Safety evaluation of certain food additives - ipcs inchem

534 HYDROXY- AND ALKOXY-SUBSTITUTED BENZYL DERIVATIVES (addendum)
was evaluated at the eleventh meeting of the Committee (Annex 1, reference 14),
and a conditional acceptable daily intake (ADI) 1 of 0–10 mg/kg body weight (bw) per
day was assigned. At its thirty-fifth meeting (Annex 1, reference 88), the Committee
converted the conditional ADI to a temporary ADI of 0–5 mg/kg bw per day. At its
thirty-ninth meeting (Annex 1, reference 101), the Committee extended the
temporary ADI of 0–5 mg/kg bw per day. At its forty-fourth meeting (Annex 1,
reference 116), the Committee established an ADI of 0–3 mg/kg bw per day. Vanillin
was evaluated at the eleventh meeting of the Committee and assigned an ADI of
0–10 mg/kg bw per day. Methyl salicylate was evaluated at the eleventh meeting of
the Committee, and an ADI of 0–0.5 mg/kg bw per day was assigned. Piperonal
was evaluated at the eleventh meeting of the Committee and assigned an ADI of
0–2.5 mg/kg bw per day. All other members of this group were evaluated by the
Procedure and concluded to be of no safety concern based on current estimated
levels of intake.
Two of the six flavouring agents in this group are natural components of food
(Nos 1878 and 1881). They have been detected in a variety of fruits, types of honey
and alcoholic beverages, but quantitative data on natural occurrence were not
available (Gatfield, 2006; Nijssen et al., 2007).
1.2 Assessment of dietary exposure
The total annual production volume of the six hydroxy- and alkoxysubstituted
benzyl derivatives is approximately 822 kg in Europe (European Flavour
and Fragrance Association, 2005), 61 kg in the USA (Gavin et al., 2007) and
204 kg in Japan (Japan Flavor & Fragrance Materials Association, 2002). More
than 99% of the annual production volume in Europe and Japan is accounted for
by vanillin propylene glycol acetal (No. 1882). More than 85% of the annual production
volume in the USA is accounted for by sodium 4-methoxybenzoyloxyacetate
(No. 1880) and 4-methoxybenzoyloxyacetic acid (No. 1883). The daily per capita
intake of each flavouring 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
The hydrolysis of aromatic acetals in simulated gastric juice and intestinal
fluid supports the conclusion that the acetal functional group is hydrolysed before
absorption in vivo. Both vanillin 3-(l-menthoxy)propane-1,2-diol acetal (No. 1879)
and vanillin propylene glycol acetal (No. 1882) undergo hydrolysis under acidic
conditions to form the corresponding alcohol and aldehyde, which will be rapidly
metabolized and eliminated. The resulting hydroxy- and alkoxy-substituted
derivatives are rapidly absorbed from the intestine, metabolized in the liver and
excreted unchanged or as sulfate or glucuronide conjugates. Minor metabolic
pathways include O-demethylation, reduction and/or decarboxylation.
1 “Conditional ADI”, which signifies an ADI with special considerations, is a term no longer
used by the Joint FAO/WHO Expert Committee on Food Additives.