title: Free radical metabolism of methyleugenol and related compounds.
abstract: Methyleugenol, the methyl ether of eugenol, both of which are flavorant constituents of spices, has been listed by the National Toxicology Program's Report on Carcinogens as reasonably anticipated to be a human carcinogen. This finding is based on the observation of increased incidence of malignant tumors at multiple tissue sites in experimental animals of different species. By contrast, eugenol is not listed. In this study, we show that both methyleugenol and eugenol readily undergo peroxidative metabolism in vitro to form free radicals with large hyperfine interactions of the methylene allylic hydrogen atoms. These large hyperfine splittings indicate large electron densities adjacent to those hydrogen atoms. Methyleugenol undergoes autoxidation such that the commercial product contains 10-30 mg/L hydroperoxide and is capable of activating peroxidases without the presence of added hydrogen peroxide. Additionally, the hydroperoxide is not a good substrate for catalase, which demonstrates that these antioxidant defenses will not be effective in protecting against methyleugenol exposure.
authors.affiliation: Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health , P.O. Box 12233, Research Triangle Park, North Carolina 27709, United States.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Sipe
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Lardinois
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D005054:Eugenol / Q000031:analogs & derivatives* / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D013056:Spectrophotometry, Ultraviolet
chemical_list: D005609:Free Radicals; C005223:methyleugenol; D005054:Eugenol