Safety evaluation of certain food additives - ipcs inchem

ETHYL LAUROYL ARGINATE 55
fibrosis and inflammation of the non-glandular epithelium and reflected the
depressions noted in the forestomach at necropsy. The observations were
significantly different from control only in the group treated with 18 000 mg/kg diet.
The authors considered that these changes represented a local response to
irritation and thus were not indicative of direct systemic toxicity. No other changes
were observed in the non-glandular region of the forestomach, and there were no
changes in the glandular region. There were no treatment-related effects on organ
weights. The authors concluded that no significant toxicological effects were
observed in the animals receiving 2000 or 6000 mg/kg diet and that the NOAEL was
6000 mg ethyl lauroyl arginate/kg diet (equal to 307 mg ethyl lauroyl arginate/kg bw
per day). The lowest-observed-adverse-effect level (LOAEL) was concluded to be
18 000 mg ethyl lauroyl arginate/kg diet (equal to 907 mg ethyl lauroyl arginate/kg
bw per day), based on local irritant changes in the forestomach and low body weight
gain (Huntingdon Life Sciences Ltd, 2005a).
The Committee concluded that the changes seen in the stomach
represented local irritation in the forestomach caused by storage of ingested diet
and were thus not indicative of systemic toxicity. The Committee noted that the
observed effects on leukocytes were inconsistent within and between studies and
were not likely to be biologically significant. Furthermore, the changes were not
accompanied by histopathological changes in the progenitor cell populations of the
bone marrow or lymphoid tissue, which would be expected if the effect were due to
systemic toxicity. Therefore, the Committee concluded that the highest dietary
concentration tested, 18 000 mg/kg (equal to average doses of ethyl lauroyl arginate
of approximately 900 mg/kg bw per day in male rats and 1100 mg/kg bw per day in
female rats), was the NOAEL for systemic toxicity.
2.2.4 Genotoxicity
Several studies, carried out in compliance with GLP and OECD guidelines,
were performed to investigate the mutagenicity of ethyl lauroyl arginate, a
formulation containing ethyl lauroyl arginate in propylene glycol/water and N -
lauroyl-L-arginine (Table 5). Ethyl lauroyl arginate, the formulation and N -lauroyl-
L-arginine were tested in a reverse mutation assay (Ames test). Ethyl lauroyl
arginate and the formulation were also tested for mutagenic potential in a
mammalian cell mutation assay (mouse lymphoma L5178Y cells) and for the ability
to induce chromosomal aberrations in human lymphocytes. N -Lauroyl-L-arginine
was assessed in an in vivo test for induction of micronuclei in mouse bone marrow
cells. Ethyl lauroyl arginate, the formulation and N -lauroyl-L-arginine showed no
evidence of mutagenic or clastogenic activity in any of these assays.
2.2.5 Reproductive toxicity
In a preliminary study conducted to GLP and OECD guidelines, the effects
of ethyl lauroyl arginate (purity, 88.2% ethyl-N -lauroyl-L-arginate HCl) on
reproductive performance were assessed. Ethyl lauroyl arginate was administered
to Crl:CD rats at dietary concentrations of 0, 1500, 5000 or 15 000 mg/kg (equal to
0, 113, 380 and 1151 mg/kg bw per day for males; and 0, 123, 432 and 1295 mg/
kg bw per day for females). These dietary concentrations were selected based on