAT protein (<i>i.e</i>., <i>ex vivo</i> digestibility using pig and cattle gastric fluids, <i>in vitro</i> digestibility using simulated gastric and intestinal fluid conditions, assessment of heat sensitivity, acute intravenous and subchronic oral toxicity studies in rodents); results from a feeding study of broiler chickens using with LLCotton25 cottonseed meal.</p>\n\n<p style="text-align: justify;">The PAT protein in LLCotton25, as expressed by the bar gene, showed no amino acid sequence similarity with known toxins and allergens, and no potential glycosylation sites. The protein was rapidly digested under simulated gastric fluid conditions but demonstrated some resistance to heat degradation. The results of acute and subchronic rodent studies showed no adverse effects of the PAT protein, thereby addressing the concern with regard to the heat stability. The broiler chicken feeding study using cottonseed meal (10% of the total ration) also showed no adverse effects that could be attributed to the PAT protein in LLCotton25.</p>\n\n<p style="text-align: justify;">The PAT protein was expressed at very low levels in LLCotton25 cottonseed and was virtually absent from the oil. This fact, along with negative results of the various safety studies and sequence homology investigations, led to the conclusion that LLCotton25 did not demonstrate any potential for toxicity and allergenicity compared to conventional cotton varieties.</p>\n', 'Enabled', NULL, '2013-08-29 23:53:29'),
(58, 91, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in PWC16 will not result in any change in the consumption pattern of rice and rice-based products. The availability of many rice varieties for cultivation, the diversity of rice varieties in phenotypic traits, and the normal variation in rice composition due to differences in growing conditions, all result in a wide variation in the composition of conventional rice grain. Thus, the cultivation of PWC16 would not be expected to change the dietary exposure in the United States and Canada, any more than commercially available rice cultivars. Furthermore, PWC16 is expected to be used in similar applications as other rice cultivars by the food industry.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">Nutritional components of line PWC16 were measured analytically and compared to those of its parental line, Cypress. These components included crude fat, crude fibre, crude protein, moisture, amino acids, fatty acids, B vitamins, vitamin E, phosphorous, magnesium, iron and zinc. There were no differences between PWC16 and Cypress in the levels of these nutrients, and the nutritional profile was comparable to other commercial rice varieties.</p>\n\n<p style="text-align: justify;">The levels of the anti-nutritional factors phytic acid and trypsin inhibitor were determined in rice grain samples from PWC16 and Cypress. Phytic acid is indigestible by humans and non-ruminant livestock and inhibits the absorption of iron and other minerals. Trypsin inhibitor interferes with normal protein digestion. No differences were found between the modified and unmodified lines for either anti-nutritional factor.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of PWC16 was investigated by examining the amino acid sequence homology and the characteristics of the altered AHAS protein. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. Data from studies on the heat sensitivity and trypsin degradability of the AHAS in PWC16 were submitted and showed similar sensitivity to heat and degradability compared to unmodified AHAS. The unmodified form of AHAS showed no amino acid similarity to known allergens. The amino acid sequence of the mutated AHAS differs by only one amino acid compared to unmodified rice. Data were also submitted to show that levels of endogenous rice allergens in PWC16, such as trypsin inhibitor, were similar to those of conventional cultivated rice. Evidence was also provided to show that the protein components of PWC16 were not altered compared to the unmodified parent &lsquo;Cypress.&rsquo; Results of SDS-PAGE electrophoresis and HPLC showed that no new major proteins or increased protein expression occurred as a result of the mutation to the AHAS enzyme. From these results it was concluded that PWC16 did not demonstrate any potential for toxicity and allergenicity compared to conventional rice varieties.</p>\n', 'Enabled', NULL, '2013-08-30 00:04:37'),
(59, 88, '<p style="text-align: justify;"><b>Dietary exposure</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in Teal 11A will not result in any change in the consumption or use pattern of wheat and wheat-based products. The availability of many wheat cultivars for cultivation, the diversity of wheat in phenotypic traits, and the normal variation in wheat composition due to differences in growing conditions all result in a wide variation in the composition of conventional wheat grain. Since the modification to the AHAS enzyme would not be expected to change the gluten content in Teal 11A, the cultivation and use of this wheat would not result in any new or additional concern for individuals with celiac disease. The cultivation of Teal 11A would not be expected to change the dietary exposure in Canada and the United States, any more than commercially available wheat cultivars.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Nutritional components of Teal 11A wheat were measured analytically and compared to those of the parental line CDC Teal. These components included: moisture, crude protein, crude fat, crude fibre, the amino acids valine, isoleucine, leucine, threonine, cystine, lysine and methionine. Also measured were fatty acids, B vitamins (thiamine HCL, niacin, pantothenic acid, pyridoxine), and minerals (phosphorus, zinc, magnesium and iron). Other than small but significant differences in crude fibre and oleic acid, which were lower in Teal 11A, there were no differences between Teal 11A and CDC Teal in the levels of all other nutritional components. The nutritional composition of Teal 11A wheat was found to be similar to its nonmodified parent, and within the range of commercial wheat varieties.</p>\n\n<p style="text-align: justify;">The anti-nutrients phytic acid and trypsin inhibitor were measured in Teal 11A and CDC Teal. Phytic acid occurs naturally in wheat and other cereals. It is indigestible by humans and non-ruminant livestock, and inhibits the absorption of iron and other minerals. Trypsin inhibitor interferes with protein digestion. Phytic acid levels in Teal 11A were equivalent to those in CDC Teal. Trypsin inhibitor levels in both Teal 11A and CDC Teal were below the limit of detection.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of Teal 11A wheat was determined by examining the characteristics of the modified AHAS protein and the amino acid sequence homology between the modified protein and known toxins and allergens. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. Data from studies on the heat sensitivity and trypsin degradability of the modified AHAS in Teal 11A showed similar sensitivity to heat and trypsin degradability compared to unmodified AHAS. The unmodified form of AHAS shows no amino acid similarity to known toxins and allergens. The modified AHAS is substantially equivalent to the unmodified enzyme in that it differs by only one amino acid. Evidence was also provided to show that the protein components of Teal 11A were not altered compared to those of unmodified control. Results from HPLC on protein extracts demonstrated that no new major proteins or increased protein expression occurred as a result of the mutation to the AHAS enzyme. From these results it was concluded that Teal 11A wheat did not demonstrate any potential for toxicity and allergenicity compared to conventional unmodified wheat.</p>\n', 'Enabled', NULL, '2013-08-30 00:00:00');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(60, 90, '<p style="text-align: justify;"><b>Dietary exposure</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in AP205CL will not result in any change in the consumption or use pattern of wheat and wheat-based products. The availability of many wheat cultivars for cultivation, the diversity of wheat in phenotypic traits, and the normal variation in wheat composition due to differences in growing conditions all result in a wide variation in the composition of conventional wheat grain. Since the modification to the AHAS enzyme would not be expected to change the gluten content in AP205CL, the cultivation and use of this wheat would not result in any new or additional concern for individuals with celiac disease. Thus, the cultivation of AP205CL would not be expected to change the dietary exposure in Canada and the United States, any more than commercially available wheat cultivars.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Nutritional components of AP205CL wheat were measured analytically and compared to those of the parental line Gunner. These components included: moisture, crude protein, crude fat, crude fibre, the amino acids valine, isoleucine, leucine, threonine, cystine, lysine and methionine. Also measured were fatty acids, B vitamins (thiamine, niacin, pantothenic acid, pyridoxine), vitamin E, and minerals (phosphorus, zinc, magnesium and iron). Significant differences were observed in the levels of palmitic and oleic acid, between AP205CL and Gunner, but these differences fell in the range of conventional wheat varieties. A small but significant difference in the concentration of thiamine was observed between AP205CL and Gunner, the slight difference was not expected to impact on livestock nutrition. There were no other observed differences in nutritional composition.</p>\n\n<p style="text-align: justify;">The anti-nutrients phytic acid and trypsin inhibitor were measured in AP205CL and Gunner. Phytic acid occurs naturally in wheat and other cereals. It is indigestible by humans and non-ruminant livestock, and inhibits the absorption of iron and other minerals. Trypsin inhibitor interferes with protein digestion. Phytic acid levels in AP205CL were not different from those of Gunner and levels of trypsin in both lines were below the limit of detection.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of AP250CL wheat was determined by examining the characteristics of the modified AHAS protein and the amino acid sequence homology between the modified protein and known toxins and allergens. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. Data from studies on the heat sensitivity and trypsin degradability of the modified AHAS in AP250CL showed similar sensitivity to heat and trypsin degradability compared to unmodified AHAS. The unmodified form of AHAS shows no amino acid similarity to known toxins and allergens. The modified AHAS is substantially equivalent to the unmodified enzyme in that it differs by only one amino acid. Evidence was also provided to show that the protein components of AP205CL were not altered compared to those of unmodified control. Results from HPLC on protein extracts demonstrated that no new major proteins or increased protein expression occurred as a result of the mutation to the AHAS enzyme. From these results it was concluded that AP250CL wheat did not demonstrate any potential for toxicity and allergenicity compared to conventional unmodified wheat.</p>\n', 'Enabled', NULL, '2013-08-30 00:03:13'),
(61, 79, '<p style="text-align: justify;"><b>Dietary exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification of MON 71800 spring wheat will not result in any change in the consumption pattern of wheat and wheat-based products. MON 71800 is expected to be used in similar applications as other spring wheat cultivars by the food industry. MON 71800 did not express any novel compositional characteristics, as confirmed by the similarity in composition of the modified line to its parental counterpart, and other conventional spring wheat varieties. Furthermore, the availability of many spring wheat cultivars for cultivation, and the normal variation in wheat composition due to differences in grade and growing conditions, result in a wide variation in the composition of conventional wheat grain. Consequently, the dietary exposure of consumers in the United States to MON 71800 is anticipated to be the same as for other varieties of commercially available spring wheat.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The nutritional components of MON 71800 grain and forage were determined analytically and compared to those of the parental line &lsquo;Bobwhite&rsquo; and several commercial varieties grown at five locations in the United States and Canada. For the grain, these components included proximates (crude protein, crude fat, ash, moisture, total carbohydrates), total dietary fibre, sugars, starch, amino acids, fatty acids, B vitamins, vitamin E and minerals. Forage samples were analyzed for proximates, acid detergent fibre, neutral detergent fibre, calcium and phosphorus. At some of the locations, for both the grain and the forage, there were statistically significant differences in the levels of certain components between MON 71800 and its parental line. These differences within locations could be attributed to environmental effects rather than to any unintended effect of the genetic modification in MON 71800. However, the combined data from all test locations demonstrated that the nutritional composition of MON 71800 grain and forage was comparable to that of the parental line &lsquo;Bobwhite,&rsquo; and other commercial spring wheat varieties.<br />\nPhytic acid occurs naturally in wheat and other cereals. It is indigestible by humans and non-ruminant livestock, and inhibits the absorption of iron and other minerals. Grain samples of MON 71800, the parental line &lsquo;Bobwhite,&rsquo; other commercial wheat varieties were analyzed to determine levels of phytic acid. The concentration of phytic acid in MON 71800 was comparable to that in the parental line, and was within the range of values determined for the commercial varieties and those found in the literature.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of MON 71800 wheat was investigated using the following data and information: results from the determination of amino acid sequence similarity between the CP4 EPSPS proteins and known toxins and allergens; analysis for possible glycosylation of the CP4 EPSPS proteins; analysis of the stability the novel proteins in simulated gastric fluids; results from an acute oral toxicity study in mice using the CP4 EPSPS proteins; and, information on the safety of the <i>cp4 epsps</i> gene donor, <i>A. tumefaciens</i> strain CP4. The potential for increased allergenicity of the grain from MON 71800 was investigated, specifically with regard to endogenous wheat allergens that induce an IgE reaction in susceptible humans. Various immunilogical assays, using sera from humans with an IgE-mediated wheat allergy, were performed with extracts from MON 71800, the parental line, and several other commercial wheat varieties. The possibility that the genetic modification would have also altered the levels of gliadin, proteins that cause celiac enteropathy in susceptible persons, was also investigated. Gliadin levels were measured, and gluten levels calculated in MON 71800, its parental line, and other commercial varieties.</p>\n\n<p style="text-align: justify;">The CP4 EPSPS proteins in MON 71800 showed no amino acid sequence similarity with known toxins and allergens and neither of the two forms of the protein are glycosylated. Both forms of the CP4 EPSPS protein were rapidly digested under simulated gastric fluid conditions, and the enzyme activity of each protein was substantially diminished within the same period as for the digestion. The results of the acute oral toxicity study on mice, at the highest administered dose, showed no adverse effects of the CP4 EPSPS proteins. Gluten levels were not significantly altered by the genetic modification of MON 71800, neither were the endogenous allergens, as demonstrated by the results of the immunological studies.</p>\n\n<p style="text-align: justify;">Both forms of the CP4 EPSPS protein were expressed at very low levels in MON 71800 grain and forage. This fact, along with negative results of the various safety studies, sequence homology investigations, and immunological assays led to the conclusion that MON 71800 spring wheat did not demonstrate any potential for toxicity and novel allergenicity, nor any altered endogenous allergenicity, compared to conventional spring wheat varieties.</p>\n', 'Enabled', NULL, '2013-08-29 23:50:33'),
