Safety evaluation of certain food additives - ipcs inchem

386 ALKOXY-SUBSTITUTED ALLYLBENZENES
Table 3 (contd)
No. Flavouring
agent
1790 Methyl
eugenol
Species;
sex
Rats;
M, F
No. of
test
groups a /
no. per
group b
Route Duration
(days)
NOEL c /
NOAEL d
(mg/kg bw
per day)
Reference
4/100 Gavage 730 37 d,e,j National
Toxicology
Program
(2000)
1792 Safrole Mouse; F Diet 600 150–300 d,e Miller et al.
(1983)
1792 Safrole Mouse;
M, F
1792 Safrole Mouse;
M, F
1/104 Gavage 420 370 d,e,i Miller et al.
(1983)
2/36 Gavage;
diet
574 1265 d,e,k Borchert
et al. (1973)
1792 Safrole Mouse; M 1/10 Diet 525 400 d,e Lipsky et al.
(1981a,
1981b,
1981c)
1792 Safrole Dog; M, F 2/4 Oral 2190 5 d,e Hagan et al.
(1967)
1792 Safrole Rat; M, F 4/20 Diet 730 50 d,e Hagan et al.
(1967)
1792 Safrole Rat; M, F 4/50 Diet 730 25 d Long et al.
(1963)
F, female; M, male.
a Total number of test groups does not include control animals.
b Total number per test group includes both male and female animals.
c No-observed-effect level.
d No-observed-adverse-effect level.
e Study performed with either a single dose or multiple doses that produced adverse effects.
The value is therefore not a true NOAEL, but is the lowest dose level tested that produced
adverse effects. The actual NOAEL may be lower.
f Nutmeg oil tested (approximately 7% myristicin).
g Nutmeg oil tested (approximately 1.3% safrole).
h To avoid intolerance, the dietary concentration was reduced by 75% for the first 10 days
and 50% for the next 10 days. The target diet was then maintained for 12 months.
i Dosage administered via gavage twice a week for 10 doses; mice were evaluated for
14 months.
j Stop-exposure groups received 300 mg/kg doses for 53 weeks followed by the vehicle only
(0.5% methylcellulose) for the duration of the study.
k Mice were administered safrole by stomach tube for 21 days (464 mg/kg bw), followed by
dietary administration (1112 mg/kg bw) for 82 weeks.