N-acetyl-glutamic acid: Evaluation of acute and 28-day repeated dose oral toxicity and genotoxicity

• Published in: Food and chemical toxicology 2009-11, Vol.47 (11), p.2723-2729
• Main Authors: Harper, Marc S., Amanda Shen, Z., Barnett, John F., Krsmanovic, Ljubica, Myhre, Abby, Delaney, Bryan
• Format: Article
• Language: English
• Subjects: 28-day study; Acute toxicity; Administration, Oral; animal models; Animals; Bacterial mutagenicity; Biological and medical sciences; Blood Coagulation - drug effects; Bone marrow micronucleus assay; Chemical mutagenesis; dosage; dose response; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; genotoxicity; Glutamates - administration & dosage; Glutamates - toxicity; glutamic acid; Male; Medical sciences; Mice; Mice, Inbred ICR; Mutagenicity Tests; N-acetyl-glutamic acid; oral administration; Rats; Rats, Sprague-Dawley; toxicity; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2009.07.036

N-acetyl-glutamic acid (NAG) is an endogenously produced mammalian substance and minor constituent of commonly consumed foods. This paper reports the outcome of genotoxicity and acute and repeated dose (28-day) oral toxicology studies conducted with NAG. No evidence of genotoxicity was observed with NAG in in vitro or in vivo studies. No mortalities or evidence of adverse effects was observed in Sprague–Dawley rats following acute oral gavage with NAG at a dose of 2000 mg/kg of body weight. No adverse effects were observed in rats following repeated dose dietary exposure to NAG at target concentrations corresponding to doses of 100, 500, or 1000 mg/kg of body weight/day for 28 days. All rats survived until scheduled sacrifice and no biologically significant or test substance related differences were observed in body weights, feed consumption, clinical signs, functional observational battery (FOB), ophthalmology, hematology, coagulation, clinical chemistry, organ weights or histopathology of any of the treatment groups. Based on the observed results it is concluded that NAG is not genotoxic or acutely toxic. The no-observed-adverse-effect-level (NOAEL) for systemic toxicity from repeated dose (28-day) dietary exposure to NAG was 914 mg/kg of body weight/day for male rats and 1007 mg/kg of body weight/day for female rats.