Safety evaluation of certain food additives - ipcs inchem

58 ETHYL LAUROYL ARGINATE
the results of the 13-week dietary study described above (Huntingdon Life Sciences
Ltd, 2001c) in which a NOAEL of 5000 mg ethyl lauroyl arginate/kg diet (equal to
384 mg ethyl lauroyl arginate/kg bw per day) was identified. Groups of eight male
and eight female rats were allowed free access to the diets for 4 weeks prior to
pairing for mating. Treatment was then continued throughout mating and until
termination after weaning of the litters. The animals selected to form the F1
generation were continuously treated with diets at concentrations of 0, 1500, 5000
or 15 000 mg/kg (equal to 0, 173, 589 and 1750 mg/kg bw per day for males; and
0, 169, 586 and 1734 mg/kg bw per day for females) from the time of weaning until
termination at 8 weeks of age.
All animals were checked at least twice daily for clinical signs; once a week,
animals were subjected to a thorough physical examination. Body weight and food
consumption were recorded at regular intervals for both the F0 and F1 animals. After
the initial 4 weeks of treatment, F0 females were paired on a one-to-one basis with
males from the same treatment group. Mating was ascertained by vaginal smears
and ejected copulation plugs, and the day on which mating was detected was
designated day 0 of gestation. Once mating had occurred, the males and females
were separated. All F0 females were allowed to deliver their young naturally and
rear their own offspring until day 21 of lactation. All litters were examined at day 1
of age for numbers of live and dead pups, body weights, sex ratio and general
clinical observations; and subsequently examined daily for clinical signs and dam/
litter interaction until day 21 of age. Following weaning, offspring were selected for
the F1 generation based on a random numbers table (12 males and 12 females per
treatment group). Sexual maturation was assessed for the selected F1 males and
females, and body weights were recorded twice weekly.
F0 males were culled after successful littering by females, and F0 females
were culled after their litters were weaned. All F0 animals were subjected to a
detailed macroscopic examination, and samples of any abnormal tissues were
taken. The number of implantation sites was recorded for F0 females. All F1 animals
were subjected to a detailed macroscopic examination.
The general condition of treated F0 and F1 animals was similar to that of
controls, and no deaths occurred. Body weight and body weight gain of F0 males
and females were not adversely affected by treatment. Body weight of F1 males and
females and body weight gain to 8 weeks of age were unaffected by treatment. Food
consumption was similar in all groups of F0 animals, both before mating and, for
females, during gestation and lactation. Food consumption of F1 animals was similar
to that of controls, and there were no clear effects on food conversion efficiency in
F0 animals in the pre-pairing period or in the F1 animals up to 8 weeks of age. In the
F0 females, the intakes of ethyl lauroyl arginate increased during lactation in
response to the physiological demands of the litter, reaching a level of approximately
twice the premating intake during the 2nd week of lactation. F1 animals had higher
intakes of ethyl lauroyl arginate than did their F0 parents, as expected based on the
higher food consumption of young animals. Mating performance, fertility, gestation
length, gestation index, numbers of implantations and litter sizes were similar in all
groups and were considered to be unaffected by treatment up to 15 000 mg/kg diet.
At 15 000 mg/kg diet, the litters of two of the eight females lost body weight in the