Safety evaluation of certain food additives - ipcs inchem

FURAN-SUBSTITUTED ALIPHATIC HYDROCARBONS 501
that were administered [ 14 C]furan, supporting a non-genotoxic mechanism of
hepatocarcinogenicity (Burka et al., 1991; Byrns et al., 2006). The furan derivatives
described in this monograph are used as flavouring substances at levels that are
orders of magnitude below the levels of furan administered in the 2-year bioassay.
Additionally, the non-genotoxic mechanism of action by furan through an
enedialdehyde metabolite is the principal metabolic pathway available to furan. The
substituted furan derivatives have additional metabolic options available to them
that prevent high concentrations of enedialdehyde metabolites from forming.
2.2 Toxicological studies
2.2.1 Acute toxicity
Oral median lethal doses (LD50 values) have been reported for 10 of the 40
flavouring agents in this group (see Table 2). In rats, LD50 values are in the range
from 138 to 4458 mg/kg bw, demonstrating that the oral acute toxicity of furansubstituted
aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids
and related esters, sulfides, disulfides and ethers is low (Long, 1977a, 1977b;
Moreno, 1977; Gabriel, 1979; Moran et al., 1980; Piccirillo et al., 1982, 1983a,
1983b; Reagan & Becci, 1984a, 1984b; Burdock & Ford, 1990a, 1990b, 1990c,
1990d). In mice, oral LD50 values ranged from 438 mg/kg bw for 2-acetyl-5methylfuran
(No. 1504) to 1220 mg/kg bw for 2-pentylfuran (No. 1491)
(Shellenberger, 1971a; Griffiths & Babish, 1978; Moran et al., 1980).
Table 2. Results of oral acute toxicity studies with furan-substituted aliphatic
hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related
esters, sulfides, disulfides and ethers used as flavouring agents
No. Flavouring agent Species; sex LD50
(mg/kg bw)
1491 2-Pentylfuran Mice; M, F 1185 (M)
1220 (F)
References
Shellenberger
(1971a)
1491 2-Pentylfuran Mice; M, F 1200 Moran et al.
(1980)
1494 3-Methyl-2-(3-methylbut-2-enyl)-furan Rats; M 660 Gabriel (1979)
1495 2,3-Dimethyl-benzofuran Rats; M, F 1952 Long (1977a)
1497 3-(2-Furyl)acrolein Rats; M, F >900 (M)
>857 (F)
1497 3-(2-Furyl)acrolein Rats; M, F >900 (M)
>860 (F)
Piccirillo et al.
(1983a)
Burdock & Ford
(1990a)
1498 2-Methyl-3(2-furyl)acrolein Rats; M, F 1400 Reagan & Becci
(1984a)