Safety evaluation of certain food additives - ipcs inchem

550 MISCELLANEOUS NITROGEN-CONTAINING SUBSTANCES (addendum)
concluded to be of no safety concern based on current estimated levels of intake;
however, the evaluation was conditional for 10 of these substances, because the
estimated exposure was based on anticipated annual volumes of production. At the
present meeting, actual volumes of production for these substances were provided,
and the Committee confirmed that these 10 substances were of no safety concern
based on current estimated levels of intake.
Twelve of the 14 substances (Nos 1884–1890, 1892–1894, 1896 and 1897)
have been reported to occur naturally in foods. They have been detected in
cabbages, radish, mustards, wasabi, garlic, bread, milk and wines (Nijssen et al.,
2007).
1.2 Assessment of dietary exposure
The total annual volume of production of the 14 flavouring agents in this
group is approximately 913 kg in Japan (Japan Flavor & Fragrance Materials
Association, 2002). More than 54% of the total annual volume of production in
Japan is accounted for by a single substance in this group—namely, 4-pentenyl
isothiocyanate (No. 1893), which has an estimated per capita intake of 132 μg/
person per day. More than 37% of the total annual volume of production is
accounted for by two other substances in this group—namely, 3-butenyl
isothiocyanate (No. 1889) and 5-hexenyl isothiocyanate (No. 1894), which have
estimated per capita intakes of 50 and 40 μg/person per day, respectively. The
estimated per capita intakes of all the other flavouring agents in the group range
from 0.03 to 12 μg/person per day (Japan Flavor & Fragrance Materials Association,
2002), with most of the intake values at the lower end of this range. The estimated
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
Isothiocyanates are readily absorbed and distributed to all major tissues in
studies in rodents. Peak concentrations in these tissues are achieved between 2
and 8 h after dosing. Metabolic studies in humans, mice and rats indicate that
isothiocyanates react readily with reduced glutathione (GSH) to form a conjugate
as the primary metabolite and that the reaction is catalysed enzymatically by
glutathione S-transferase, although a slower non-enzymatic reaction can also
occur. Both reactions occur in a pH-dependent equilibrium. In rats, the Nacetylcysteine
conjugates appear as the major metabolites in urine, whereas some
isothiocyanate–GSH conjugates are excreted into bile.