Safety evaluation of certain food additives - ipcs inchem

SUBSTANCES STRUCTURALLY RELATED TO MENTHOL (addendum) 589
Table 3. Results of oral acute toxicity studies with substances related to
menthol used as flavouring agents
No. Flavouring agent Species; sex LD50
(mg/kg bw)
(b) Short-term studies of toxicity
Results of short-term studies of toxicity are available only for menthyl
pyrrolidone carboxylate (No. 1858). They are summarized in Table 4 and described
below.
Table 4. Results of short-term studies of toxicity with substances structurally
related to menthol used as flavouring agents
No. Flavouring agent Species;
sex
1858 Menthyl pyrrolidone
carboxylate
1858 Menthyl pyrrolidone
carboxylate
No. of test
groups a /no.
per group b
Route Duration
(days)
NOAEL
(mg/kg
bw per
day)
Rat; M, F 4/20 Diet 21 610 (M)
620 (F)
Rat; M, F 4/20 Diet 90 109 (M)
127 (F)
F, female; M, male; NOAEL, no-observed-adverse-effect level.
a Total number of test groups does not include control animals.
b Total number per test group includes both male and female animals.
(i) Menthyl pyrrolidone carboxylate (No. 1858)
References
1853 2-(l-Menthoxy)ethanol Rat; M,F >2000 Shirai (2003)
1854 l-Menthyl acetoacetate Rat; M, F >5000 Moreno (1977)
1858 Menthyl pyrrolidone carboxylate Mouse; M, F 4500 Fairey (1977a)
1858 Menthyl pyrrolidone carboxylate Mouse; M, F 5200 Fairey (1977b)
1858 Menthyl pyrrolidone carboxylate Rat; M, F 9600 Edwards et al.
(1977a)
F, female; M, male.
References
Edwards et
al. (1977a)
Edwards et
al. (1977b)
Groups of 4-week-old Colworth Wistar rats (eight per sex per dose) were fed
0, 0.1, 0.5, 1 or 2% menthyl pyrrolidone carboxylate in the diet for 3 weeks. These
dietary levels were equivalent to daily intakes of 0, 120, 610, 1210 or 2390 mg/kg
bw per day for males and 0, 130, 620, 1280 or 2530 mg/kg bw per day for females.
Food and water intake and individual body weights were recorded weekly. At
necropsy, haematological, serum biochemical and urine analyses were conducted.
Select organs (e.g. brain, spleen, heart, kidney, liver, adrenals and testes) were
weighed, and tissue samples were prepared for histological evaluation. One female