<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>

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

<p style="text-align: justify;">Kernel composition, quality and other characteristics of CBH-351 maize were not significantly different from non-transgenic maize.</p>

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

<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 />
A 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>

<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>

<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>

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

<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>

<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>

<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>

<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>
