Genotoxicity and subchronic oral toxicity of L-ornithine monohydrochloride.

L-Ornithine monohydrochloride was evaluated in two in vitro genotoxicity assays and a rat 90-day oral toxicity study. No evidence of genotoxicity was observed in the reverse bacterial mutation assay or the chromosome aberration test at doses of up to 5000 μg/plate or 1686 μg/mL, respectively, both in the presence and absence of metabolic activation. Rats were administered L-ornithine monohydrochloride at dietary concentrations of 0 (basal diet), 1.25%, 2.5%, or 5.0% for 90 days. No changes in body weight, food consumption, ophthalmoscopy, or hematology were observed. Transient increases in water intake and urinary volume, and a decrease in specific gravity were observed in males receiving 5.0% L-ornithine monohydrochloride; however, these were likely attributable to the central role of ornithine in the urea cycle and the consequent increase in urea production. A decrease in serum chloride concentration and an increase in urinary chloride excretion were observed; however, these were likely attributable to administration of the hydrochloride salt of ornithine and were not considered to be of any toxicological significance. No remarkable findings were noted at necropsy. Based on the results of the study, a no-observed-adverse effect level (NOAEL) of 3445 and 3986 mg/kg body weight/day was established for male and female rats.