(62, 93, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification of 3006-210-23 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 line 3006-210-23 to null plants and conventional cotton cultivars. Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. There were no detectable proteins in the oil from line 3006-210-23. Processed linters are composed of pure (&gt;99%) cellulose and are treated with heat and solvent that would be expected to remove and destroy any residual protein.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The nutritional components of 3006-210-23 cottonseed, kernels, toasted meal, hulls and oil were determined analytically and compared to those of the non-transgenic control (a null segregant resulting from several backcrosses of 3006-210-23 with both parental lines). Cottonseed analysis included proximates (crude protein, crude fibre, acid detergent fibre, neutral detergent fibre, total fat, ash, and moisture), minerals, amino acids, and fatty acids, and anti-nutrients (cyclopropenoid fatty acids, gossypol [total and free], aflatoxins). Oil analysis included crude fat, crude protein, moisture, fatty acids, anti-nutrients and anti-oxidants. Kernels, toasted meal, hulls were analyzed as appropriate for the particular fraction. Other than small differences in the levels of some components in cotton seed, which were determined to be biologically insignificant, and most likely due to genotypic and environmental effects, the analyses demonstrated that the composition of 3006-210-23 cottonseed is comparable to that of the non-transgenic control, and seed of other commercial cotton varieties. The composition of cottonseed oil was also comparable to the non-transgenic control and commercial cottonseed oil. Anti-nutrient levels in 3006-210-23 were similar to those of the non-transgenic control and to values published in the literature.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of the Cry1Ac and PAT proteins in line 3006-210-23 was assessed from the following data and information: results of searches for amino acid sequence similarity between the Cry1Ac and PAT proteins and known toxins and allergens; analysis for possible glycosylation of Cry1Ac; in-vitro digestibility studies using simulated gastric fluid; assessment of heat stability; and acute oral toxicity studies with mice.</p>\n\n<p style="text-align: justify;">Both the Cry1Ac and PAT proteins showed no amino acid sequence similarity to known allergens. Both of these proteins were degraded within one minute of exposure to simulated gastric fluid and were no longer detectable by either SDS-PAGE or Western blot analysis. The Cry1Ac protein was no longer biologically active after exposure to temperatures greater than 75&deg;C. No post-translational glycosylation was detected in cotton-expressed Cry1Ac protein. Levels of natural toxicants in cotton (<i>e.g.</i>, gossypol) were not significantly different in 3006-210-23 cotton compared to the non-transgenic control and conventional cotton varieties.</p>\n\n<p style="text-align: justify;">Results of feeding studies on mammals, birds, soil invertebrates, aquatic organisms, and non-target insects showed no observable adverse effects of either the microbially expressed Cry1Ac or the protein expressed in cotton tissues. Generally, for most of the species tested, there was at least 5-fold safety margin between the lowest observed effect level and the highest estimated concentration to which these species might be exposed. A 2-fold safety margin was determined for green lacewing. An additional non-target insect feeding study was requested by the Environmental Protection Agency (EPA) of the United States as a condition of registration. This study was conducted with the minute pirate bug, an important predatory insect found in cotton fields.</p>\n\n<p style="text-align: justify;">Cry proteins in <i>Bt</i> biopesticide formulations have a long history of safe use, with no evidence of adverse effects, other than insecticidal activity towards lepidopteran insect pests. The Cry1Ac protein also was expressed at very low levels in the various tissues of 3006-210-23 cotton. On the basis this information, and the results of the various safety studies and sequence homology investigations, a determination was made that 3006-210-23 cotton did not demonstrate potential for toxicity or allergenicity compared to conventional cotton varieties.</p>\n', 'Enabled', NULL, '2013-08-30 00:08:14'),
(63, 94, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Sugar beet intended for human consumption is generally converted directly to refined white sugar through extensive purification processes. The levels of CP4 EPSPS protein introduced into H7-1 sugar beet were not measured in refined sugar. CP4 EPSPS was expressed at very low levels in the roots, and since refined sugar does not contain detectable levels of protein, there would be virtually no human exposure to CP4 EPSPS. Consequently, there is no anticipated human exposure to this protein as a result of consumption of refined sugar derived from H7-1 sugar beet.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">Detailed analyses conducted over multiple years and environments were carried out to establish the nutritional composition of H7-1 sugar beet. Analyses included crude ash, crude fibre, crude fat, crude protein, carbohydrate (by calculation), dry matter, acid detergent fibre and neutral detergent fibre in both tops and processed roots (brei). Additional quality components were measured in brei including, invert sugar content, polarization (% sucrose), sodium, potassium and alpha-amino nitrogen. No biologically meaningful differences in any compositional and quality parameters were identified between H7-1 sugar beet and the non-transgenic controls. It was concluded that H7-1 sugar beet is equivalent to other commercially available sugar beet with respect to composition and nutritional quality.<br />\nThe presence of naturally occurring toxins and allergens in glyphosate-tolerant sugar beet line H7-1 was investigated. Saponins are the only known toxicants found in sugar beet and are actively eliminated in sugar processing. These are also considered antinutrients; feed intake is reduced due to the bitter taste imparted by these compounds. Saponins were quantified in tops and root and compared to the non-transgenic control. Levels of saponin in H7-1 did not differ significantly from those of the control lines, and were within the range observed for conventional sugar beet cultivars.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of the CP4 EPSPS protein in H7-1 sugar beet was assessed. An amino acid sequence homology search, using the ALLPEPTIDES database, revealed no similarities between CP4 EPSPS and known toxins. A sequence homology search conducted using the ALLERGEN3 database also revealed no similarities between the novel protein and known allergens, including gliadin. The CP4 EPSPS protein was degraded within one minute of exposure to simulated gastric and intestinal fluids, and the enzymatic activity reduced to less than 10% of the initial activity within 15 seconds of exposure. No adverse effects were observed in an acute toxicity study where mice were fed (by gavage) doses of CP4 EPSPS up to 572 mg/kg.</p>\n\n<p style="text-align: justify;">The results of the digestibility and acute oral toxicity studies, sequence homology searches, and the very low expression levels of the novel protein in roots (1.44% of total protein) support the conclusion that the H7-1 is neither toxic nor allergenic, and is as safe as conventional sugar beet varieties.</p>\n', 'Enabled', NULL, '2013-08-30 00:09:52'),
(64, 78, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from TC-6275 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids, such as TC-6275, will not be different from that for other commercially available field maize varieties.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Forage and grain from TC-6275 maize were analyzed for nutritional composition and compared to the nutritional composition of the non-transgenic control (the near-isoline CHPH09B/2MW). In forage, harvested at the dough (R4) stage, there were no significant differences in the mean levels of protein, acid detergent fibre (ADF), neutral detergent fibre (NDF), and phosphorus between TC-6275 and the non-transgenic control line. The mean level of fat in TC-6275 was lower than the control line, but was within the range of values reported in the scientific literature. Conversely, the mean levels of ash, carbohydrate and calcium in TC-6275 were greater than those of the control line, but were also within the range of values reported in the literature.</p>\n\n<p style="text-align: justify;">Grain from TC-6275 and the control line were analyzed for levels of proximates (fat, protein, crude fibre, ADF, NDF, ash and carbohydrates), fatty acids, amino acids, minerals, and vitamins A, B1, B2 and folic acid. TC-6275 was found to have lower levels of crude fibre, ADF, linoleic acid, lysine, calcium, zinc, vitamin B1 and folic acid, while levels of oleic acid, isoleucine, arginine, glutamic acid, praline, iron, vitamin A and E were higher compared to the control line. Although differences were noted, these values remained within the normal range of variation reported for maize grain, with the exception of vitamin A. The levels of vitamin A were higher than the range of values reported in the literature; however, this discrepancy was attributed to different assay methods, rather than genotype.</p>\n\n<p style="text-align: justify;">The levels of the antinutritional compounds phytic acid and trypsin inhibitor were analyzed in TC-6275 and the control line. Statistically significant differences in the levels of these compounds were observed: levels of phytic acid were greater, and those of trypsin inhibitor were less compared to the control line. However, theses differences were within the range reported in the literature for conventional maize lines.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The Cry1F protein expressed in TC-6275 is similar, in biochemical properties and biological activity to that expressed by the maize line TC1507. This was substantiated by data, provided by Dow Agro Sciences, to demonstrate the equivalency in terms of biochemical properties and biological activity, of Cry1F in TC-6275 to that in TC1507. The following are results from investigations on the potential for toxicity and allergenicity of Cry1F expressed maize in TC1507.</p>\n\n<p style="text-align: justify;">The amino acid sequence of Cry1F was compared to the sequences of known toxins and allergens using public protein sequence databases. The amino acid sequence of Cry1F was not homologous with any known toxin or allergen. Results from in vitro digestibility studies using simulated gastric fluids demonstrated rapid digestion of Cry1F: 98% of the protein was degraded within half a minute, and complete digestion was observed in less than 5 minutes. Cry1F is heat labile, as demonstrated by the loss of activity to neonate tobacco budworm after 30 minutes at 75C. The mammalian toxicity of the Cry1F protein was evaluated from results of an acute oral toxicity study. Mice were fed a dose of Cry1F (576 mg/kg body weight) which was well above the highest measured expression level in TC6275 grain (<i>i.e. </i>, 1.68 mg/kg). No toxic effects were observed in the mice when fed at this dose, which was estimated to be 26,000-fold greater to what humans would be exposed based on the typical consumption of foods derived from TC-6275 maize grain.</p>\n\n<p style="text-align: justify;">The PAT protein in TC-6275 was also evaluated for its potential for toxicity and allergenicity. An amino acid sequence homology search no similarity to known toxins and allergens. Results of previous in vitro digestibility studies on the PAT protein demonstrated its rapid digestibility in simulated gastric fluids. These results, and those of other studies previously submitted to regulatory authorities in support of the safety of PAT, substantiate its low potential for toxicity and allergenicity.</p>\n', 'Enabled', NULL, '2013-08-29 23:49:24'),
(65, 89, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in RH44 will not result in any change in the consumption pattern of lentil. The availability of many lentil varieties for cultivation, the diversity of lentil varieties in phenotypic traits, and the normal variation in lentil composition due to differences in growing conditions, all result in a wide variation in the composition of conventional lentil. Thus, the cultivation of RH44 would not be expected to change the dietary exposure to humans, any more than do commercially available lentil cultivars.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">Nutritional components of line RH44 were measured analytically and compared to those of unmodified commercial lentil cultivars. These components included proximates (crude protein, crude fat, crude fibre, ash, moisture), amino acids, fatty acids, vitamins (thiamine, niacin, pantothenic acid, B6), and minerals (magnesium, zinc, iron, phosphorus). The levels of these nutrients in RH44 lentil were within the range observed for currently registered commercial cultivars in Canada. The levels of the antinutritional factors phytic acid and trypsin inhibitor for RH44 were also within the range observed in these commercial cultivars.</p>\n\n<p style="text-align: justify;">Certain components were not included in the compositional analysis of RH44 lentil. These were folacin, riboflavin, vitamin C, copper, potassium and manganese, and lectin. The developer of RH44 provided a rationale to the reviewing regulatory agencies stating that since the overall composition, physiology and phenological characteristics of RH44 were not significantly changed, there was no indication that the levels of these other nutritional components and antinutrients would be outside of the acceptable range for conventional lentil cultivars. The lentil line RH44 is also not intended as a stand-alone cultivar, but rather as genetic stock (and source of the imidazolinone-tolerance trait) for lentil cultivar improvement.</p>\n\n<p style="text-align: justify;">The results of these compositional analyses, and the submitted rationale, led to the conclusion that the lentil line RH44, and any progeny containing its imidazolinone-tolerance trait, would not be nutritionally or compositionally different than conventional commercial lentil cultivars.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of RH44 was investigated by examining the amino acid sequence homology and the characteristics of the altered AHAS protein. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. The AHAS from RH44 demonstrated no enzyme activity after 1 min of heating at 100&ordm;C. The modified AHAS was also completely degraded after 30 minutes of treatment with trypsin, to simulate gastric digestibilitiy. The unmodified form of AHAS demonstrated no amino acid similarity to known toxins or allergens. The amino acid sequence of the mutated AHAS differs by only one amino acid compared to unmodified rice.</p>\n\n<p style="text-align: justify;">The potential for increased allergenicity of the seed from RH44 was investigated, specifically with regard to endogenous lentil allergens that induce an IgE reaction in susceptible humans. The data submitted showed that protein banding patterns and IgE activity from sera obtained from lentil allergic persons were similar among RH44 lentil and the conventional lentil cultivars.</p>\n\n<p style="text-align: justify;">The results of the amino acid sequence homology investigations, heat sensitivity and digestibility studies, and immunological assays led to the conclusion that the lentil line RH44 did not demonstrate any potential for toxicity and novel allergenicity, or any altered endogenous allergenicity, compared to conventional lentil culivars.</p>\n', 'Enabled', NULL, '2013-08-30 00:01:34'),
