Safety evaluation of certain food additives - ipcs inchem

ALIPHATIC LINEAR ,-UNSATURATED ALDEHYDES 345
metabolism in the fatty acid pathway or the tricarboxylic acid cycle. These pathways
have a high capacity and would not be saturated, even if all flavouring
agents were consumed at the same time. Most of the substances in this group
that have been evaluated by the Committee at its present meeting and at the sixtythird
meeting are predicted or known to be metabolized to common metabolites.
Common metabolites (and their precursors) are (E)-2-butenoic acid (No. 1371),
(E)-2-pentenoic acid (No. 1804), trans-2-hexenoic acid (No. 1361), (E)-2-heptenoic
acid (No. 1373), (E)-2-octenoic acid (No. 1805), (E)-2-nonenoic acid (No. 1380) and
(E)-2-decenoic acid (No. 1372), all of which are structural class I. When calculating
for each common metabolite the combined intakes 1 in Europe, the USA and Japan
for up to five flavouring agents with the highest intakes (i.e. Nos 1371, 1806 and
1807 for (E)-2-butenoic acid; Nos 1364, 1793, 1795 and 1804 for (E)-2-pentenoic
acid; Nos 1353, 1354, 1355, 1361 and 1801 for trans-2-hexenoic acid; Nos 1360,
1373, 1798 and 1799 for (E)-2-heptenoic acid; Nos 1363, 1367, 1370, 1811 and
1812 for (E)-2-octenoic acid; Nos 1362, 1365, 1369, 1380 and 1813 for (E)-2nonenoic
acid; and Nos 1348, 1349, 1372, 1794 and 1814 for (E)-2-decenoic acid),
they were all below the threshold of concern (i.e. 1800 μg/person per day for
class I). An additional consideration is that these common metabolites are part of a
homologous series of 2-alkenoic acids; the combined intakes of the five flavouring
agents in this homologous series with the highest intakes in Europe, the USA and
Japan (i.e. Nos 1353, 1354, 1355, 1801 and 1813) would not exceed the human
intake threshold of concern (i.e. 1800 μg/person per day for class I). The Committee
concluded that under the conditions of use as flavouring agents, the combined
intakes of the substances leading to a common metabolite would not saturate the
metabolic pathways and the combined intakes would not raise safety concerns.
1.6 Consideration of secondary components
Three members of this group of flavouring agents, trans-2-hexenal glyceryl
acetal (No. 1800), hexyl trans-2-hexenoate (No. 1810) and methyl trans-2octenoate
(No. 1811), have assay values of less than 95%. Information on the
safety of the secondary components of these three compounds is summarized in
Annex 5 (Summary of the safety evaluation of secondary components for flavouring
agents with minimum assay values of less than 95%). The secondary components
of trans-2-hexenal glyceryl acetal, 3-hexenal glyceryl acetal and hexanal glyceryl
acetal, are expected to share the same metabolic fate. The secondary component
of hexyl trans-2-hexenoate, hexyl trans-3-hexenoate, is expected to share the same
metabolic fate as the primary substance, as is the secondary component of methyl
trans-2-octenoate, methyl trans-3-octenoate. None of the secondary components
is considered to present a safety concern at current estimated levels of intake of the
flavouring agents.
1.7 Conclusion
In the previous evaluation of substances in this group, studies of acute
toxicity, short-term studies of toxicity (2–13 weeks), long-term studies of toxicity and
1 Combined intake was calculated on a molar basis relative to the formation of the common
metabolite.