Safety evaluation of certain food additives - ipcs inchem

ALIPHATIC BRANCHED-CHAIN SATURATED AND UNSATURATED ALCOHOLS 313
Table 3 (contd)
No. Flavouring agent Species; sex LD50
(mg/kg bw)
1834 Methyl 2-methyl-2-propenoate Guinea-pigs;
M, F
Reference
5897 b Spealman et al. (1945)
1834 Methyl 2-methyl-2-propenoate Dogs; M, F 4680 b Spealman et al. (1945)
F, female; M, male; NR, not reported.
a Calculated using density of 0.91 g/ml for (E,Z)-3,7,11-trimethyldodeca-2,6,10-trienyl
acetate as reported in Ward (1976).
b Calculated using density of 0.936 g/ml for methyl 2-methyl-2-propenoate as reported in
Deichmann (1941).
(b) Short-term and long-term studies of toxicity
Only for 1 of the 20 substances in this group have studies of short-term
and long-term toxicity been reported. The results of these studies with methyl
2-methyl-2-propenoate (No. 1834) are summarized in Table 4 and described below.
No additional studies of short-term or long-term toxicity on any of the related
substances have become available since their previous evaluation (Annex 1,
reference 167).
Groups of 20 male Wistar rats were administered methyl 2-methyl-
2-propenoate via gavage (vehicle not indicated) at a dose of 0 or 8 mmol/kg bw
(equivalent to approximately 800 mg/kg bw) for 30 consecutive days (Bereznowski,
1995). Body weight, food intake and water consumption were measured daily. At
the end of the study, blood samples were taken for analysis in enzyme assays
(serum alanine aminotransferase activity and other unspecified enzymes) and in
assays to determine bilirubin and protein concentration. Tissues and organs were
weighed and prepared for light microscopy.
No effects were seen on food consumption, serum analyses, body weight,
organ to body weight ratios or enzyme levels. Upon histopathological examination,
no abnormalities or lesions appeared in the examined organs (liver, spleen, kidney,
lung, heart, intestine and brain) (Bereznowski, 1995). The no-observed-effect level
(NOEL) is 800 mg/kg bw per day, the highest dose tested. The Committee, however,
noted the limited reporting of this study and that the examinations performed were
limited when compared with the requirements in current test guidelines for shortterm
studies of toxicity.
In a 2-year study of long-term toxicity (Borzelleca et al., 1964), methyl
2-methyl-2-propenoate was added to the drinking-water of groups of 25 male and
25 female Wistar rats at concentrations of 0, 6, 60 or 2000 mg/l. After 4 months of
treatment, the low and medium concentrations were increased to 7 and 70 mg/l,
respectively. Based on the average water intake over the whole study and assuming
an average body weight of 400 g for males and 250 g for females throughout the
study, these concentrations in drinking-water correspond to calculated intakes of
approximately 0, 0.6, 6 and 160 mg/kg bw per day for male rats and 0, 0.9, 9 and