(66, 80, '<p style="text-align: justify;"><b>Dietary exposure</b></p>\n\n<p style="text-align: justify;">ASR368 creeping bentgrass is intended solely for the production of turfgrass in golf courses, and is not expected to be grown as forage. Some of the vegetation left over from seed production could be used as animal feed. The use of this forage would be very limited, however, since the nutritional value is very poor at such an advanced growth stage.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The nutritional components of ASR368 forage were determined analytically and compared to those of the parental line B99061R, and seven commercial creeping bentgrass cultivars, grown at four locations. Forage samples were analyzed for proximates (crude protein, crude fat, crude fibre, ash, and moisture), acid detergent fibre, neutral detergent fibre, and minerals (calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium and zinc). No significant differences in any of the nutritional parameters were found between ASR368, the parental line, and the conventional cultivars, when averaged over all locations. There were significantly higher levels of moisture and phosphorus at two sites, and significantly lower levels neutral detergent fibre at another site, for ASR368 compared to its parental line. These differences would be attributable to location rather than genotype effects. Overall, the values of the nutritional components in ASR368 were within the range determined for the commercial cultivars</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of the novel protein CP4 EPSPS in ASR368 was investigated using the following data and information: the history of safe consumption of this protein by humans and animals; results from the determination of amino acid sequence similarity between the CP4 EPSPS protein and known toxins and allergens; analysis of the stability the novel protein in simulated gastric fluids; results from an acute oral toxicity study in mice fed CP4 EPSPS protein.</p>\n\n<p style="text-align: justify;">The results of database searches for amino acid sequence similarity between CP4 EPSPS and known toxins and allergens were negative; CP4EPSPS was rapidly digested under simulated gastric fluid conditions; and no adverse effects were observed when mice were fed the highest dose in acute oral toxicity studies. The results of these studies, along with history of safe consumption of CP4 EPSPS, led to the conclusion that ASR368 is not more toxic or allergenic than conventional creeping bentgrass cultivars.</p>\n', 'Enabled', NULL, '2013-08-29 23:51:40'),
(67, 95, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from DAS-59122-7 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids will not be different from that for other commercially available field maize varieties.</p>\n\n<p style="text-align: justify;">The highest levels of expression of Cry34Ab1 and Cry35Ab1 in the grain of DAS-59122-7 were measured to be 117 mg/kg and 1.83 mg/kg, respectively. The actual exposure in the diet is expected to be lower than this due to a number of factors including protein degredation during transport, storage and processing of the grain. The level of PAT expressed in the grain was below the limit of quantitation for this protein (0.06 mg/kg).</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The acute oral toxicity of the two Cry proteins was studied, both individually and combined, using single dose studies in mice. The mice received either a single dose of 2700 mg/kg bw Cry34Ab1, 1850 mg/kg bw Cry35Ab1 or 482 mg/kg bw Cry34Ab1 and 1520 mg/kg bw Cry35Ab1 together, and observed for two weeks. Apart from some fluctuations in body weights common in large dose oral gavage studies, there were no clinical signs noted during the study. All mice survived the observation period and there were no gross pathological changes noted upon post mortem examination of the mice.</p>\n\n<p style="text-align: justify;">Extensive animal testing has shown that the PAT protein is non-toxic to humans and animals and this gene has been expressed in other transgenic crops approved in a number of countries. An acute oral toxicity study with 5000 mg/kg bw of the PAT protein showed no effects in mice.</p>\n\n<p style="text-align: justify;">The protein concentrations tested were orders of magnitude greater than the dose range for this endpoint typically associated with protein toxins. Additionally the PAT protein present in this corn has been extensively studied and has been found safe for consumption in food or feed according to a consensus document concerning the genes and associated enzymes that confer tolerance to phosphinothricin herbicide (OECD, 1999).</p>\n\n<p style="text-align: justify;">Based on the expression levels of these proteins in grain and dietary intake data, exposure to these proteins would be extremely low. The novel proteins were not homologous to known food allergens, as established by amino acid sequence comparisons with allergenic proteins from extensive computerized databases. In digestibility studies using simulated mammalian gastric fluid, the novel proteins were more rapidly digested than non-allergen protein controls. The Cry34Ab1 and Cry35Ab1 proteins are completely inactivated by exposure for 30 min to 90&ordm;C and 60&ordm;C respectively, indicating that both proteins are heat labile. Based on the preceding evidence, the novel proteins expressed in this corn line do not share characteristics of known food allergens.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">Forage and grain from DAS-59122-7 maize, grown at three locations, were analyzed for nutritional composition and compared to a non-transgenic maize control which was derived from the parental line Hi-II, and to published literature values. Samples for analysis were collected from field trials grown at six different locations.</p>\n\n<p style="text-align: justify;">Forage was harvested at the dough stage (R4) and was analyzed for proximates (crude protein, crude fat, moisture, ash, carbohydrate, acid detergent fibre (ADF), neutral detergent fibre (NDF)), and minerals (calcium and phosphorus). No significant differences in the levels crude protein, crude fat, crude fibre, ADF and NDF were observed between DAS-59122-7 and the non-transgenic control. While significant differences were observed in the levels of ash, carbohydrates, calcium and phosphorus, these values were within the ranges reported in the literature for conventional maize hybrids.</p>\n\n<p style="text-align: justify;">Grain samples were obtained from mature (growth stage R6) plants and analyzed for the several components, including proximates (crude protein, crude fat, moisture, ash, carbohydrate, acid detergent fibre and neutral detergent fibre); minerals (calcium, phosphorus, magnesium, copper, iron, manganese, potassium, sodium, and zinc); amino acids; fatty acids; vitamins (A, B1, B2, folic acid, E ); anti-nutrients (phytic acid, trypsin inhibitor, raffinose); and secondary metabolites (ferulic acid, <i>p</i>-coumaric acid, furfural).</p>\n\n<p style="text-align: justify;">Statistical analysis of the mean levels of proximates across all locations revealed no significant differences between DAS-59122-7 and the non-transgenic control, with the exception of crude protein, ash, and carbohydrates. The levels of crude protein and ash were higher, and carbohydrate levels were lower in DAS-59122-7 compared to the control line. Statistically significant differences were reported in the mean levels of most of the fatty acids measured. The levels of linoleic and linolenic acid were higher, while palmitic and stearic acid levels were lower in DAS-59122-7 compared to the control. No significant differences were observed in the levels of oleic acid. The levels of nine of the amino acids measure, <i>i.e.</i>, tryptophan, isoleucine, histidine, valine, leucine, arginine, phenylalanine, proline and tyrosine, were higher in DAS-59122-7 compared to the control. No significant differences were observed in the levels of minerals, except for calcium, which was higher in the transgenic line. Statistically significant differences were observed in the levels folic acid and vitamin E. Despite all of the observed statistically significant differences between DAS-59122-7 and the non-transgenic control, all of the nutritional component values were within the ranges reported in the literature for conventional maize hybrids.</p>\n\n<p style="text-align: justify;">The levels of the antinutritional compounds phytic acid, trypsin inhibitor and raffinose, as well as the secondary metabolites ferulic acid, <i>p</i>-coumaric acid, and furfural were determined in the grain. Phytic acid occurs naturally in maize and other cereals. It is indigestible by humans and non-ruminant livestock, and inhibits the absorption of iron and other minerals. Trypsin inhibitor interferes with enzymes involved in protein digestion. Raffinose is an oligosaccharide found in cereals and legumes which is indigestible in humans and monogastric livestock, thereby limiting the amount of metabolizable engery in foods and feeds. Ferulic acid and <i>p</i>-coumaric acid are compounds which become covalently linked to hemicelluloses during cell wall development. In ruminants, these compounds inhibit cell wall degradation by rumen microorganisms. Furfural is an aromatic aldehyde which can result from the dehydration of pentose sugars in cereals. No significant differences were observed in the levels of these antinutrients, and the secondary metabolites ferulic acid and <i>p</i>-coumaric acid, between DAS-59122-7 and the non-transgenic control maize line. Furfural was not detected in any of the samples analyzed.</p>\n\n<p style="text-align: justify;">The results of these compositional analyses led to the conclusion that DAS-59122-7 forage and grain is not different in nutritional and antinutritional composition compared to maize hybrids currently marketed, grown and consumed.<br />\nNo introduced health concerns would be expected to be associated with the consumption of corn event DAS-59122-7 compared with its non-transgenic parent. DAS-59122-7 corn is deemed to be similar to the non-transgenic parental strain of corn in terms of being an acceptable food source.</p>\n', 'Enabled', NULL, '2013-08-30 00:11:55'),
(68, 96, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from MON88017 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids will not be different from that for other commercially available field maize varieties.</p>\n\n<p style="text-align: justify;"><b>Potential toxicity and allergenicity</b></p>\n\n<p style="text-align: justify;">The two novel proteins present in MON88017 corn have been assessed previously for safety; the CP4 EPSPS protein is present in approved lines of canola, cotton, soybean, potato and other corn events. Previous assessments have shown that CP4 EPSPS administered directly to animals at a high dose is not toxic, and the evidence indicates no potential for this protein to be allergenic in humans. Given its widespread use in approved glyphosate-tolerant crops, it now has a history of safe use in food over 10 years.</p>\n\n<p style="text-align: justify;">In considering the potential toxicity and allergenicity of the Cry3Bb1 variant protein, it is worth noting that Bt formulations containing Cry3Bb1 have been used safely in agriculture since 1995. Two separate acute toxicity studies in mice using the individual Cry3Bb1 variant proteins present in MON88017 and MON863 respectively confirmed the absence of mammalian toxicity in each case. Bioinformatic studies confirmed the absence of any significant amino acid similarity with known protein toxins and allergens, and <i>in vitro</i> digestibility studies demonstrated that Cry3Bb1 variants are rapidly degraded in the stomach following ingestion. Furthermore, processing involving heat treatment renders the Cry3Bb1 variant protein non-functional (i.e. unable to exert a toxic effect in insects). This weight of evidence indicates that the Cry3Bb1 variant protein is not toxic and is unlikely to pose an allergenic risk to humans.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">Forage and grain from MON 88017 maize, grown at three locations, were analyzed for nutritional composition and compared to that of a non-transgenic maize of similar genetic background (<i>i.e.</i>, the conventional maize control), and to the composition of twelve conventional maize hybrids.</p>\n\n<p style="text-align: justify;">Forage was harvested at the late dough to early dent stages and was analyzed for proximates (crude protein, crude fat, moisture, ash and carbohydrate), acid detergent fibre, neutral detergent fibre, calcium and phosphorus. No significant differences in the levels of these components were observed between MON88017, the conventional control and the conventional hybrids.</p>\n\n<p style="text-align: justify;">Grain samples were obtained from mature (growth stage R6) plants harvested at three locations. The levels of several nutritional components were determined, including: proximates (crude protein, crude fat, moisture, ash, and carbohydrate); acid detergent fibre, neutral detergent fibre, total dietary fibre; minerals (calcium, phosphorus, magnesium, copper, iron, manganese, potassium, and zinc); amino acids; fatty acids; vitamins (folic acid, niacin, B1, B2, B6, and E); anti-nutrients (phytic acid, raffinose); and secondary metabolites (ferulic acid, p-coumaric acid).</p>\n\n<p style="text-align: justify;">Statistical analysis of the nutritional component data across all locations revealed no significant differences among MON 88017, the non-transgenic control, and the commercial hybrids, with the exception of levels of vitamin B1, and linolenic and arachidic acid, expressed as percentages of total fatty acids. The differences in linolenic and arachidic acids were not significant when the data was expressed on a dry matter basis. The levels of vitamin B1 were lower in MON 88017 compared to the non-transgenic control, but were within the 99% tolerance interval established using the twelve conventional commercial hybrids.