<p style="text-align: justify;"><b>Dietary Exposure</b></p>

<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>

<p style="text-align: justify;"><b>Toxicity and Allergenicity</b></p>

<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>

<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>

<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>

<p style="text-align: justify;"><b>Nutritional Data</b></p>

<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>

<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>
