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

<p style="text-align: justify;">EH92-527-1 is not intended for food use. For this reason, a far-reaching quality assurance system has been established for keeping EH92-527-1 separate from other potatoes. This system, in combination with the innate characteristics of the potato, makes it very unlikely that EH92-527-1 will get into the food chain. However, the possibility cannot be completely ruled out.</p>

<p style="text-align: justify;">Starch rich in amylopectin does not constitute a health risk to normal healthy individuals. However, the branched starch molecule (amylopectin) is digested more quickly than the non-branched starch molecule (amylose), and this could result in undesirable effects for diabetics. It is therefore important that EH92-527-1 be kept well separated from other potatoes so as to avoid confusion with food potatoes. The observed difference in starch composition (from 85% amylopectin and 15 % amylose in Prevalent to 98% amylopectin and 2% amylose in EH92-527-1) is believed to be of no importance in cases of low or temporary intake.</p>

<p style="text-align: justify;">EH92-527-1 produces only one new protein, NPTII, which has not been shown to be either toxic or allergenic.</p>

<p style="text-align: justify;">The byproduct EH92-527-1 pulp, which is the material that remains after the starch has been extracted, will be used as bovine feed. As noted below, statistically significant differences in nutrient composition exist between EH92-527-1 and its parental cultivar Prevalent&mdash;in particular, with respect to higher levels of mono- and disaccharides, higher levels of vitamin C, and lower levels of glycoalkaloids. The measured differences fall within the natural variation interval for potatoes and are deemed to be of little significance. The feed product is considered to be substantially equivalent to the corresponding non-GM product and consequently no health risk is believed to exist.</p>

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

<p style="text-align: justify;">The analyzed compounds with regard to composition included dry matter, protein, fat, ash, carbohydrates, fiber, digestive fiber, fructose, glucose, sucrose, starch, chlorogenic acid, solanine, chaconine, nitrate, vitamin C, and minerals (Na, K, Ca, Mg, P, Fe, Zn, Cu, Mn, Cd). Composition data were obtained from field trials performed in 1996-1998. In addition to the intended differences in starch composition, some statistically significant differences were observed each year between EH92-527-1 and its parental cultivar Prevalent. These differences included decreases in yield and dry matter and increases in sucrose content and vitamin C content. Additional data on potato EH92-527-1 tested during starch production trials in 1998-2000 showed similar values for yield compared with equivalent potato cultivars. Although additional differences were noted during single years, these were not consistently noted through three years. These differences included decreases in glycoalkaloid levels (solanine and chaconine) in potato EH92-527-1 during two years. The changes in vitamin C and glycoalkaloids were within the background ranges reported in the literature. The change in sucrose content was considered as being related to the intended alteration of starch biosynthesis. It should be noted that nitrates are found in the entire plant and are considered anti-nutritional. It was concluded that the observed differences are unlikely to cause adverse health effects. In addition, analyses of the gross and mineral compounds of pulp and juice derived from potato EH92-527-1 and the non-transgenic cultivar Prevalent showed that their compositions were similar. Taken together, the characteristics of the EH92-527-1 potato, its compositional characteristics due to the introduced trait, the anticipated intake and exposure and the presence and safe use of the starch component amylopectin in the food supply, the EH92-527-1 event is considered to pose negligible risk to human health.</p>

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

<p style="text-align: justify;">The main toxic or anti-nutritional substances in potatoes are glycoalkaloids and nitrates. Glycoalkaloids, which are toxic in high concentrations, are found in harmful amounts chiefly in the above-ground parts of the plant (e.g., stems, leaves, and fruits). Nitrates are found in the entire plant and are considered anti-nutrients.</p>

<p style="text-align: justify;">As noted earlier, statistically significant changes in nutrient composition exist between EH92-527-1 and its parental cultivar Prevalent&mdash;in particular, with respect to higher levels of mono- and disaccharides, higher levels of vitamin C, and lower levels of glycoalkaloids. The measured differences fall within the natural variation interval for potatoes and are deemed to be of little significance.</p>

<p style="text-align: justify;">A total of eighteen open reading frames (ORFs) have been identified in the insert sequence of the potato EH92-527-1. Eleven of these have no sequence homology with known coding regions. Bioinformatic analysis has shown that, for all ORFs identified, there are no homologies with known toxins or allergens.</p>

<p style="text-align: justify;">The only ORF having a complete coding region for a known protein is the nptII gene. Bioinformatic analysis indicates that ORF4 could be transcribed due to its association with ORF1 (nptII). However, a translation start in the correct reading frame is absent and a stop codon is present before ORF4. The hypothetical ORF4 protein showed a high degree of similarity with two proteins that are not known to be toxic or allergenic. Furthermore, extensive studies indicated that, while OR4 transcript is detectable in the GM potato, there is no corresponding translation into protein. It is therefore concluded to be unlikely that the presence of ORF4 in EH92-527-1 would constitute a risk. No toxicity of the NPTII protein has been observed and in simulated digestive fluids this protein is rapidly degraded. In addition, two animal studies have indicated no adverse effects on animal health. A subchronic 90-day feeding study in rats with freeze-dried potatoes derived from EH92-527-1 and its parental line failed to reveal any effects that would raise concern about the transgenic potato. An eight-week nutritional animal feeding study with pulp derived from EH92-527-1 and conventional pulp fed to heifers provided evidence of nutritional equivalence and revealed no detrimental effects on animal health.</p>

<p style="text-align: justify;">The gene sequences introduced to suppress GBSS expression have no homology with known toxins.</p>

<p style="text-align: justify;">The weight of evidence from these studies, taken together, indicates that EH92-527-1 and derived products are no more likely to cause adverse effects on human and animal health than conventional potatoes in the context of the proposed uses.</p>

<p style="text-align: justify;">The application and approval do not include food use, therefore no complete food evaluation has been performed. It is therefore very important that the EH92-527-1 potato be kept out of the food chain. A sophisticated quality-assurance system has been developed for keeping EH92-527-1 separate from other potatoes. It is believed that the combination of this program with the characteristics of the potato will make it extremely unlikely that EH92-527-1 will get into the food chain.</p>

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

<p style="text-align: justify;">EH92-527-1 produces only one new protein, NPTII, which has been shown not to be allergenic.</p>

<p style="text-align: justify;">The hypothetical ORF4 protein showed a high degree of similarity with two proteins that are not known to be toxic or allergenic. In addition, when screened against a database of sequences of allergenic proteins, the ORF4 protein sequence does not show any similarities that are believed to be relevant or to raise concerns about potential allergenic risk.</p>

<p style="text-align: justify;">Allergenicity of the whole crop could be increased as an unintended effect of the random insertion of the transgene in the genome of Prevalent, for example through qualitative or quantitative modifications of the pattern of expression of endogenous proteins. This issue does not appear relevant because potato is not considered a major allergenic food, and possible over-expression of any endogenous protein that is not known to be allergenic would be unlikely to alter the overall allergenicity of the whole plant. The same considerations also apply to exposure by inhalation during processing. Should the high amylopectin potato be inadvertently consumed, the data supporting its equivalence to the non-modified parent variety would indicate that it is no more of a potential allergen than the non-modified parent.</p>
