The metabolic fate of a compound is
determined by numerous factors including its chemical
structure. Although the metabolic options for a variety of
functional groups are well understood and can often provide a
rationale for the comparison of toxicity based on structural
analogy, at times quite minor structural variations may have
major consequences for metabolic outcomes and toxicity. In this perspective, the effects of structural variations on metabolic
outcomes is detailed for a group of related hydroxy- and alkoxy-substituted allyl- and propenylbenzenes. These classes of
compounds are naturally occurring constituents of a variety of botanical-based food items. The classes vary from one another by
the presence or absence of alkylation of their para-hydroxyl substituents and/or the position of the double bond in the alkyl side
chain. We provide an overview of how these subtle structural variations alter the metabolism of these important food-borne
compounds, ultimately influencing their toxicity, particularly their DNA reactivity and carcinogenic potential. The data reveal that
detailed knowledge of the consequences of subtle structural variations for metabolism is essential for adequate comparison of
structurally related chemicals. Taken together, it is concluded that predictions in toxicological risk assessment should not be
performed on the basis of structural analogy only but should include an analogy of metabolic pathways across compounds and