The metabolic disposition of [methoxy-¹⁴C]-labelled trans-anethole, estragole and p-propylanisole in human volunteers

Abstract

1. The metabolic fates of the naturally occurring food flavours trans-anethole and estragole, and their synthetic congener p-propylanisole, have been investigated in human volunteers using the [methoxy-¹⁴C]-labelled compounds. The doses used were close to those encountered in the diet, 1 mg, 100μg and 100 μg 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.