</p>\n\n<p style="text-align: justify;">The levels of the antinutritional compounds phytic acid and raffinose, as well as the secondary metabolites ferulic acid and p-coumaric acid, were determined in the grain. Phytic acid occurs naturally in maize and other cereals. It is indigestible by humans and non-ruminant livestock, and also inhibits the absorption of iron and other minerals. Raffinose is an oligosaccharide found in cereals and legumes. It is cannot be digested by humans and monogastric livestock, thereby reducing the amount of metabolizable energy in foods and livestock feeds. Ferulic acid and p-coumaric acid are phenolic compounds found in cell walls; these become covalently linked to hemicelluloses during cell wall development. In ruminants, these compounds inhibit cell wall degradation by rumen microorganisms. No significant differences were observed in the levels of these antinutrients and secondary metabolites between MON 88017 and the non-transgenic control maize line. The levels of these compounds were also within the 99% tolerance interval established for the twelve conventional maize hybrids.</p>\n\n<p style="text-align: justify;">The results of these compositional analyses led to the conclusion that MON 88017 forage and grain is not different in nutritional and antinutritional composition compared to maize hybrids currently marketed, grown and consumed.</p>\n', 'Enabled', NULL, '2013-08-30 00:15:37');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(69, 97, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification of MON 88913 would not be expected to result in any change in the consumption pattern of cotton products. MON88913 did not express any novel characteristics with regard to the seed and oil that would alter the consumption pattern. This was confirmed by comparison of the levels of proximates, and fatty acids in MON 88913 to the non-transgenic counterpart and to conventional cotton cultivars.</p>\n\n<p style="text-align: justify;">Only refined cottonseed oil and cellulose from processed linters of cottonseed are consumed by humans. Processed linters are composed of pure (&gt;99%) cellulose and are treated with heat and solvent that would be expected to remove and destroy any residual protein. Cottonseed oil for human consumption is highly refined and does not contain detectable levels of protein. Cottonseed oil and linters are therefore not expected to contain any detectable levels of CP4 EPSPS protein.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">The nutritional components of MON 88913 whole delinted cottonseed, cottonseed meal, and refined cottonseed oil were determined analytically and compared to those of the non-transgenic control line, and several commercial cottonseed cultivars grown in replicated field trials at four locations in 2002. The non-transgenic control line consisted of a null segregant containing the same genetic background as MON 88913, with the exception of the transgenes.<br />\nThe analysis of whole delinted (acid-delinted) cottonseed included proximates (crude protein, crude fibre, total fat, ash, moisture, and carbohydrates), acid detergent fibre, neutral detergent fibre, total dietary fibre, amino acids, fatty acids (C8 to C22), minerals (calcium, copper, iron, magnesium, phosphorus, potassium, sodium and zinc), and antinutritional compounds (cyclopropenoid fatty acids, gossypol [total and free], and aflatoxins). A combined statistical analysis across all locations revealed significant differences among the cultivars in the levels of the amino acids phenylalanine and tryptophan, the fatty acids oleic acid and linoleic acid, moisture, and manganese. Phenylalanine, linoleic acid and manganese levels were higher, and tryptophan and oleic acid levels were lower in MON 88913 compared to the non-transgenic control. However, the levels of these nutrients were within the 99% tolerance interval established for the conventional cotton varieties. The moisture levels for MON 88913 were outside of the tolerance interval, but within the range of values in the literature for conventional cotton. Analyses on mechanically-delinted whole cottonseed also revealed significantly higher values of phenylalanine in MON 88913; however, these values were within the range of those in the literature, and within the 99% tolerance for the conventional cultivars.<br />\nThe composition of cottonseed meal was similar to that of whole cottonseed, with the exception of analyses for fatty acids, vitamin E and total dietary fibre. No significant differences were observed in the levels of nutrients between MON 88913 and the non-transgenic control.</p>\n\n<p style="text-align: justify;">The analysis of refined cottonseed oil consisted of fatty acids (C8 to C22), vitamin E, cyclopropenoid fatty acids (malvalic acid, sterculic acid and dihyroterculic acid), and gossypol (free and total). Statistically significant differences were observed between MON 88913 and the non-transgenic control in the levels of the fatty acids myristic acid and behenic acid. The mean levels of these fatty acids were lower in MON 88913, but within the 99% tolerance interval established for the conventional cultivars, and the range of values in the literature. Other than for those specific fatty acids, refined cottonseed oil from MON 88913 was not significantly different in composition compared to oil from conventional cotton.</p>\n\n<p style="text-align: justify;">No significant differences were observed in the levels of antinutritional compounds in whole cottonseed, cottonseed meal and oil, with the exception of gossypol in cottonseed meal. The level of total gossypol were significantly lower in MON 88913 compared to the non-transgenic control, but fell within the range of literature values, and the 99% tolerance interval for conventional cotton.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The toxicity of MON 88913 was assessed by an analysis of the levels of naturally occurring toxins in cotton and, an evaluation of the novel protein CP4 EPSPS. The levels of the toxicants gossypol (free and total) and cyclopropenoid fatty acids (malvalic, sterculic, and dihydrosterculic acid) were quantified in whole delinted cottonseed, cottonseed meal, and cottonseed oil.</p>\n\n<p style="text-align: justify;">Gossypol has numerous toxic effects on mammals, including heart damage and heart failure, such that whole cottonseed or cottonseed meal is not used in human foods, and its use as a monogastric livestock feed is limited. However, the removal or inactivation of gossypol during processing enables the use of some cottonseed meal as feed for poultry, pigs and fish.</p>\n\n<p style="text-align: justify;">Statistically significant differences in the levels of gossypol were observed only in cottonseed meal from MON 88913 and the non-transgenic control. Levels of total gossypol were lower in MON 88913, compared to the non-transgenic control, and were within the range observed in the published literature and in the 99% tolerance interval calculated for several commercial varieties grown at various locations.</p>\n\n<p style="text-align: justify;">The cyclopropenoid fatty acids, sterculic (C-17), dihydrosterculic (C-19) and malvalic (C-18), are naturally found in the seed oil of cotton and other species of the Malvales (<i>e.g.</i>, kapok). These compounds produce undesirable biological effects, including the inhibition of biodesaturation of stearic to oleic acid, which detrimentally affects phospholipid biosynthesis. There were no statistically significant differences observed in the levels of these fatty acids in cottonseed, cottonseed meal or cottonseed oil from MON 88913 and the non-transgenic control.</p>\n\n<p style="text-align: justify;">The potential for toxicity of the CP4 EPSPS was previously tested by acute gavage exposure in mice, and by conducting searches for amino acid sequence homology of the novel protein with those of known toxins. No adverse effects were observed when CP4 EPSPS was administered at levels up to 572 mg/kg of body weight. This dose represented a level of CP4 EPSPS that was 1000-fold the anticipated level that would be consumed in food products. The sequence homology searches were conducted using public protein databases. The results of the searches revealed no biologically relevant sequence similarities between CP4 EPSPS and known toxins.</p>\n\n<p style="text-align: justify;">The CP4 EPSPS was also evaluated for potential allergenicity. An amino acid sequence homology search revealed no similarity to known allergens, including gliadin. Results of previous in vitro digestibility studies on CP4 EPSPS demonstrated its rapid digestibility in simulated gastric and intestinal fluids, which is characteristic of non-allergenic proteins. These results, and those of other studies previously submitted to regulatory authorities in support of the safety of CP4 EPSPS, substantiate its low potential for allergenicity.</p>\n', 'Enabled', NULL, '2013-08-30 00:18:10'),
(70, 109, '<p style="text-align: justify;"><b>Dietary exposure</b></p>\n\n<p style="text-align: justify;">The genetic modification in J101 and J163 will not result in changes in the use of alfalfa as an animal feed. Any cultivars resulting from crosses with either of events J101 or J163 are expected to be used in similar applications as conventional alfalfa cultivars, with the sole exception that these cultivars can only be cultivated as pure stands. In mixed grass-alfalfa stands, the grass portion would be eliminated by the use of glyphosate. The nutritional quality analysis of these alfalfa lines did not reveal any novel compositional characteristics compared to conventional cultivars, and the nutritional composition was within the normal range of variability observed in conventional alfalfa. Furthermore, due to the availability of many alfalfa cultivars adapted to different environmental and management conditions, the dietary exposure of livestock animals to forage from either J101 or J163 alfalfa cultivars is therefore expected to be similar to that of conventional alfalfa.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The nutritional composition of lines J101 and J163 was determined analytically and compared to that of a null segregant control population (from backcrosses with parental populations), and to twelve conventional alfalfa cultivars. Samples were obtained from second cut forage, harvested at early to late bloom, from five locations in the United States. Forage samples were analyzed for 35 nutritional components including proximates (crude protein, fat, ash, and moisture), acid detergent fibre, neutral detergent fibre, amino acids, and nine minerals, including calcium, magnesium, phosphorus and potassium. A 99% tolerance interval for the compositional constituents was developed using the twelve conventional alfalfa cultivars.</p>\n\n<p style="text-align: justify;">Statistically significant differences were observed in the levels of cystine, histidine, lysine, tyrosine, acid detergent fibre, neutral detergent fibre, and lignin in either J101 or J163, compared to the control population. While some of these differences were observed within and among locations, all of the compositional values of J101 and J163 were within the tolerance interval established for each constituent, and were also comparable to published literature values.<br />\nCoumestrol is an antinutritional estrogenic compound found naturally in alfalfa. Forage samples from trials conducted at four locations were analyzed for coumestrol. No significant differences in the levels of coumestrol were observed among lines J101, J163, the control line, and the commercial cultivars.</p>\n\n<p style="text-align: justify;">Results from the nutritional and compositional analyses supported the conclusion that forage from events J101 and J163 is nutritionally comparable to that from currently available commercial cultivars of alfalfa.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of the alfalfa events J101 and J163 was assessed from data and information obtained from previous studies and investigations conducted in support of the safety of CP4 EPSPS, and the gene donor <i>A. tumefaciens</i> strain CP4. Results from these studies and investigations have demonstrated that CP4 EPSPS is functionally equivalent to native EPSPS, except for a reduced affinity for glyphosate; the <i>cp4 epsps</i> gene donor has a history of safe use; CP4 EPSPS is not homologous to known toxins and allergens; the protein it is rapidly digested in simulated gastric fluids; and that no treatment-related adverse effects were observed in acute toxicity tests where mice were fed up to 572 mg of CP4 EPSPS per kg of body weight. The no-observed adverse effects level of 572 mg/kg is approximately 20 times the amount of CP4 EPSPS to which a ruminant animal would be exposed when consuming a typical daily ration of alfalfa forage. The results of these studies and investigations, and data demonstrating the relatively low expression levels of CP4 EPSPS, led to the conclusion that the alfalfa events J101 and J163 are no more toxic or allergenic than conventional alfalfa cultivars.</p>\n', 'Enabled', NULL, '2013-08-30 00:23:03'),
(71, 110, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">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 (&gt;99%) cellulose and are treated with heat and solvent; these processes would be expected to remove and destroy any residual protein.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;">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.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of the novel proteins VIP3A and APH4 was determined from results of acute feeding studies using mice, from <i>in-vitro</i> 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.</p>\n', 'Enabled', NULL, '2013-08-30 00:24:55'),
(72, 131, '<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">Corn line 3272 expresses two novel proteins &ndash; the enzymes AMY797E and PMI. AMY797E is expressed at relatively high levels in grain (838 &ndash;1627 &micro;g/g fresh weight or 1004&ndash;3365 &micro;g/g dry weight) and PMI is expressed at low levels (&lt;0.4&ndash; 0.8 &micro;g/g fresh weight or &lt;0.5&ndash; 1.8 &micro;g/g dry weight). Neither protein showed any evidence of toxicity in acute oral toxicity studies and also do not exhibit any amino acid sequence similarity with known protein toxins. Neither of the proteins is derived from sources known to be allergenic and both are rapidly digested in simulated digestion studies. AMY797E has no immunologically meaningful amino acid sequence similarity to known allergens. PMI was found to share a short sequence of amino acids (eight residues) with a known allergen, however further testing with human sera from allergic individuals did not demonstrate any cross-reactivity. Overall, the evidence indicates that AMY797E and PMI are non-toxic and have limited potential to be allergenic in humans.</p>\n\n<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. Given that the proposed use of this maize event is for the production of ethanol, is unlikely that the co-mingling of corn line 3272 with existing corn stocks will have any significant effect on population nutrition.</p>\n\n<p style="text-align: justify;">As the alpha-amylase enzyme expressed in Event 3272 has the ability to reduce starch molecules into component dextrins and mono/disaccharides at high temperatures, its potential impact on glycemic index, should Event 3272 be used as human food, was evaluated. This evaluation concluded that the co-mingling of Event 3272 with existing corn stocks is unlikely to have any significant effect on population nutrition. It is possible the AMY797E alpha-amylase may be activated during the cooking or processing of products containing Event 3272, which could increase the glycemic index of the final food product. However, even if the final food&rsquo;s glycemic index was increased, the overall effect on the diet would be minimal, given that glycemic index is heavily influenced by other dietary factors.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">Compositional analyses were carried out to establish the nutritional adequacy of grain and forage from Event 3272, in comparison to conventional control lines. The constituents measured in grain from this event were protein, fat, carbohydrate, ash, moisture, fibre, fatty acids, amino acids, vitamins, minerals, secondary metabolites and anti-nutrients. In forage, the constituents measured were protein, carbohydrate, ash, moisture, fibre and minerals.</p>\n\n<p style="text-align: justify;">No compositional differences of biological significance were observed between the Event 3272 grain and forage and its non-GM counterpart. Several minor differences in key nutrients and other constituents were noted however the levels observed represented very minor differences and were within the reference range from conventional varieties. It can be concluded that food and feed from amylase-modified corn line 3272 is equivalent in composition to that from other commercial corn varieties.</p>\n\n<p style="text-align: justify;">A 42-day feeding study in broiler chickens supports this finding, with no evidence of biologically-significant differences in growth or feed conversion in chickens fed Event 3272 grain compared to near-isogenic control or commercially available maize lines.</p>\n', 'Enabled', NULL, '2013-08-30 13:08:48'),
