Safety evaluation of certain food additives - ipcs inchem

ALKOXY-SUBSTITUTED ALLYLBENZENES 391
Groups of 10 male and 10 female F344 rats were administered methyl
eugenol in 0.5% methylcellulose at 0 (control), 10, 30, 100, 300 or 1000 mg/kg bw
by gavage, 5 days a week, for 14 weeks. The final mean body weight gains of males
receiving 300 and 1000 mg/kg bw per day and of all the dosed females were
significantly (P = 0.01) less than those of the vehicle controls. Liver weights in male
rats dosed with 100 mg/kg bw per day and in female rats dosed with 300 mg/kg
bw per day were significantly higher than those of the control rats. Relative liver
weights of male rats at 30 mg/kg bw per day were increased compared with the
vehicle controls, but not with respect to the untreated controls. A significant increase
in testis weight was observed in male rats receiving 1000 mg/kg bw per day.
Haematological examination revealed a decreased mean packed red cell volume
in male rats at the 300 mg/kg bw per day level and in male and female rats at the
1000 mg/kg bw per day level. There were also increased platelet counts and
increased blood ALT and sorbitol dehydrogenase activities in male and female
rats receiving 100 mg/kg bw per day. Additionally, hypoproteinaemia,
hypoalbuminaemia and increased bile acid concentrations were evident in males
and females receiving 300 mg/kg bw per day. An increase in the incidence of
adrenal gland cortical hypertrophy and cytoplasmic alteration in the submandibular
gland occurred at the 100 mg/kg bw per day or higher levels in male and female
rats. Atrophy and chronic inflammation (chronic gastritis) of the glandular stomach
mucosa were increased in male and female rats administered 300 mg/kg bw or
greater, and there was a hepatocellular adenoma in one male rat administered
1000 mg/kg bw per day. There were no significant findings at the 30 mg/kg bw per
day dose level (National Toxicology Program, 2000).
(d) Myristicin (No. 1791)
(i) Rats
Twelve male white rats (strain not specified) were administered 10 mg
myristicin/kg bw daily in food for 26 days. There were no differences in body weights
between the animals receiving myristicin and the controls. Histological studies of
livers and kidneys showed no abnormalities that could be attributed to myristicin
administration (Truitt et al., 1961).
(e) Safrole (No. 1792)
(i) Rats
Groups of 10 male and female Osborne-Mendel rats were administered
safrole by oral intubation at doses of 250, 500 and 750 mg/kg bw per day for various
durations. At doses of 750 mg/kg bw per day for 19 days, 9/10 animals died; at
500 mg/kg bw per day, 1/10 animals died after 46 days; at 250 mg/kg bw per day,
no animals died within 34 days, and the following effects were observed: liver
hypertrophy with focal necrosis plus slight fibrosis, fatty infiltration (steatosis) and
bile duct proliferation, along with adrenal enlargement with fatty infiltration (Hagan
et al., 1965).