Safety evaluation of certain food additives - ipcs inchem

ETHYL LAUROYL ARGINATE 79
concentrations of 15 000 mg/kg and greater. In addition, body weight gain and
leukocyte counts were significantly decreased in males but not in females. No
adverse effects were observed with ethyl lauroyl arginate at a dietary concentration
of 5000 mg/kg, equal to 384 mg/kg bw per day. In another 13-week study in rats
given diets containing a formulation of 19.5% ethyl-N -lauroyl-L-arginate HCl in
propylene glycol, body weight gain and leukocyte counts were significantly
decreased in females, but not in males, at dietary concentrations of 12 800 and
50 000 mg/kg, equal to 208 and 766 mg/kg bw per day. No treatment-related
changes were observed by histopathological examination.
Decreased food consumption and body weight gain were observed in
rats that were given ethyl lauroyl arginate at dietary concentrations of 6000 or
18 000 mg/kg for 52 weeks; these findings are likely to have been due to reduced
palatability of the diet. Ethyl lauroyl arginate caused a dose-related irritation of the
mucosal tissue of the forestomach, which was statistically significantly different from
controls, at 18 000 mg/kg, but not at 6000 or 2000 mg/kg. A reduction in the
concentration of leukocytes in the peripheral blood was seen at all doses at
26 weeks and was dose related in females but not in males. At 52 weeks, the
decrease in leukocytes was statistically significant compared with controls in males
but not in females. These differences were due to lower concentrations of
neutrophils or lymphocytes with occasional effects on monocytes and large
unstained cells, with no consistent pattern of changes in leukocytes. In addition,
evidence of neurobehavioural effects (higher low- and high-beam motor activity)
was seen in the male rats at 18 000 mg/kg. In the absence of other evidence for an
effect on the nervous system, this higher level of exploratory behaviour was
considered of doubtful association with treatment and not indicative of neurotoxicity.
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.
A range of studies in vitro (bacterial mutation, cytogenetics and gene
mutation in mouse lymphoma cells) with ethyl lauroyl arginate and N -lauroyl-Larginine
did not provide evidence of genotoxicity.
In two studies of reproductive toxicity in rats, ethyl lauroyl arginate at a dietary
concentration of 15 000 mg/kg delayed vaginal opening by 4 days in the female
offspring. Although this effect was not accompanied by functional changes, the
Committee considered this effect to be potentially adverse and concluded that the
NOAEL for the dams was a dietary concentration of 6000 mg/kg, corresponding to
502 mg/kg bw per day expressed as ethyl lauroyl arginate, or 442 mg/kg bw per day