(73, 122, '<p style="text-align: justify;"><b>Dietary exposure:</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in BW255-2 and BW238-3 will not result in any change in the consumption or use pattern of wheat and wheat-based products. The availability of many wheat cultivars for cultivation, the diversity of wheat in phenotypic traits, and the normal variation in wheat composition due to differences in growing conditions all result in a wide variation in the composition of conventional wheat grain. Since the modification to the AHAS enzyme would not be expected to change the gluten content in BW255-2 and BW238-3, the cultivation and use of this wheat would not result in any new or additional concern for individuals with celiac disease. Thus, the cultivation of BW255-2 and BW238-3 would not be expected to change the dietary exposure in Canada and the United States, any more than commercially available wheat cultivars.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data:</b></p>\n\n<p style="text-align: justify;">Nutritional components of BW255-2 and BW238-3 wheat were measured analytically and compared to those of the parental lines. These components included: moisture, crude protein, crude fat, crude fibre, and the amino acids valine, isoleucine, leucine, threonine, cystine, lysine and methionine. Also measured were fatty acids, B vitamins (thiamine, niacin, pantothenic acid, pyridoxine), vitamin E, and minerals (phosphorus, zinc, magnesium and iron). Statistically significant differences were observed in the levels of protein between BW255-2 and BW238-3 and their parental controls. Significant differences were also observed in the concentration of branched-chain amino acids and Vitamin B1 between BW238-3 and its parental control and in Mg, Fe and panthothenic acid between BW255-2 and its parental control. However, the levels of all of these nutritional components fell within the range of conventional wheat varieties supporting the conclusion that the nutritional composition of BW255-2 and BW238-3 is equivalent to conventional bread wheat varieties.</p>\n\n<p style="text-align: justify;">The anti-nutrients phytic acid and trypsin inhibitor were measured in BW255-2 and BW238-3 grain samples. Phytic acid occurs naturally in wheat and other cereals. It is indigestible by humans and non-ruminant livestock, and inhibits the absorption of iron and other minerals. Trypsin inhibitor interferes with protein digestion. Phytic acid levels in BW255-2 and BW238-3 were not significantly different from those of the parental controls and trypsin inhibitor was not detected in events BW255-2 and BW238-3 or their parental controls.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity: </b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of BW255-2 and BW238-3 wheat were determined by examining the characteristics of the modified AHAS protein and the amino acid sequence homology between the modified protein and known toxins and allergens. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. Data from studies on the heat sensitivity and trypsin degradability of the modified AHAS in BW255-2 and BW238-3 showed similar sensitivity to heat and trypsin degradability compared to unmodified AHAS. The unmodified form of AHAS shows no amino acid similarity to known toxins and allergens. The modified AHAS is substantially equivalent to the unmodified enzyme in that it differs by only one amino acid. Evidence was also provided to show that the protein components of BW255-2 and BW238-3 were not altered compared to those of unmodified parental controls. Results from HPLC on protein extracts demonstrated that no new major proteins or increased protein expression occurred as a result of the mutation to the AHAS enzyme. From these results it was concluded that BW255-2 and BW23803 wheat did not demonstrate any potential for toxicity and allergenicity compared to conventional unmodified wheat.</p>\n', 'Enabled', NULL, '2013-08-30 00:41:25'),
(74, 123, '<p style="text-align: justify;"><b>Nutritional Data (Livestock Feed Purposes)</b></p>\n\n<p style="text-align: justify;">Data on fatty acid profiles, protein content, amino acid composition, crude fibre, ash, phytate, and moisture content were provided for grain samples from lines IMINTA 1 and IMINTA 4 and the parental variety IRGA 417 grown in two locations in Argentina. Comparisons of these parameters between the herbicide-tolerant lines and conventional variety revealed some statistically significant differences (lower crude fat and oleic acid levels and lower levels of panthothenic acid), but levels were all within the range for conventional rice varieties.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The single amino acid change within the native ALS enzyme was not anticipated to have any effect on the potential toxicity or allergenicity of this protein. The unmodified form of this enzyme does not display amino acid sequence homology with known protein toxins or allergens. The modified ALS protein from IMINTA 1 and IMINTA 4 was shown to be rapidly inactivated by heat (1 minute at 100&deg;C) and equivalent to the parental controls with respect to trypsin degredation. Susceptibility to heat inactivation and sensitivity to proteolytic degradation are not characteristics of known protein toxins or allergens.</p>\n\n<p style="text-align: justify;">Measurements of the concentrations of normally occurring rice antinutritional factors (<i>e.g.</i>, phytic acid and trypsin inhibitor) did not reveal any differences between these herbicide-tolerant lines and the parental rice variety. For all of the lines, the concentrations of trypsin inhibitor were below the threshold of detection.</p>\n', 'Enabled', NULL, '2013-08-30 00:42:43'),
(75, 111, '<p style="text-align: justify;"><b>Toxicity and Allergenicity:</b></p>\n\n<p style="text-align: justify;">Amino acid sequence alignment analysis, using the FASTA algorithm, revealed 23.9% identity between cDHDPS and <i>Mercurialis annua</i> profilin allergen over a 92 amino acid window. However, the length of the overlap is relatively short when compared to the full length (303 amino acid) cDHDPS protein and the longest stretch of the contiguous amino acid identities consisted of three amino acids. Based on this result, it is considered that cross-reactivity between cDHDPS and <i>M. annua</i> profilin allergen is highly unlikely. No other immunologically relevant sequences were detected when cDHDPS amino acid sequence was compared to the allergen sequences in AD4 database and it was concluded that cDHDPS protein is unlikely to share structurally and immunologically relevant sequence similarities with known allergens.</p>\n\n<p style="text-align: justify;">In <i>in vitro</i> digestion studies, greater than 96% of the cDHDPS protein was digested in simulated gastric fluid within 30 seconds supporting the conclusion that cDHDPS has a low allergenic potential.</p>\n\n<p style="text-align: justify;">An acute high dose oral toxicity study in mice using <i>E. coli</i>-derived cDHDPS protein involving a single gavage dose of 800 mg of cDHDPS/kg body weight did not result in any mortalities or adverse clinical reactions in mice.</p>\n\n<p style="text-align: justify;"><b>Dietary Exposure:</b></p>\n\n<p style="text-align: justify;">The levels of cDHDPS protein in LY038 were evaluated in tissue samples collected from plants grown at five field sites in the U.S., using an ELISA assay with goat polyclonal antibody specific for cDHDPS. The negative segregant LY038(-) was used as the negative control and <i>E. coli</i>-derived cDHDPS as the reference standard. The mean cDHDPS protein levels in LY038 grain, forage in the early dent stage, whole plant, forage root, root, and pollen tissues were 26.0, 0.94, 0.081, 0.069, 1.5, and 0.78 &micro;g/g dry weight, respectively. cDHDPS in leaf tissue was measured at four time points throughout the growing season and was not detected at the assay detection limit of 0.013 &micro;g/g fresh weight. These results indicate that cDHDPS is expressed primarily in the grain tissue as expected from the use of the Glb1 promoter. The estimated potential maximum daily intake of the cDHDPS protein for broilers, young pigs, and finishing pigs was calculated to be 1482, 962, 598 &micro;g/kg BW/day, respectively.</p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. As the target use of LY038 is for animal feed, dietary exposure to humans of the cDHDPS protein will be significantly lower than the estimated levels calculated above for animals fed with this maize.</p>\n\n<p style="text-align: justify;"><b>Lysine Catabolites:</b></p>\n\n<p style="text-align: justify;">The grain of LY038 maize contains elevated levels of lysine and its catabolites saccharopine and ?-aminoadipic acid. Animals are continually exposed to saccharopine and ?-aminoadipic acid in the normal course of endogenous lysine metabolism and these compounds are degraded and ultimately become substrates for the tricarboxylic acid cycle, entering as acetoacetyl-CoA. Even if farm animals consumed large amounts of LY038 maize grain, the saccharopine would be completely degraded because of the excess capacity of saccharopine dehydrogenase in their liver and it would neither cause a safety problem to animals, nor would it accumulate in the tissue to pose a problem to humans consuming meat. Articles in the literature report studies in pigs, rats, and broiler chickens showing no adverse effects when animals were exposed to saccharopine or ?-aminoadipic acid. Furthermore, substantial amounts of ?-aminoadipic acid and saccharopine are found in foods commonly consumed by people. For example, ?-aminoadipic acid is found in lentils, garden peas, broccoli, cauliflower, green beans and lettuce and saccharopine is normally found in asparagus, edible mushrooms, lettuce, lentils and brie cheese.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data:</b></p>\n\n<p style="text-align: justify;">The composition of forage and grain from maize LY038 was evaluated using forage and grain from a negative segregant LY038(-), which did not contain the <i>cordapA</i> gene, as the control material. LY038 and LY038(-) maize lines were grown during the 2002 field season at five replicated fields in a randomized complete block design with three replicates per block. In addition, 20 conventional maize hybrids (reference material) were grown, four per site, to determine the amount of variation in nutrient composition that might be expected at each site. Forage and grain samples were collected from all plots and analyzed for nutritional components, anti-nutrients and secondary metabolites. In addition, six lysine-related secondary metabolites from lysine biosynthetic and catabolic pathways, as well as free (not incorporated into protein) and total lysine, were analyzed in LY038, LY038(-), and the conventional maize hybrid grain samples.</p>\n\n<p style="text-align: justify;">Forage was harvested at the early dent stage. Compositional analyses of the forage revealed no statistically significant differences in the mean levels of all measured components except for phosphorus. The level of phosphorus was lower in LY038 than in LY038(-). However, the levels of all components, including phosphorus, fell within ranges detailed in the literature and within the 99% tolerance interval calculated for the conventional maize hybrids grown as controls.</p>\n\n<p style="text-align: justify;">Grain samples were harvested at maturity (R6 growth stage) and analyzed for 75 components. Analytical data showed that, as intended, the levels of free and total lysine were higher in the LY038 grain than in the control LY038 (-) grain. However, the range of total lysine levels in LY038 was within the range reported for field maize. As expected, the levels of lysine catabolites, (saccharopine and ?-aminoadipic acid) were also elevated in the LY038 grain.</p>\n\n<p style="text-align: justify;">Other statistically significant compositional differences were either within the 99 % tolerance level and/or within historical ranges for maize based on the field studies or ranges reported in the literature. No statistically significant differences were observed between LY038 and LY038(-) in the levels of antinutrients (phytic acid and raffinose) and secondary metabolites (ferulic acid and p-coumaric acid).</p>\n\n<p style="text-align: justify;"><b>Bioefficacy and Safety of LY038 in Broiler Chickens:</b></p>\n\n<p style="text-align: justify;">Maize-based diets for poultry and swine are typically deficient in the amino acid lysine and these diets are commonly supplemented with crystalline lysine to meet the animal&#39;s amino acid requirements. LY038 was developed to provide maize grain with consistently higher lysine content. To assess the nutritional value of the increased level of lysine in LY038, and the wholesomeness of LY038 when used as animal feed, a 42 day feeding study was conducted on growing broiler chickens, the primary intended market for LY038. A statistically significant increase in growth rate and feed efficiency was observed in broilers fed LY038 versus birds fed LY038(-) or four conventional varieties not supplemented with lysine. Chick mortality was low and random without any relationship to treatment. No unexpected effects on bird health were observed with the feeding of LY038 grain.</p>\n', 'Enabled', NULL, '2013-08-30 00:27:10'),
