US EPA

196255 

Journal Article 

Toxicity of aspartame and its diketopiperazine for Wistar rats by dietary administration for 104 weeks 

Ishii, H; Koshimizu, T; Usami, S; Fujimoto, T 

1981 

1 

Toxicology
ISSN: 0300-483X
EISSN: 1879-3185 

21 

2 

91-94 

7281205 

10.1016/0300-483X(81)90119-0 

http://www.sciencedirect.com/science/article/pii/0300483X81901190
Exit
 

Aspartame (APM) or L-aspartyl-L-phenylalanine, and a 3 : 1 combination of APM with its decomposition product, 5-benzyl-3,6-dioxo-2-piperazine acetic acid (DKP), were incorporated at levels of up to 4 g/kg in the diet of male and female Wistar rats from 6 weeks to 104 weeks of age. There was a dose-dependent depression of body weight gain at 2 and 4 g/kg AMP and at 4 g/kg APM + DKP in males, and at all dose levels in females, correlated with decreased food consumption and attributed to liberation of amino acids from hydrolysis of APM. Increases in urinary specific gravity and pH, with increase of relative kidney weight, were attributed to the urinary excretion DKP and acidic metabolites of APM. A dose-related increase in urinary calcium probably reflected increased calcium absorption, as from high protein diets. A slight decrease in serum cholesterol and an increase in relative spleen weight appeared to be without adverse effect. It is concluded that the treatments were without toxic effect.