Metabolism of anethole. I. Pathways of metabolism in the rat and mouse.

The metabolic fate of the naturally occurring food flavouring trans-anethole has been investigated in rats and mice. A single 50-mg/kg dose of trans-[methoxy-14C]anethole was given orally to female Wistar albino rats and by ip injection to male CD-1 mice. The major routes of elimination of 14C were the urine and expired air (as 14CO2). Excretion of 14C in the faeces and as volatile compounds in the expired air was very low (total less than 2% of the dose). Urinary metabolites were separated by solvent extraction, TLC and HPLC and were characterized by MS and GC-MS directly and following methylation or trimethylsilylation, the results being compared where possible with authentic standards. Eleven 14C-containing urinary metabolites were identified in the rat and ten in the mouse. These compounds arose from side-chain oxidation, side-chain cleavage and various conjugations. The major urinary metabolites were two isomers of 1-(4'-methoxyphenyl)propane-1,2-diol, 2-hydroxy-1-methylthio-1-(4'-methoxyphenyl)propane and 4-methoxyhippuric acid, the first three all being excreted as glucuronides. In addition to these 14C-labelled metabolites, 4-hydroxypropenylbenzene, the unlabelled product of oxidative O-demethylation of trans-[14C]anethole, was excreted extensively in urine as the glucuronide.