(76, 125, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Estimated levels of potential exposure to the CP4 EPSPS enzyme from MON89788 were calculated using a Dietary Exposure Evaluation Model and food consumption data from the USDA survey of individual food intake. Assuming that all soybean food items consumed were derived from MON89788 soybeans, the 95th percentile for acute dietary intake would be 9.9 &micro;g/kg body weight for adults and 391 &micro;g/kg bodyweight for non-nursing infants. It is considered that the genetic modification of MON89788 soybean will not result in any change in the consumption pattern of soybean products. In particular, over 90% of soybean grown in the United States already contains the same CP4 EPSPS protein present in MON89788, which has been extensively evaluated prior to approval in 1996. Furthermore, experience of safe use has been shown with this protein, which is present in Roundup Ready soybean and corn that has been widely grown around the world for more than ten years. Dietary exposure to EPSPS is not novel in that all plants, bacteria and fungi produce this enzyme and the CP4 EPSPS will be ingested as inactive denatured protein since all soybean-derived human food products are heated prior to consumption.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential for toxicity of the CP4 EPSPS protein from MON89788 was evaluated by examining the amino acid sequence homology to known toxins, acute oral toxicity studies on mice, and the characteristics and source of the protein. The amino acid sequence of CP4 EPSPS was determined to be closely related to the sequence of the endogenous soybean EPSPS enzyme. An analysis of the amino acid sequence of the inserted CP4 EPSPS enzyme did not show homologies with known mammalian protein toxins, contained in a sequence databases TOXIN5, and was not judged to have any potential for human toxicity. Acute oral toxicity studies with purified CP4 EPSPS did not reveal any deleterious effects when mice were administered a dose of 572 mg/kg body weight, which was approximately 1500-fold greater than the 95th percentile for acute dietary intake calculated for non-nursing infants. Furthermore, EPSPS is an enzyme that is ubiquitous in nature, present in plants, fungi and micro-organisms and therefore would not be expected to be toxic or allergenic and the donor organism, <i>Agrobacterium tumefaciens</i> strain CP4 is not a known human or animal pathogen.</p>\n\n<p style="text-align: justify;">A search for amino acid sequence similarity between the CP4 EPSPS protein and known allergens revealed no significant amino acid sequence homologies. In addition, the potential for allergenicity was assessed based upon the characteristics of known food allergens (stability to digestion, stability to processing). Unlike known protein allergens, CP4 EPSPS was rapidly degraded by acid and/or enzymatic hydrolysis when exposed to simulated gastric or intestinal fluids with more than 95% of the protein digestions within 15 seconds in simulated gastric fluids. Overall, the CP4 EPSPS does not possess characteristics typical of known protein allergens and there are no reports of allergy to <i>A. tumefaciens</i> strain CP4, the source of the protein</p>\n\n<p style="text-align: justify;">Soybean is known to contain endogenous allergens which elicit an allergic response in a small number of individuals. To assess whether the transformation process may have increased the overall allergenicity of MON89788 compared to conventional soybean, an IgE-binding ELISA study was conducted. Sera used for the assays was obtained from 16 individuals with IgE-mediated allergy to soy and six non-allergic individuals and the assays were performed with extracts from MON89788, A3244 (the parental non-transgenic line) and 24 commercial soybean varieties. The study showed no greater allergic potential from MON89788 than from the other non-transgenic soybean varieties which are currently all present on the market.</p>\n\n<p style="text-align: justify;"><b>Nutritional Data</b></p>\n\n<p style="text-align: justify;">Compositional analyses were conducted to assess whether the nutrient and anti-nutrient levels in grain and forage tissues derived from MON89788 were comparable to those from A3244, the conventional parental line. An additional 12 conventional soybean varieties were included in the comparison to establish a range of natural variability and define a tolerance interval for each particular analyte. Grain and forage tissues were collected from MON89788 and A3244 grown in three replicated plots at each of five trial sites across the US during 2005.</p>\n\n<p style="text-align: justify;">A total of 42 components were analysed in grain samples, including proximates (protein, fat, ash, fibre and moisture), amino acids, fatty acids, anti-nutrients, isoflavones and vitamins. Statistical significance was declared at the 5% level and the only differences between MON89788 and A3244 grain were in the levels for Vitamin E and the isoflavoes daidzein and glycitein. These differences were small (1.6-11%) and all fell within the 99% tolerance levels established for these parameters calculated from the analysis of the conventional varieties. Forage samples were analysed for proximates and the only significant difference was in moisture level, which once again was within the 99% tolerance interval calculated from the analysis of conventional varieties. From these results it was concluded that MON89788 is compositionally equivalent to conventional soybeans.</p>\n', 'Enabled', NULL, '2013-08-30 00:44:42');
INSERT INTO `gmcropdatabase_events_fsafeties` (`id`, `eventId`, `description`, `status`, `created`, `updated`) VALUES
(77, 113, '<p style="text-align: justify;"><strong>Dietary Exposure</strong></p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients.&nbsp; Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from MIR604 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids will not be different from that for other commercially available field maize varieties.</p>\n\n<p style="text-align: justify;"><strong>Equivalence of Bacterial Expressed Proteins</strong></p>\n\n<p style="text-align: justify;">As it is very difficult to extract and purify sufficient quantities of the subject protein from transgenic corn plants for laboratory studies, it has become standard practice to instead use equivalent proteins that have been produced using bacterial expression systems.&nbsp; mCry3A and PMI were produced in recombinant <em>E. coli</em>, purified and used in laboratory toxicity and allergenicity studies.</p>\n\n<p style="text-align: justify;">Prior to use in these laboratory studies, the bacterially produced proteins are compared to the proteins produced&nbsp;<em>in planta</em> in order to establish their equivalence. The molecular identity and biochemical characteristics of the proteins expressed <em>in planta</em> and in the bacterial-expression systems were examined by analysis of biochemical and functional parameters, including molecular weight determination, immunoreactivity, glycosylation analysis and biological activity.&nbsp; SDS-PAGE and Western blotting confirmed the expected molecular weight of mCry3A to be approximately 67,700 Daltons. In the plant derived protein sample, a second band was present and was thought to represent mCry3A that had been degraded in the plant cell.&nbsp; PMI was confirmed to be approximately 45,000 Daltons.&nbsp; No glycosylation was observed for either protein.</p>\n\n<p style="text-align: justify;">The insecticidal activity of plant-derived mCry3A was similar to the bacterially produced protein and the enzyme activity of plant-derived PMI was equivalent to that of the bacterially produced enzyme.&nbsp; The two amino acid changes in the plant expressed PMI do not affect the function of this enzyme.</p>\n\n<p style="text-align: justify;">These studies established that bacterially produced mCry3A and PMI are equivalent to those proteins produced in corn line MIR604, thus support the use of the bacterial proteins in the toxicity testing.</p>\n\n<p style="text-align: justify;"><strong>Toxicity</strong></p>\n\n<p style="text-align: justify;">The mCry3A protein extracted and purified from the recombinant <em>E. coli</em> was used as the test material for an acute oral toxicity study with mice.&nbsp; The mice received a single dose of 2377 mg/kg bw mCry3A and were observed for two weeks.&nbsp; Parameters evaluated included body weights, food consumption and detailed clinical observations. At the end of the study all animals were killed and examined post mortem.&nbsp; Brain, liver, kidneys and spleen were weighed and selected tissues were taken for histopathological examination.</p>\n\n<p style="text-align: justify;">One female mouse was killed on day 2 of the study due to clinical signs consistent with a dosing injury and not related to the test substance.&nbsp; No test substance-related mortalities occurred.&nbsp; There were no test substance-related effects on body weight, food consumption, organ weights or macroscopic and microscopic pathology.&nbsp; Therefore, under the conditions of this study, the acute oral LD50 of mcry3A in mice is greater than 2377 mg/kg bw, the highest dose tested</p>\n\n<p style="text-align: justify;">For PMI, the mice received a single dose of 3080 mg/kg bw of the bacterially expressed protein and were observed for two weeks.&nbsp; Parameters evaluated included body weights and detailed clinical observations. At the end of the study all animals were killed and examined post mortem.&nbsp; Brain, liver, kidneys and spleen were weighed.</p>\n\n<p style="text-align: justify;">One male in the control group and two in the test group died shortly after dosing or were in distress after dosing and subsequently died.&nbsp; Necropsy revealed perforated oesophagi in these animals, a sign of gavage error and not test-substance related.&nbsp; One replacement animal was available for each group and dosed in the same manner on day 0.&nbsp; There was no test article related mortality during the study.&nbsp; No clinical signs of toxicity were observed in either group.&nbsp; There were no test-substance related effects on body weight, organ weights or gross pathology.&nbsp; Under the conditions of this study, the acute oral LD50 of the PMI protein in mice is greater than 3080 mg /kg bw.</p>\n\n<p style="text-align: justify;">To determine whether mCry3A has any significant homology with known protein toxins, its amino acid sequence was systematically compared to the latest posting of the National Centre for Biotechnology Information Entrez Protein Database containing all the publicly available protein sequences.&nbsp; The appropriate cut-off expectation (E) value was determined to be 0.38 and amino acid sequences with E values lower than this were considered to be significant.</p>\n\n<p style="text-align: justify;">Two hundred and twenty three entries in GenBank returned E values below 0.38.&nbsp; Most of these (216) were identified as known or putative delta-endotoxins&nbsp; with a similar function to mCry3A.&nbsp; None of other entries were identified as known or putative toxins other than delta-endotoxins.</p>\n\n<p style="text-align: justify;">To determine whether the PMI protein sequence has any significant homology with known protein toxins, it was compared to known protein sequences in a similar manner.&nbsp; The sequence used in this study did not take into account the two amino acid changes present in PMI in MIR604.&nbsp; The appropriate cut-off expectation (E) value was determined to be 0.17 and amino acid sequences with E values lower than this were considered to be significant.</p>\n\n<p style="text-align: justify;">One hundred and thirty three protein entries in GenBank returned E values below 0.17. One hundred and fourteen of these were identified as known or putative PMI proteins.&nbsp; Sixteen entries were hypothetical proteins and 3 were unnamed proteins.&nbsp; No association with known or putative toxins was described for these entries.</p>\n\n<p style="text-align: justify;"><strong>Allergenicity</strong></p>\n\n<p style="text-align: justify;">Current scientific knowledge indicates that many food allergens tend to be abundant proteins within the food product, are resistant to proteolytic digestion and heat inactivation and are often glycosylated.&nbsp; The mCry3A and PMI proteins were assessed for allergenicity by examining their digestibility, glycosylation profile, heat stability and amino acid sequence homology to known allergens.</p>\n\n<p style="text-align: justify;">The results of an <em>in vitro</em> digestive fate study using simulated gastric fluid (SGF) indicated mCry3A protein is rapidly degraded by gastric fluid. In a solution of simulated gastric fluid, 1 mg/mL mCry3A test protein mixed with simulated gastric fluid (pH 1.2, containing 2 mg/mL NaCl, 14 mL 6 N HCl, and 2.7 mg/mL pepsin) resulting in 10 pepsin activity units/ mg test protein (complies with 2000 US Pharmacopoeia recommendations), complete degradation of detectable mCry3A protein occurred within 2 minutes, determined by both SDS-PAGE and western blot analysis.</p>\n\n<p style="text-align: justify;">PMI was digested in simulated gastric fluid containing pepsin and in simulated intestinal fluid containing pancreatin.&nbsp; Samples were examined by SDS-PAGE.&nbsp; PMI was degraded rapidly by pepsin: no PMI was detected by SDS-PAGE upon immediate sampling of the reaction mix (0 seconds).&nbsp; When the pepsin was diluted to 0.0001X of the standard concentration, no PMI remained after 10 minutes of incubation.&nbsp; Similarly, no PMI enzymatic activity was detectable after 10 minutes under these conditions.&nbsp; PMI was degraded by pancreatin in simulated intestinal fluid after two minutes.&nbsp; In the unlikely event that PMI survived digestion by pepsin, it would be digested in the mammalian intestinal environment by pancreatin.&nbsp; This indicates that PMI is not stable to digestion and is unlikely to be a food allergen</p>\n\n<p style="text-align: justify;">mCry3A was assessed for glycosylation by DIG Glycan analysis.&nbsp; The limit of detection was 2.5 ng. mCry3A samples of 1000 ng were tested and neither the E. coli-expressed mCry3A nor the corn-expressed mCry3A were found to be glycosylated.&nbsp; The PMI amino acid sequence contains no consensus sequences for N-glycosylation, although O-glycosylation could theoretically occur.&nbsp; Mass spectrometric analysis of human PMI indicates that this protein is not post-translationally modified</p>\n\n<p style="text-align: justify;">The effect of temperature on mCry3A was determined by incubation for 30 minutes at a range of temperatures (4&ordm;C, 25&ordm;C, 37&ordm;C, 65&ordm;C, and 95&ordm;C) followed by a bioassay against Western corn rootworm larvae.&nbsp; At 95&ordm;C mcry3A was completely inactivated.&nbsp; Some reduction in activity was observed after incubation at 65&ordm;C and temperatures of 4&ordm;C, 25&ordm;C and 37&ordm;C had no effect on mCry3A bioactivity.</p>\n\n<p style="text-align: justify;">The heat stability of PMI was evaluated in a similar manner.&nbsp; Loss of enzyme activity was used to determine the instability of the protein after exposure to various temperatures (25, 37, 55, 65 and 95&ordm;C) for 30 minutes.&nbsp; Incubation at ambient temperature (25&ordm;C), 37&ordm;C or 55&ordm;C for 30 minutes had little effect on enzyme activity.&nbsp; Incubation at 65&ordm;C and 95&ordm;C essentially inactivated the protein.</p>\n\n<p style="text-align: justify;">To determine whether mCry3A has any significant homology with allergenic proteins, the protein sequence was systematically compared to a database of allergen sequences.&nbsp; This database was compiled from entries identified as allergens or putative allergens in public protein databases, and was supplemented with additional amino acid sequences identified from the scientific literature.&nbsp; Overall similarity was examined by comparing sequential 80-amino acid sequences covering the entire mcry3A protein sequence (such that each 80-amino acid window was offset from the previous one by one residue and overlapped by 79 residues) to the allergen sequences using the FASTA search algorithm. Any 80-amino acid peptide having greater than 35% amino acid identity was defined as having significant similarity to the allergen sequence.&nbsp; The mCry3A sequence was also screened for matches of eight or more contiguous amino acids.