ABSTRACT
2Methyleugenol (MEG), an allylalkoxybenzene compound, produces a favorable taste and elicits a pleasant smell. These properties have promoted its use as a flavoring substance in foods and drinks, as well as an additive in body bath products to enhance their fragrance. MEG, included in the list of generally recognized as safe (GRAS) substances, is found naturally in plants but is also synthetically produced for commercial purposes. It has relatively large production and usage estimates, a regular rate of intake by humans, and is structurally related to other substances shown to possess carcinogenic activity. Recently, 2-year rodent bioassay studies indicated that there was clear evidence of carcinogenic activity for MEG under the conditions used for testing. Organs affected by MEG exposure included the liver, stomach, blood, testes and uterus, kidney, peritoneum, and skin. The MEG-related toxic and pathological findings in these organs, as well as the etiology, are described and reviewed in this chapter. The toxicity of MEG is attributed to the formation of a reactive metabolite. Bioactivation occurs when the liver metabolizes MEG to 1-hydroxymethyleugenol, which is then sulfated to form 1-sulfoxymethyleugenol, a sulfate ester that is unstable. Upon hydrolysis, a carbonium ion intermediate is formed. This highly reactive electrophile combines with proteins and other macromolecules such as DNA, which may progress to cellular damage and genotoxicity. The results from testing MEG in a variety of genotoxic assays are reviewed. In summary, the toxicity spectrum for MEG is dose dependent. Although relatively high doses do not result in sudden and severe life-threatening responses, prolonged exposure to MEG at relatively low doses may produce deleterious toxic and pathological effects.
