The metabolic disposition of methoxy carbon 14 labelled trans anethole estragole and p propylanisole in human volunteers

Sangster S. A.; Caldwell J.; Hutt A. J.; Anthony A.; Smith R. L.

1. The metabolic fates of the naturally occurring food flavors trans-anethole and estragole, and their synthetic congener p-propylanisole have been investigated in human volunteers using the [methoxy-14C]-labeled compounds. The doses used were close to those encountered in the diet, 1 mg, 100 .mu.g and 100 .mu.g respectively. 2. In each case, the major routes of elimination of 14C were in the urine and in the expired air as 14CO2. 3. Urinary metabolites were separated by solvent extraction, t.l.c. and h.p.l.c., and characterized by comparison of chromatographic mobilities with standards and by radioisotope dilution. Nine 14C urinary metabolites were found after trans-anethole administration, four after p-propylanisole and five after estragole. All were products of side chain oxidations. 4. The principal metabolites of p-propylanisole were 4-methoxyhippuric acid (12%) and 1-(4'-methoxyphenyl)propan-1-ol (2%) and -2-ol (8%). 5. The major metabolite of trans-anethole was 4-methoxyhippuric acid (56% of dose), accompanied by much smaller amounts of the two isomers of 1-(4'-methoxyphenyl)propane-1,2-diol (together 3%). 6. After estragole administration, the two volunteers eliminated 0.2 and 0.4% of the dose respectively as 1'-hydroxyestragole. 7. The human metabolic data is discussed with reference to the comparative metabolic disposition of these compounds in the mouse and rat, species commonly used in their safety assessment.