3.1.1. Alkenylbenzene Derivatives

*Alkenylbenzene* (AB) compounds (Figure 1(1–6)) are important constituents of herbs and spices such as nutmeg (*Myristica fragrans*), cinnamon (*Cinnamomum verum*), anise star (*Illicium verum*), tarragon (*Artemisia dracunculus*), sweet basil (*Ocimum basilicum*), and sweet fennel (*Foeniculum vulgare*) which are present in the modern food chain mainly as a result of use of these herbs and spices and the use of their essential oils as flavorings [76]. There are two general types of ABs, methylenedioxyallylbenzenes and methoxyallylbenzenes [77,78], with different potential for bioactivation.

ABs are well absorbed following oral intake [79]. Biotransformation pathways are influenced by dose; at lower doses, ring oxidation occurs, whereas, at higher doses, the allyl side chain is also oxidized ultimately through sulfate ester formation to chemically reactive intermediates [78–82]. Polymorphisms in metabolism and lifestyle differences are likely to influence metabolism of these compounds [83].

Some ABs are DNA-reactive, as shown in a study in mice in which several cola beverages were administered in place of drinking water leading to formation of significant levels of DNA adducts in the livers [84]. These adducts were detected in mice treated with extracts of nutmeg or mace, or myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene), the major spice constituent of nutmeg and smaller amounts of adducts derived from safrole, a minor constituent of nutmeg.

The ABs discussed in this section have exhibited carcinogenic activity in rodents. Other ABs, such as eugenol (Figure 1(4)) and methyl isoeugenol, with structures not conducive to formation of an electrophile have not been found to be carcinogenic under conditions in which related ABs with structures that form electrophiles were [78,82,85,86].
