Safety evaluation of certain food additives - ipcs inchem

78 ETHYL LAUROYL ARGINATE
3.5 Summary of dietary exposures
A summary of the estimates of dietary exposure to ethyl lauroyl arginate is
presented in Table 8.
Table 8. Summary of estimates of dietary exposure to ethyl lauroyl arginate
(as ethyl-N -lauroyl-L-arginate HCl)
Source Mean dietary exposure
(mg/kg bw per day)
GEMS/Food 1–5 –
Sponsor 3.0 5.6a USA – GRAS Notice 2.2 4.2
EU – DAFNE 0.32 (0.14–0.50) –
EU – United Kingdomb 0.11–0.83 0.37–2.9c Theoretical maximum (bounding
estimate)
– 6
High dietary exposure
(mg/kg bw per day)
a 90th percentile.
b Unclear if these data are expressed as ethyl lauroyl arginate or as ethyl-N -lauroyl-L-arginate
HCl.
c 97.5th percentile.
4. COMMENTS
4.1 Toxicological data
The metabolism of ethyl lauroyl arginate has been well characterized.
Studies with radiolabelled ethyl lauroyl arginate in vitro and in vivo show that it is
well absorbed and rapidly metabolized by hydrolysis of the ethyl ester and lauroyl
amide, via N -lauroyl-L-arginine and, to a lesser extent, L-arginine ethyl ester, to
arginine, lauric acid and ethanol. Arginine subsequently undergoes normal amino
acid catabolism via the urea and citric acid cycles, with ultimate elimination as
carbon dioxide in the expired air and urea in the urine. Lauric acid enters normal
fatty acid metabolism, and ethanol is converted to acetate, which enters normal
biochemical pathways. Both lauric acid and ethanol are also present naturally in
foods. After administration of [ 13 C]ethyl lauroyl arginate, the dose-corrected AUC for
N -lauroyl-L-arginine in humans was 60-fold that in rats. The plasma concentrations
of arginine were higher than those of N -lauroyl-L-arginine, indicating that most of
the ethyl lauroyl arginate is metabolized before absorption. Given the rapid
degradation of ethyl lauroyl arginate, exposure to this compound and N -lauroyl-Larginine
in vivo is likely to be short.
Ethyl lauroyl arginate is of low acute toxicity. In a 13-week feeding study in
rats, the major observations were forestomach changes, such as erosions,
ulcerations and epithelial hyperplasia, indicating an irritant action, at dietary