&nbsp; The purpose of this is to identify any short local regions of identity that might indicate the presence of common IgE binding epitopes.</p>\n\n<p style="text-align: justify;">No significant sequence homology was found between any of the sequential mCry3A 80-amino acid peptides and any entries in the database.&nbsp; No alignments of eight or more contiguous identical amino acids between mcry3A and any of the proteins in the database were identified.</p>\n\n<p style="text-align: justify;">The PMI protein sequence was compared to allergenic proteins in a similar manner and there was no significant similarity between any of the sequential PMI 80-amino acid peptides and any entries in the database.&nbsp; There was one region of eight identical amino acids between PMI and the known allergen &Alpha;-parvalbumin from <em>Rana species</em> CH2001.&nbsp; One case of severe food-induced anaphylaxis in a single individual who consumed Indonesian frogs legs has been shown to be due to the protein &Alpha;-parvalbumin from <em>Rana species</em>.&nbsp; To determine if the IgE antibodies in this patient&rsquo;s serum recognized PMI, a PMI protein sample was tested for cross-reactivity. &nbsp;</p>\n\n<p style="text-align: justify;">The PMI sample was bacterially derived and did not contain the two amino acid changes present in MIR604 PMI, however, the region of identity between PMI and &Alpha;-parvalbumin was not affected by this change and therefore the use of bacterially derived PMI would not affect the outcome of this test.&nbsp; No cross reactivity between the human serum IgE and PMI occurred.&nbsp; This indicates that the allergic patient&rsquo;s serum IgE does not recognise any portion of the PMI protein as an allergenic epitope.&nbsp; Therefore, the similarity between PMI and <em>Rana species </em>&Alpha;-parvalbumin is not considered to be biologically relevant.</p>\n\n<p style="text-align: justify;">In summary, no significant homology was found between the novel proteins and known protein allergens.&nbsp; <em>In vitro</em> digestibility studies indicate that the novel proteins are quickly digested.&nbsp; Glycosylation and thermolability studies did not indicate a cause for concern.&nbsp; It is unlikely that either mCry3A or PMI have any allergenic potential.</p>\n\n<p style="text-align: justify;"><strong>Nutritional and Compositional Data</strong><br />\nGrain and forage from transgenic event MIR604 derived plants and their near-isogenic, non-transgenic control were grown at 13 different locations over a two year period, with three replicate plots of each genotype planted in randomized complete blocks. Compositional data were statistically analyzed using a randomized block design with locations serving as the blocks. Statistical significance was assigned at p&amp;lt;0.05 indicating that the difference between the treatments was statistically different at the 5% customary level. The treatment-location interaction was also assessed.&nbsp; Values for each analyte from published literature&nbsp; were provided to assess whether statistically significant differences in the composition of the test and control maize are biologically meaningful.</p>\n\n<p style="text-align: justify;">Forage samples were analyzed for proximates and the minerals calcium and phosphorus.&nbsp; Of all the analytes measured, only the moisture level was different in MIR604 when compared with its near-isogenic non-transgenic control. However, moisture is a function of maturity and conditions at harvest and this difference was not considered meaningful. All other values measured for the analytes fell within published literature ranges.</p>\n\n<p style="text-align: justify;">The levels of various nutritional components were determined from mature grain, including: proximates (crude protein, crude fat, moisture, ash, and carbohydrate, acid detergent fibre, neutral detergent fibre, total dietary fibre); minerals (calcium, phosphorus, magnesium, copper, iron, manganese, potassium, sodium, selelnium, chromium and zinc); amino acids; fatty acids; vitamins (beta carotene, cryptoxanthin, folic acid, B1, B2, B3, B5, B6, C and tocopherols); anti-nutrients (phytic acid, trypsin inhibitor); and secondary metabolites (raffinose, furfural, ferulic acid, p-coumaric acid and inositol). &nbsp;</p>\n\n<p style="text-align: justify;">The MIR604 hybrids had statistically significantly higher levels of protein and total fat, and statistically significantly lower levels of starch and total dietary fibre than the near-isogenic non-transgenic control corn. MIR604 hybrids also had statistically significantly higher levels of the amino acids asparagine, threonine, serine, glutamate, alanine, valine, methionine, isoleucine, leucine, tyrosine, and phenylalanine than did the near-isogenic non-transgenic control corn, whereas, the control corn showed statistically higher cystine levels than did the MIR604 corn. However, mean values for all proximates and amino acids, measured for grain from MIR604 and non-isogenic non-transgenic controls were within published literature ranges and it was concluded that the differences in composition between MIR604 and control lines are not biologically significant.</p>\n\n<p style="text-align: justify;">Statistically significantly higher levels of palmitic, oleic, and linoleic acids and statistically significantly lower levels of linolenic acid in MIR604 compared to the near-isogenic non-transgenic control were noted. MIR604 also had statistically significantly higher levels of calcium and phosphorus than did their near-isogenic non-transgenic control corn. Once again, mean values for these were within published ranges and the differences in composition between MIR604 and control lines are not considered to be biologically significant.</p>\n\n<p style="text-align: justify;">Vitamin levels in both MIR604 hybrids and the near-isogenic non-transgenic controls were found to be within published literature ranges.&nbsp; The values for phytic acid were at or below literature values for both MIR604 and the near-isogenic non-trangenic control corn. The values for the other anti-nutrient, trypsin-inhibitor, and all of the secondary metabolites for both the MIR604 hybrids and the near-isogenic non-trangenic control corn were within published literature ranges.</p>\n\n<p style="text-align: justify;">The results of these compositional analyses led to the conclusion that MIR604 forage and grain is not different in nutritional and anti-nutritional composition compared to maize hybrids currently marketed, grown and consumed.&nbsp;</p>\n', 'Enabled', NULL, '2013-08-30 12:59:39'),
(78, 126, '<p style="text-align: justify;"><b>Dietary exposure:</b></p>\n\n<p style="text-align: justify;">The modification to the AHAS enzyme in BW7 will not result in any change in the consumption or use pattern of wheat and wheat-based products. The availability of many wheat cultivars for cultivation, the diversity of wheat in phenotypic traits, and the normal variation in wheat composition due to differences in growing conditions all result in a wide variation in the composition of conventional wheat grain. Since the modification to the AHAS enzyme would not be expected to change the gluten content in BW7, the cultivation and use of this wheat would not result in any new or additional concern for individuals with celiac disease. Thus, the cultivation of BW7 would not be expected to change the dietary exposure in Canada and the United States, any more than commercially available wheat cultivars.</p>\n\n<p style="text-align: justify;">Nutritional composition data was obtained from wheat event BW7 and a parental control. Grain samples were collected from replicated plots in 8 field sites in 2002, 2003 and 2005. Note that the data from 2002 and 2003 was combined. These samples were analyzed for proximates, ADF, NDF, TDF, amino acids, fatty acids, minerals and vitamins. There were no statistically significant differences between BW7 and the parental control for crude fat, protein, crude fibre, ADF, NDF, TDF in the 2002/2003 and 2005 grain samples. No statistically significant differences were observed between BW7 and the parental control for the branched- chain amino acids (valine, isoleucine and leucine). Lysine, methionine, cystine and threonine levels were not statistically significantly different between BW7 and the parental control. Stearic, oleic and linoleic acids in BW7 were statistically significantly lower than the parental control in the 2002/2003 samples, while palmitic and oleic acids in BW7 were significantly higher than the parental control in 2005. However, all fatty acids levels were shown to be comparable to those of conventional bread wheat varieties. No statistically significant differences were observed between BW7 and the parental control for all minerals in 2002/2003 samples. There were significant differences between BW7 and the parental control for phosphorous and zinc in the 2005 data, however these levels were shown to be comparable to those of conventional bread wheat varieties. All other minerals were similar for BW7 and the parental control. In 2002/2003 vitamin B6 was significantly lower in BW7 than the parental control, but the range was within the range of commercial varieties. No statistically significant differences were observed between BW7 and the parental control for all vitamins analyzed in 2005 samples.</p>\n\n<p style="text-align: justify;">Phytic acid and trypsin inhibitor were analyzed in wheat event BW7 and compared to the parental control. There were no statistically significant differences in phytic acid between BW7 and the parental control for both 2002/2003 and 2005 grain samples. The levels of trypsin inhibitor were below the limit of detection of the assay for both BW7 and the parental control.</p>\n\n<p style="text-align: justify;">The evidence provided supports the conclusion that the nutritional composition of wheat event BW7 is equivalent to conventional bread wheat varieties.</p>\n\n<p style="text-align: justify;"><b>Toxicity and Allergenicity: </b></p>\n\n<p style="text-align: justify;">The potential for toxicity and allergenicity of BW7 wheat was determined by examining the characteristics of the modified AHAS protein and the amino acid sequence homology between the modified protein and known toxins and allergens. The unmodified form of AHAS is heat sensitive and susceptible to trypsin degradation. Data from studies on the heat sensitivity and trypsin degradability of the modified AHAS in BW7 showed similar sensitivity to heat and trypsin degradability with no detectable AHAS activity after one minute at 100&deg;C. The unmodified and modified forms of AHAS show no amino acid similarity to known toxins and allergens. The modified AHAS is substantially equivalent to the unmodified enzyme in that it differs by only one amino acid. Evidence was also provided to show that the protein components of BW7 were not altered compared to those of unmodified parental controls. Results from HPLC on protein extracts demonstrated that no new major proteins or increased protein expression occurred as a result of the mutation to the AHAS enzyme. From these results it was concluded that BW7 wheat did not demonstrate any potential for toxicity and allergenicity compared to conventional unmodified wheat.</p>\n', 'Enabled', NULL, '2013-08-30 00:46:45'),
(79, 132, '<p style="text-align: justify;"><b>Dietary Exposure</b></p>\n\n<p style="text-align: justify;">Humans consume relatively little whole kernel or processed maize, compared to maize-based food ingredients. Maize is a raw material for the manufacture of starch, the majority of which is converted to a variety of sweetener and fermentation products, including high fructose syrup and ethanol. Maize oil is commercially processed from the germ. These materials are components of many foods including bakery and dairy goods, and the human food uses of grain from MON89034 are not expected to be different from the uses of non-transgenic field maize varieties. As such, the dietary exposure to humans of grain from insect resistant hybrids will not be different from that for other commercially available field maize varieties. Maize grain and by-products of wet and dry milling are used as animal feed. The whole maize plant can also be harvested at an appropriate stage and fed to animals or stored as silage. As for food use, the dietary exposure of animals to grain or forage from MON89034 will not be different to exposure from other commercially available maize.</p>\n\n<p style="text-align: justify;"><b>Potential toxicity and allergenicity</b></p>\n\n<p style="text-align: justify;">Cry1A.105 is a chimeric Cry1A protein of <i>Bacillus thuringiensis</i> that is comprised of three N-terminal domains (I, II, and III) and the C-terminal region. The domains I and II of Cry1A.105 are 100% identical to the respective domains of Cry1Ab or Cry1Ac. The domain III of Cry1A.105 is 99% identical to the domain III of Cry1F. The C-terminal region of Cry1A.105 is 100% identical to that of Cry1Ac. The overall amino acid sequence identity of 93.6%, 90.0%, and 76.7% to Cry1Ac, Cry1Ab, and Cry1F proteins, respectively. Cry2Ab2 is a <i>Bacillus thuringiensis</i> (subsp. <i>kurstaki</i>) protein. <i>Bacillus thuringiensis</i> strains producing Cry1Ac, Cry1Ab, Cry1F, and Cry2A proteins have been used for decades as biopesticides, and pesticides that contain Cry1Ac/Cry1F chimeric protein have been used since 1997. Transgenic maize and cotton expressing Cry1Ac, Cry1Ab, Cry1F, or Cry2Ab2 proteins have been cultivated in large areas in the U.S. and other countries for up to a decade. There are no known reports of allergy or toxicity to Bt or to these Cry proteins.</p>\n\n<p style="text-align: justify;">A dietary safety assessment was performed to evaluate the risks to humans and animals from the Cry1A.105 and Cry2Ab2 proteins present in the foods and feeds derived from MON89034. Risks are quantified as a margin of exposure (MOE), which is defined as the ratio of the No Observable Effect Level (NOEL) from an acute mouse gavage study to estimates of the dietary intake of the respective Cry protein. Mice acute oral toxicity studies demonstrated that the two proteins are not acutely toxic and do not cause any adverse effects even at the higest dose levels tested, which are 2072 and 2198 mg/kg body weight for Cry1A.105 and Cry2Ab2 proteins, respectively. The dietary safety assessment showed that the MOEs for the overall U.S. population were greater than or equal to 199,000 and 981,000 for the Cry1A.105 and Cry2Ab2 proteins, respectively. For children aged 3-5 years old, an age group with the highest corn consumption, the MOEs were greater than or equal to 79,400 and 390,000 for the Cry1A.105 and Cry2Ab2 proteins, respectively. For poultry and livestock, the MOEs ranged between 1,930 &ndash; 13,500 and 2,160 &ndash; 47,600 for the Cry1A.105 and Cry2Ab2 proteins, respectively.</p>\n\n<p style="text-align: justify;">Cry1A.105 and Cry2Ab2 proteins do not share any amino acid sequence similarities with known allergens, gliadins, glutenins, or protein toxins which have adverse effects to mammals. This has been shown by extensive assessments with bioinformatic tools, such as FASTA sequence alignment tool and an eight amino acid sliding window search. Furthermore, Cry1A.105 and Cry2Ab2 proteins are rapidly digestible in simulated gastric fluids. Greater than 95% to 99% of the proteins were digested in simulated gastric fluids in less than 30 seconds. Proteins that are rapidly digestible in mammalian gastrointestinal systems are unlikely to be allergens when consumed.