Safety evaluation of certain food additives - ipcs inchem

314 ALIPHATIC BRANCHED-CHAIN SATURATED AND UNSATURATED ALCOHOLS
Table 4. Results of studies of short-term and long-term toxicity with aliphatic
branched-chain saturated and unsaturated alcohols, aldehydes, acids and
related esters
No. Flavouring
agent
Species;
sex
Short-term studies of toxicity
1834 Methyl 2methyl-2propenoate
Long-term studies of toxicity
1834 Methyl 2methyl-2propenoate
1834 Methyl 2methyl-2propenoate
No. of
test
groups a /
no. per
group b
Route Duration NOEL
(mg/kg
bw per
day)
Reference
Rats; M 1/20 Gavage 30 days 800 c Bereznowski
(1995)
Rats;
M, F
Dogs;
M, F
3/50 Drinkingwater
3/4 Capsule,
via diet
2 years M: 160d F: 200d Borzelleca et
al. (1964)
2 years 37.5 d Borzelleca et al.
(1964)
F, female; M, male; NOEL, no-observed-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.
c Only one dose level was tested. As this dose produced no adverse effects, it is not a true
NOEL, but the highest dose tested that had no adverse effects. The actual no-observed-
(adverse-)effect level, or NO(A)EL, may be higher.
d This highest dose level produced no adverse effects. It is therefore not a true NOEL. The
actual NO(A)EL may be higher.
200 mg/kg bw per day for female rats, respectively. Food and treated drinking-water
were available ad libitum. Body weights were recorded weekly. Water and food
consumption were determined over a 3-day period at the end of weeks 1 and 4, on
a monthly basis during months 2–6 and every other month to the end of the study
after month 6. At 3-month intervals, blood samples and pooled urine samples were
taken from five rats per sex per dose for haematological examinations (haematocrit,
haemoglobin, total and differential white blood cell count) and urinalysis (protein and
reducing substances). At termination of the study, all surviving animals were
sacrificed. Organ weights of heart, spleen, kidney, liver and testes were recorded.
Samples from some 15 tissues and organs (including liver, kidney, spleen and brain)
were preserved, and histopathological examinations were performed on samples
taken from all rats except those in the lowest treatment group.
There was no difference in survival between treated and control animals.
Aside from a slight reduction in body weight in high-dose animals during the first
few weeks of treatment, no changes in body weight were observed. Food
consumption was not affected by treatment, but water consumption was statistically