Safety evaluation of certain food additives - ipcs inchem

352 ALKOXY-SUBSTITUTED ALLYLBENZENES
In vitro .....................................................................
In vivo ......................................................................
Genotoxicity conclusions ........................................
Comments .................................................................................
Assessment of dietary exposure .........................................
Evaluation of toxicological data ...........................................
Interpretation of carcinogenicity data from studies in
which high doses were administered by gavage ......
Nature of the dose–response relationship for
hepatocarcinogenicity ..............................................
Non-relevance of neuroendocine gastric tumours to
humans ....................................................................
Relevance of the toxicity data to the ingestion
of spices ...................................................................
Epidemiological studies on spice ingestion ...................
Evaluation ..................................................................................
References ................................................................................
Appendix 1: Alkoxy-substituted allylbenzenes in herbs
and spices .............................................................................
1. EXPLANATION
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The common structural features of this group of six substances are an
allylbenzene nucleus and one or more alkoxy ring substituents. All have an alkoxy
substitution at the para position. Three members of the group contain a 3,4methylenedioxy
substituent and may have additional methoxy substituents:
safrole (3,4-methylenedioxyallylbenzene, No. 1792), myristicin (5-methoxy-3,4methylenedioxyallylbenzene,
No. 1791) and apiole (2,5-dimethoxy-3,4methylenedioxyallylbenzene,
No. 1787) (Figure 1). Three other substances contain
only methoxy substituents: estragole (4-methoxyallylbenzene, No. 1789), methyl
eugenol (3,4-dimethoxyallylbenzene, No. 1790) and elemicin (3,4,5trimethoxyallylbenzene,
No. 1788) (Figure 1). Because of the widespread
occurrence of alkoxy-substituted allybenzenes in food, mainly in spices and herbs
but also in certain vegetables and fruits, these substances are referred to by their
common names.
Estragole was reviewed by the Committee at its twenty-third and twenty-fifth
meetings (Annex 1, references 50 and 56), and safrole was reviewed at the fifth and
twenty-fifth meetings (Annex 1, references 5 and 56). For estragole, no acceptable
daily intake (ADI) was allocated at the twenty-fifth meeting, and the Committee
requested additional long-term studies for evaluation of carcinogenic potential. For
safrole, the Committee concluded at its twenty-fifth meeting that flavouring agents
containing safrole or isosafrole as the principal flavour-active ingredient should not
be used as food additives; and that it is not practicable to advocate the
discontinuance of spices containing safrole or isosafrole as minor constituents (e.g.
nutmeg, mace and cinnamon). However, the Committee at that meeting concluded
that when these spices were used, the amounts of safrole and isosafrole in the
finished product should be kept as low as practicable.
Only two of the substances, estragole and methyl eugenol, are used as
flavouring agents intentionally added to compounded flavours. This use is limited
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