Safety evaluation of certain food additives - ipcs inchem

ETHYL LAUROYL ARGINATE 63
treatment groups. There were no other significant clinical signs reported in any of
the animals. Body weight, body weight gain and food consumption were unaffected
by treatment, apart from the one female in the 200 mg/kg bw per day dose group
(discussed above). There were no treatment-related findings at necropsy. Two
females, one in each of the groups receiving 200 and 2000 mg/kg bw per day,
showed high pre-implantation losses; however, because these losses were deemed
by the authors to have occurred before the start of treatment, these two incidences
were considered not to be related to treatment. The group mean value for postimplantation
loss was higher in animals receiving 600 mg/kg bw per day (8%)
compared with other groups (1–3%); however, in the absence of a similar effect in
the top dose group, the authors considered this to be unrelated to treatment. There
were no treatment-related effects on fetal survival or development.
The authors concluded that ethyl lauroyl arginate at doses up to 2000 mg/
kg bw per day during days 6–19 of gestation had no significant effects on dams or
on the survival and development of their fetuses. A high dose level of 2000 mg ethyl
lauroyl arginate/kg bw per day (equal to 1382 mg ethyl-N -lauroyl-L-arginate HCl/
kg bw per day) was considered to be the maximum suitable dose for a subsequent
embryo-fetal study (Huntingdon Life Sciences Ltd, 1998b).
In the main embryo-fetal toxicity study, four groups of 22 pregnant female
rats (Sprague-Dawley CD) were administered ethyl lauroyl arginate (purity, 69.1%
ethyl-N -lauroyl-L-arginate HCl) by gavage at concentrations of 0, 200, 600 or
2000 mg/kg bw per day during days 6–19 of gestation. This study was conducted
in accordance with GLP and OECD guidelines. Allowing for the composition of the
test material, the doses were equal to 0, 138, 415 and 1382 mg ethyl-N -lauroyl-Larginate
HCl/kg bw per day. All animals were observed at least twice daily
throughout the study for clinical condition and signs of reaction to treatment. Body
weight and food consumption were recorded at regular intervals throughout the
study. On gestation day 20, females were culled and examined macroscopically.
The reproductive tract was dissected, and the following were recorded: weight of
gravid uterus, number of corpora lutea in each ovary, number of implantation sites,
number of resorption sites, and number and distribution of fetuses in each uterine
horn. In addition, fetal examinations were performed (body weight, sex, external and
internal abnormalities, placental weight).
Three females receiving 2000 mg/kg bw per day were killed in extremis on
day 7 or 8 of gestation, after 2 or 3 days of dosing. All three animals had noisy and
gasping respiration and salivation after dosing. Two of the females showed
significant body weight loss before termination, and one of these two showed signs
of underactive behaviour and piloerection. Necropsy of all three animals revealed
large amounts of gaseous material in the gastrointestinal tract, particularly the
stomach. Other necropsy findings observed in some of these three animals included
enlarged and prominent lymph nodes, haemorrhagic lungs, large amounts of pale
yellow viscous material in the ileum, reduced and hydrated caecal contents, dark
and enlarged adrenals and a pronounced internal structure of the kidneys. All of
these three females were pregnant, and implantation sites were normal. In addition,
two females receiving 600 mg/kg bw per day were similarly affected towards the
end of gestation, both showing signs of noisy respiration, salivation at the time of