Safety evaluation of certain food additives - ipcs inchem

ALIPHATIC BRANCHED-CHAIN SATURATED AND UNSATURATED ALCOHOLS 293
daily per capita intake is the highest for prenyl acetate in the USA (160 μg). For the
other flavouring agents, the estimated daily per capita intakes were in the range of
0.01–68 μg. The estimated daily per capita intake of each agent is reported in
Table 1. Annual volumes of production of this group of flavouring agents are
summarized in Table 2.
1.3 Absorption, distribution, metabolism and elimination
Information on the hydrolysis, absorption, distribution, metabolism and
elimination of flavouring agents belonging to the group of aliphatic branchedchain
saturated and unsaturated alcohols, aldehydes, acids and related esters
has previously been described in the report of the sixty-first meeting (Annex 1,
reference 166). Additional data on the compounds methyl 2-methyl-2-propenoate
(No. 1834) and (E,Z)-phytol (No. 1832) have now been submitted and are in line
with the information described in the report of the sixty-first meeting.
1.4 Application of the Procedure for the Safety Evaluation of Flavouring
Agents
Step A1. In applying the Procedure for the Safety Evaluation of Flavouring Agents to
the 20 flavouring agents in this group of aliphatic branched-chain saturated
and unsaturated alcohols, aldehydes, acids and related esters, the
Committee assigned 19 of these flavouring agents (Nos 1815–1833) to
structural class I and the remaining flavouring agent (No. 1834) to structural
class II (Cramer et al., 1978).
Step A2. All flavouring agents in this group are expected to be metabolized to
innocuous products. The evaluation of all flavouring agents in this group
therefore proceeded via the A-side of the Procedure.
Step A3. The estimated daily per capita intakes of all 19 flavouring agents in structural
class I are below the threshold of concern (i.e. 1800 μg/person per day for
class I). According to the Procedure, the safety of these 19 flavouring agents
raises no concern when they are used at their current estimated levels of
intake.
The estimated daily per capita intake of the flavouring agent in structural
class II (i.e. methyl 2-methyl-2-propenoate, No. 1834; synonym methyl
methacrylate) is below the threshold of concern (i.e. 540 μg/person per day
for class II). However, the Committee noted that there is a structural similarity
between this flavouring agent and ethyl methacrylate, a substance reported
to be neurotoxic. These two chemicals share a common metabolite,
methacrylic acid, which is unlikely to be a neurotoxicant because it is more
polar and therefore less likely to cross the blood–brain barrier. Because
methyl 2-methyl-2-propenoate was shown to have some neurotoxic
properties in rats dosed at 500 mg/kg bw per day by gavage for 21 days, the
Committee decided to apply the threshold of toxicological concern (TTC) for
structural class III (i.e. 90 μg/person per day), which was derived using data
that included neurotoxic compounds. Given that the estimated daily per
capita intake of methyl 2-methyl-2-propenoate is even well below this lower
threshold of concern, the Committee concluded that the safety of this
flavouring agent raises no concern when it is used at its current estimated
level of intake.