ABSTRACT
Since aspartame forms a diketopiperazine under certain conditions of storage or food processing, toxicological studies were conducted on aspartame’s diketopiperazine. Animals were evaluated with respect to physical appearance, behavior, body weight, food and water consumption, survival, clinical laboratory data, and at postmortem for organ weight as well as for gross and microscopic pathology. Histopathological examination of the kidneys of rats killed at 104 weeks showed a dose-related increase in the number of animals with focal mineralization. The foci were found as minute mineral deposits in a few epithelial cells, unrelated to epithelial hyperplasia or inflammatory response. Criteria used to evaluate safety included physical appearance, behavior, growth, food consumption, survival, clinical laboratory data, ophthalmologic examinations, organ weights, tumor incidence, and gross and microscopic pathology. Deposits of hemosiderin in renal tubular or pelvic epithelial cells of male survivors and nonsurvivors were increased at the higher treatment levels.
