Assessment of the Nephrotoxic Effect of a Combined Exposure to Melamine and Cyanuric Acid

<OL> <LI> Conduct a pharmacokynetic study on F344/N rats on the absorption and disposition of melamine and cyanuric acid when administered individually by gavage, simultaneously as a separate base and acid, and simultaneously as a preformed salt (melamine cyanurate). </LI>
<LI>Determine the NOAEL of a combined exposure to melamine and cyanuric acid in F344/N rats for 28 and 90 days.</LI>

<LI> Investigate the occurrence of early metabonomic and proteomic biomarkers of melamine + cyanuric acid-induced nephrotoxicity obtainable by noninvasive methods. </LI>

<LI>Investigate the pharmacokinetics and determine the NOAEL of a combined exposure to melamine and cyanuric acid in a mini-pig model deemed to be representative of the human-kidney anatomy and physiology.</LI>
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