</p>\n\n<p style="text-align: justify;"><b>Nutritional and Compositional Data</b></p>\n\n<p style="text-align: justify;">The composition of forage and grain from MON89034 and a non-transgenic control was compared to assess whether the transgenic corn differs from non-transgenic corn in nutritional characteristics. The non-transgenic control has a genetic background similar to that of MON89034 but does not contain the cry1A.105 and cry2Ab2 genes. In addition, grain and forage from 15 different conventional maize hybrids produced in the same field trials with MON89034 and the non-transgenic control was evaluated, with three different hybrids planted at each of the five sites. Data derived from these 15 conventional hybrids as references to generate a 99% tolerance interval for each analyzed component.<br />\nThe levels of proximates (ash, fat, protein and moisture), fiber (acid detergent fiber-ADF and neutral detergent fiber-NDF) and minerals (calcium and phosphorous) were compared in forage from MON89034 and the non-transgenic control. No statistically significant differences were found in the levels of all analyzed components between forage from MON89034 and forage from the conventional control, with the exception of phosphorus. MON89034 had statistically significantly higher levels of phosphorus than its control, but these levels were within the 99% tolerance intervals for the commercial varieties and within the ranges reported in the literature and the ILSI Crop Composition Database.</p>\n\n<p style="text-align: justify;">The levels of proximates, minerals, amino acids, fatty acids, anti-nutrients, secondary metabolites and vitamins were compared in mature grain from MON89034 and control maize. A statistical analysis of the analytical results combined from all field trials found no statistically significant differences between MON89034 and the conventional non-transgenic control, except for stearic acid and arachidic acid (calculated as a percentage of total fatty acids). However, differences in the levels of these fatty acids were small. The levels of all measured components were within the ranges reported in the literature and the ILSI Crop Composition Database and within the 99% tolerance interval established from the 15 control varieties. There were several statistically significant differences in the level of nutrients within the individual locations, but these differences were not consistent across all locations and it was concluded that these differences were not biologically significant.</p>\n\n<p style="text-align: justify;">The results of these compositional analyses led to the conclusion that MON89034 forage and grain are not different in nutritional and anti-nutritional composition compared to maize hybrids currently marketed, grown and consumed.</p>\n', 'Enabled', NULL, '2013-08-30 00:56:05'),
(80, 136, '<p style="text-align: justify;"><b>Food and Feed Use</b></p>\n\n<p style="text-align: justify;">Maize grain and its processed fractions are consumed as human food and animal feed. The majority of maize is used as animal feed, and a small percentage is harvested as forage and made into silage and fed to ruminants. The remainder of maize is exported, processed into food products, or converted to ethanol. Maize can be processed by wet and dry milling processes to convert the grain into food, feed, and fuel products.</p>\n\n<p style="text-align: justify;"><b>Compositional Analysis</b></p>\n\n<p style="text-align: justify;">The composition of forage and grain from event 98140 maize and a near isogenic, nontransgenic control maize was analyzed to assess whether there had been any unintentional compositional changes as a result of the genetic modification. Forage samples were analyzed for proximates (protein, fat, and ash), amino acids, free amino acids, acetylated amino acids [N-acetylaspartate (NAA) and N-acetylglutamate (NAG)], acid detergent fiber (ADF), neutral detergent fiber (NDF), calcium and phosphorus. Grain samples were analyzed for proximates, ADF, NDF, fatty acids, total amino acids, acetylated amino acids [NAA and NAG, N-acetylthreonine (NAThr), N-acetylserine (NASer), N-acetylglycine (NAGly)], free amino acids, minerals, vitamins, antinutrients, and secondary plant metabolites.</p>\n\n<p style="text-align: justify;"><b>Forage Analysis:</b> No statistically significant differences between event 98140 and the nontransgenic control samples were observed in the mean levels of proximates, minerals, carbohydrates, ADF, NDF, total and free amino acids. The mean levels were also within the 99% tolerance intervals and combined literature ranges. Literature values and statistical tolerance intervals were not available for the amino acid content of maize forage, however, most of the means for the specific amino acids fell within or close to the literature ranges for maize silage published by OECD (2002). As expected, the mean levels for NAA and NAG were statistically significantly higher (p &lt; 0.05) for the 98140 samples compared to the non-transgenic control samples. No literature data were found regarding the level of the two acetylated amino acids in maize forage. In order to address the biological significance of the elevated levels of the two acetylated amino acids, their effect on the free amino acid pool was investigated. The free amino acids in maize forage were measured in both samples of nontransgenic control maize and samples of event 98140 maize, and no significant differences were detected in the mean levels of any of the free amino acids. NAG and NAA make up less than 1.2 % of the total amino acids in event 98140 forage samples and the protein levels and free amino acid pool were comparable to the non-transgenic control samples. The low levels of acetylation of aspartate and glutamate in the forage of event 98140 did not affect amino acid incorporation into proteins or the level of the free amino acid pool.</p>\n\n<p style="text-align: justify;"><b>Grain Analysis:</b> No statistically significant differences between event 98140 and the non- transgenic control maize grain samples were observed in the mean levels of protein, ash, NDF, ADF, minerals, vitamins, antinutrients (raffinose, phytic acid, and trypsin inhibitor), secondary plant metabolites (furfural, p-coumaric acid, and ferulic acid), and fatty acids. All mean levels were within the 99% tolerance intervals and the combined literature ranges. No statistically significant differences between the 98140 and the non-transgenic control samples were observed in the mean levels of total amino acids in the grain, with the exception of the mean level of tryptophan, which was slightly higher in 98140 samples compared to control samples but still within the 99% tolerance interval and/or literature range.</p>\n\n<p style="text-align: justify;">To clarify whether low levels of acetylation of amino acids affected the composition of the free amino acid pool in event 98140 grain, levels of individual free amino acids were measured. Two non-amino acid compounds (ethanolamine and ammonia) were measured along with the amino acids because they are recognized as analytes by the method used. There were no statistically significant differences in the mean levels of the free amino acids between 98140 and the non-transgenic control samples. Furthermore, all mean levels were within the 99% tolerance intervals; hence the free amino acid pools in event 98140 grain and non-transgenic control grain samples were comparable.</p>\n\n<p style="text-align: justify;">Levels of acetylated amino acids were also compared between event 98140 and non-transgenic control grain samples. The mean levels of NAA and NAG in 98140 grain samples were 0.0403 % dw and 0.0079 % dw, respectively, compared to 0.00009 % dw and 0.00005 % dw, respectively, for control samples. It was calculated that NAA and NAG make up less than 0.05 % dw of maize grain and less than 0.5% of the total amino acids in event 98140 grain. Although the levels of NAThr, NASer, and NAGly were statistically significantly higher in 98140 grain samples than in the non-transgenic control samples, they were more than 100 fold lower than the levels of NAA and NAG. For example, the mean levels of NAThr, NASer, and NAGly in 98140 grain samples were less than 0.0003% on a dw basis.</p>\n\n<p style="text-align: justify;">In addition to being found in conventional corn grain and forage, NAA and NAG are components of commonly consumed food such as eggs, chicken, turkey, and beef. An exposure assessment for humans to compare the estimates of dietary intake of NAA and NAG with and without exposure from event 98140 maize was conducted and it was concluded that commercialization of event 98140 maize may increase the dietary exposure to NAA and NAG in the U.S. population above current levels of exposure. However, based on the relatively low level of dietary exposure as well as the presence of deacetylases (aminoacylases that deacetylate N-acetylated amino acids) in the human body, it was concluded that no safety issues are expected as a result of the estimated increased consumption of acetylated amino acids in the human diet due to commercialization of 98140 maize.</p>\n\n<p style="text-align: justify;">The biological effects of increased levels of NAA and NAG were also assessed in a 42-day broiler chicken feeding trial. No statistically significant differences were noted in mortality, weight gain, feed efficiency, and organ and carcass yield variables between broilers consuming diets produced with 98140 maize and those consuming diets produced with the non-transgenic control maize. No safety issues are expected as a result of the estimated increase in exposure to NAA and NAG in the broiler diet. Dietary exposure estimates for NAA and NAG in other livestock animal species were also calculated, and these were less than for the broiler chicken feeding trial.</p>\n\n<p style="text-align: justify;"><b>Potential Allergenicity and Toxicity</b></p>\n\n<p style="text-align: justify;">The GAT4621 and ZM-HRA proteins were evaluated for potential allergenicity and toxicity using a weight of evidence approach that examined: amino acid sequence similarities with known allergens and toxins, digestibility in model pepsin (simulated gastric fluid) and pancreatin (simulated intestinal fluid) systems, post-translational modification, and characteristics of the donor organism. Neither protein displayed significant amino acid sequence similarity with known allergens or toxins, both proteins were rapidly and completely digested in SGF within 30 seconds, and neither protein is glycosylated.</p>\n\n<p style="text-align: justify;">The potential toxicity of GAT4621 protein was also assessed in an acute oral toxicity study in mice. A single dose of 1640 milligrams per kilogram of body weight (mg/kg bw) of <i>E. coli</i>-produced and purified GAT4621 protein was administered by oral gavage to five male and five female mice. No clinical symptoms of toxicity, body weight loss, gross organ lesions, or mortality were observed. It was concluded that GAT4621 protein is not acutely toxic. A similar study was conducted using the ZM-HRA protein with mice (5 male and 5 female) receiving a single oral dose of 1236 mg/kg bw of <i>E. coli</i>-produced and purified ZM-HRA protein. No clinical symptoms of toxicity, body weight loss, gross organ lesions, or mortality were observed, indicating that the ZM-HRA protein is not acutely toxic.</p>\n', 'Enabled', NULL, '2013-08-30 01:02:25'),
(81, 137, '<p style="text-align: justify;"><b>Food and Feed Use</b></p>\n\n<p style="text-align: justify;">Maize event MIR162 will be grown for the same uses as maize varieties currently commercially available in the United States. While maize grown in the United States is predominantly (roughly 60 percent) used to feed domestic animals, either as grain or silage, maize grain is also processed by wet or dry milling to yield food products such as high fructose corn syrup, starch, oil, grits, and flour. Non-food/feed purposes for grain include use for fuel ethanol production; however, the by-products of such industrial distilling processes may also be used in animal feeds. Maize event MIR162 is suitable for the same uses as conventional maize.</p>\n\n<p style="text-align: justify;"><b>Compositional Analysis</b></p>\n\n<p style="text-align: justify;">Key nutritional components in maize grain and forage derived from event MIR162 and near-isogenic non-transgenic control plants were compared. Replicate trials of transgenic and corresponding near-isogenic non-transgenic control hybrids were planted in multiple locations selected to be representative of the range of environmental conditions under which the hybrid varieties would typically be grown. Samples of grain and forage were harvested from six of these trial locations and compositional data for the MIR162 and control hybrids were subjected to analysis of variance across all locations and compared to compositional analysis data for grain and forage published in the literature and in compositional analysis databases.</p>\n\n<p style="text-align: justify;">Among the numerous compositional analyses that were carried out, most showed no consistent statistically significant differences. Statistically significant differences were noted for levels of the proximates ash, NDF and starch; the minerals calcium, iron and phosphorus; vitamins A (b-carotene), B6 and E (a-tocopherol); linoleic and linolenic fatty acids; the secondary metabolites ferulic acid and p-coumeric acid; and the phytosterol, b-sitosterol. However, the magnitudes of the differences were small and in every case the average values (when quantifiable) were all within the ranges of natural variation as reported in the literature. Overall, no consistent patterns emerged to suggest that biologically significant changes in composition or nutritive value of the grain or forage had occurred as an unintended result of the transformation process or expression of the Vip3Aa20 or PMI proteins.</p>\n\n<p style="text-align: justify;">The conclusion based on these data was that grain and forage from MIR162 maize were substantially equivalent in composition to both the non-transgenic control hybrid included in this study, and to other commercial maize hybrids.</p>\n\n<p style="text-align: justify;"><b>Potential Toxicity and Allergenicity</b></p>\n\n<p style="text-align: justify;">The potential toxicity and allergenicity of the Vip3Aa20 and PMI proteins expressed in event MIR162 maize was evaluated by acute oral toxicity testing, digestive fate, and heat stability studies. In addition, amino acid sequence homology searches were performed against known toxins and allergens. Neither the Vip3Aa20 protein nor the PMI protein produced any adverse effects in laboratory mice challenged with a single oral dose corresponding to 1250 mg/kg body weight or 3080 mg/kg body weight, respectively. Both the Vip3Aa20 and PMI proteins were rapidly degraded following exposure to pepsincontaining simulated gastric fluid, indicating that any Vip3Aa20 or PMI protein in the diet would be readily digested as conventional dietary protein. In addition, the Vip3Aa20 and PMI proteins were both shown to lose biological (Vip3Aa20) or enzymatic (PMI) activity following incubation at 65&ordm;C for 30 minutes. Neither the Vip3Aa20 protein nor the PMI protein shows significant amino acid sequence similarity to known or putative mammalian toxins or to allergenic protein sequences that are biologically relevant or have implications for allergenic potential. Based on this weight-of-evidence approach, it was concluded that the Vip3Aa20 and PMI proteins expressed in event MIR162 were extremely unlikely to exhibit mammalian toxicity or allergenicity.</p>\n', 'Enabled', NULL, '2013-08-30 01:03:59');
