Toxicological and metabolic investigations of the safety of N-α-lauroyl-L-arginine ethyl ester monohydrochloride (LAE)

Studies were conducted to assess the safety of N-alpha-lauroyl-L-arginine ethyl ester monohydrochloride, (LAE), a novel food preservative, or Mirenat-N (a 25% solution of LAE in propylene glycol). Short term studies demonstrated low acute toxicity. LAE was shown to have mild dermal irritation effects but neither LAE nor Mirenat-N are skin sensitizers. LAE was demonstrated to be a severe eye irritant. In two 13-week feeding studies in rats, systemic NOAELs were established for LAE at 15,000 ppm and for Mirenat-N at 50,000 ppm. There were no signs of neurotoxicity with LAE after 13-weeks at dietary levels as high as 50,000 ppm. Embryo-fetal studies with LAE in rats and rabbits showed no developmental effects at oral gavage doses up to 2000 and 1000 mg/kg/day for rats and rabbits, respectively. NOAELs for systemic maternal effects (reduced food intake and body weights in rabbits) were 2000 mg/kg/day for rats and 300 mg/kg/day for rabbits. In a battery of 5 in vitro genotoxicity tests with LAE or Mirenat-N, neither material was observed to have genotoxic (clastogenic or mutagenic) activity. Metabolism studies with LAE show that it is rapidly metabolized to the amino acid arginine by hydrolysis of the ethyl ester and lauroyl amide functions. The arginine subsequently enters the naturally occurring urea cycle where it is further metabolized to ornithine and urea and eventually to CO2 through normal mammalian biochemical pathways. The other product of LAE cleavage is lauric acid, which is a human dietary component found in many plant sources, and as such, would enter into normal fatty acid metabolism. (C) 2003 Elsevier Ltd. All rights reserved.