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.

Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol.

Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen. We evaluated the genotoxic potential of glycidol linoleate (GL), a primary GE found in an edible oil (diacylglycerol oil), and G, using three established genotoxicity tests (a bacterial reverse mutation test, an in vitro chromosomal aberration test, and an in vivo bone marrow micronucleus test) under GLP conditions complying with all OECD guidelines. In the bacterial reverse mutation test, GL and G showed positive responses. The positive responses of GL were less than those of G and observed only in strains detecting point mutations where G showed remarkably positive responses. G was involved in the positive response of GL. In the chromosomal aberration test, GL did not induce chromosome aberrations whereas G induced structural chromosome aberrations in the presence and absence of metabolic activation. In the bone marrow micronucleus test, neither GL nor G induced significant increases of micronucleated immature (polychromatic) erythrocytes in bone marrow of test animals. Based on the above results as well as pertinent information on toxicokinetics, GL itself does not play a key role in genotoxic action.