Oral subchronic and genotoxicity studies conducted with the amino acid, L-glutamine.

L-Glutamine is an abundantly occurring amino acid that serves numerous nutritional and physiological functions. It has current and potential applications as a therapeutic agent, dietary supplement, food ingredient, and in animal nutrition. To assess the safety of supplemental L-glutamine, a bacterial reverse mutation assay, in vitro chromosomal aberration assay, and a 13-week toxicity study were conducted. L-Glutamine showed no mutagenic activity in the bacterial reverse mutation assay, and did not induce chromosomal aberrations in Chinese hamster lung fibroblast cells in the in vitro chromosomal aberration assay. In the 13-week toxicity study, Sprague-Dawley rats (10/sex/group) were fed diets containing 0, 0.5, 2.5, or 5.0% L-glutamine. No deaths occurred, and no significant differences in body weights, body weight gains, ophthalmological findings, urinalysis parameters, or organ weights were observed between L-glutamine-fed rats and their respective controls. No toxicologically relevant effects on hematological or blood biochemical parameters were observed. Macroscopic and microscopic effects occurred at low frequency but were not associated with a dose-response relationship. Based on the results of the study, the no-observed-adverse-effect-level was determined to be 5.0% L-glutamine in the diet, the highest concentration tested (equivalent to 3832 and 4515 mg/kg body weight/day in male and female rats, respectively).