Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to an application on the use of ethyl lauroyl arginate as a food additive

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food has been asked to evaluate the safety in use of ethyl lauroyl arginate as a food preservative for use in the food categories specified in the dossier. The active ingredient of ethyl lauroyl arginate, ethyl-Na-lauroyl-L-arginate HCl, is the hydrochloride salt of an N-fatty acylsubstituted amino acid ethyl ester. Ethyl lauroyl arginate is intended to be used as a preservative. The anti-microbial activity of ethyl lauroyl arginate is due to the cationic surfactant properties of its active ingredient ethylNa-lauroyl-L-arginate. Ethyl lauroyl arginate has been shown by in vivo and in vitro studies in rats and humans to be rapidly metabolised by hydrolysis of the ethyl ester and lauroyl amide to the intermediate products, arginine ethyl ester and Na-lauroyl-L-arginine, and then to ethanol, lauric acid and arginine. Arginine undergoes natural amino acid catabolism to urea and ornithine. Ornithine can then be further metabolised to CO2 and urea. Lauric acid is a fatty acid that can enter normal fatty acid metabolism. Ethanol can be converted by alcohol dehydrogenase and aldehyde dehydrogenase to acetate, which can enter normal biochemical pathways. It is concluded that, on ingestion by humans, ethyl lauroyl arginate will be broken down to products of normal metabolism. The Panel considered the bacterial reverse mutation assay study could not be used for evaluation of mutagenicity due to the high toxicity of ethyl-Na-lauroyl-L- arginate towards the bacterial cells. The Panel noted that this toxicity was predictable since ethyl-Na-lauroyl-Larginate is a preservative with antimicrobial activity. Based on the results from the mouse lymphoma L5178Y cell mutation test and from the test for chromosomal aberrations in human lymphocytes it is concluded that ethyl-Na-lauroyl-L- arginate is not genotoxic in mammalian cells. It showed no evidence of a genotoxic effect in the in vivo mouse micronucleus test. According to the available evidence, ethyl lauroyl arginate is devoid of reproductive and developmental toxicity. Long-term carcinogenicity studies are lacking. However, the rapid metabolism of ethyl-Na-lauroyl-L-arginate to compounds endogenously present in much higher levels, the absence of preneoplastic toxic effects in the in vivo studies performed, together with the absence of genotoxic activity in the mouse lymphoma assay, the human lymphocyte assay and the micronucleus test, does not suggest a carcinogenic potential. Therefore the Panel concludes that there is no need to perform carcinogenicity studies. The Panel notes that effects on white blood cells were seen in different rat strains and in different sexes in two 90-day studies and in the 52-week study and concludes that these effects cannot be disregarded. Therefore the Panel concludes, given the fact that the effects on white blood cell counts at 26 weeks are significant for all dose groups, that the NOAEL for this 52 week study is lower than the lowest dose levels tested, and thus lower than 106 mg/kg bw/day. This is in line with the NOAEL of 47 and 56 mg ethyl lauroyl arginate /kg bw/day for males and females respectively from the 13 week study with the 19.5 % formulation of ethyl lauroyl arginate in propylene glycol. Based on this NOAEL and a safety factor of 100, the Panel established an ADI of 0.5 mg ethyl lauroyl arginate of the proposed specifications /kg bw. The safety factor of 100 is considered sufficient in spite of the fact that the ADI is based on a 90-day study because the effects on white blood cells do not become more severe upon prolonged exposure. Potential dietary exposure to ethyl lauroyl arginate was estimated based on UK food consumption data and on the assumption that it would be present in all food categories for which use levels are proposed. Potential dietary exposure was found to be at or above the ADI in high consumers for both children aged 1.5 to 4.5 (580% of the ADI), children aged 4 to 18 (370% of the ADI) and adults (100% of the ADI). Potential mean dietary exposure to ethyl lauroyl arginate in consumers only was also at or above the ADI for both children aged 1.5 to 4.5 (170% of the ADI) and children aged 4 to 18 (106% of the ADI).