Safety evaluation of certain food additives - ipcs inchem

48 ETHYL LAUROYL ARGINATE
only) 240 min after treatment with [ 14 C]ethyl lauroyl arginate. Human plasma
samples and cryopreserved hepatocytes were incubated with [ 14 C]ethyl lauroyl
arginate for up to 4 h and 3 h, respectively. All samples were analysed by HPLC to
determine the proportions of ethyl lauroyl arginate and any degradation products.
Ethyl lauroyl arginate was stable in simulated gastric fluid with or without
pepsin, over a period of 2 h, representing at least 96.1% of the sample radioactivity.
In simulated intestinal fluids containing pancreatin (at both pH 6.8 and 7.5), ethyl
lauroyl arginate was immediately degraded to N -lauroyl-L-arginine, which was
subsequently degraded to arginine. At zero time, N -lauroyl-L-arginine and arginine
represented 95.2–98.2% and 1.8–4.8% of the sample of radioactivity, respectively.
After 240 min, these proportions were reversed, and ethyl lauroyl arginate was not
detected in any of these samples. In the absence of pancreatin, ethyl lauroyl
arginate was stable at all time points at pH 7.5 and up to 30 min at pH 6.8, after
which it started to degrade to N -lauroyl-L-arginine. In human plasma and
hepatocytes, ethyl lauroyl arginate degraded to N -lauroyl-L-arginine over the
course of the incubation period. Radioactivity levels decreased from 98.4% at zero
time to 51.3% at 4 h (plasma) and from 75.7% at zero time to 6.1% at 3 h
(hepatocytes). Arginine was not detected in these samples (Huntingdon Life
Sciences Ltd, 2003a).
2.1.3 Effects on enzymes and other biochemical parameters
No information was available.
2.2 Toxicological studies
2.2.1 Acute toxicity
Acute toxicity studies of ethyl lauroyl arginate and associated formulations
are summarized in Table 4.
2.2.2 Short-term studies of toxicity
(a) Ethyl lauroyl arginate
Groups of five male and five female Han Wistar rats were given diets
containing ethyl lauroyl arginate (purity, 89.4% ethyl-N -lauroyl-L-arginate HCl) at
concentrations of 0, 25 000, 37 500 or 50 000 mg/kg diet (equal to 0, 2353, 3438
and 4273 mg/kg bw per day for males; and 0, 2379, 3329 and 4641 mg/kg bw per
day for females) for 4 weeks continuously. This was a preliminary toxicity study,
conducted in accordance with GLP and OECD guidelines, to determine acceptable
dosages for a 13-week dietary study. Animals were inspected at least twice daily
throughout the study. Body weights were recorded prior to dosing, at the end of
week 1, twice weekly for weeks 2–4 and before a detailed necropsy. Mean weekly
food consumption for each animal was calculated, as well as mean food conversion
efficiencies for each treatment group. Just prior to necropsy, blood samples were
taken from the retro-orbital sinus, and an extensive range of haematological and
blood chemistry tests were performed. A wide range of organs and tissues were