Safety evaluation of certain food additives - ipcs inchem

ALIPHATIC BRANCHED-CHAIN SATURATED AND UNSATURATED ALCOHOLS 325
(ii) In vivo
In an in vivo replicative DNA synthesis study, weanling B6C3F1 mice were
administered a single dose of methyl 2-methyl-2-propenoate (No. 1834) at 0, 1000
or 2000 mg/kg bw via gavage. At 24, 39 and 48 h, hepatocytes were harvested and
examined. No DNA synthesis was noted at either dose level (Miyagawa et al., 1995).
Groups of six mice were orally administered methyl 2-methyl-2-propenoate
(range 1.13–4.52 g/kg) as part of a micronucleus test. The highest dose, split into
four equal amounts, was administered to an additional group of five mice. Frequency
of reticulocytes, the number of erythrocytes observed and the number of
micronucleated erythrocytes were recorded. There were no differences from
controls (Hachitani et al., 1982).
The International Agency for Research on Cancer (1994) reported that
methyl 2-methyl-2-propenoate induced chromosomal aberrations in rat bone
marrow cells (Fedyukovich & Egorova, 1991) but not micronuclei in mouse bone
marrow cells (Hachitani et al., 1981) after intraperitoneal injection. The European
Food Safety Authority (2008) reported negative results in a dominant lethal assay
in mice (ICI, 1976b) and a chromosomal aberration test in humans (Seiji et al.,
1994), both following inhalation exposure to methyl 2-methyl-2-propenoate.
(iii) Conclusion
(±)-Dihydrofarnesol (No. 1830) was found to be not mutagenic in Ames
assays with S. typhimurium and E. coli, with and without metabolic activation. Also,
methyl 2-methyl-2-propenoate (No. 1834) tested for the most part negative in Ames
assays with S. typhimurium, with and without metabolic activation. Methyl 2methyl-2-propenoate
induced micronuclei, chromosomal aberrations and sister
chromatid exchanges in several mammalian cell lines, predominantly at doses with
cytotoxic effects. However, in in vivo studies, methyl 2-methyl-2-propenoate did not
induce replicative DNA synthesis or micronuclei in mice after oral administration or
dominant lethal mutations in mice or chromosomal aberrations in humans after
inhalation. Following intraperitoneal injection, methyl 2-methyl-2-propenoate
induced chromosomal aberrations in rats but not micronuclei in mice. Considering
all available data, the Committee concluded that there is no convincing evidence
that members of this group of aliphatic branched-chain saturated and unsaturated
alcohols, aldehydes, acids and related esters exhibit significant genotoxic potential
in vivo.
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