Influence of dose size on the disposition of trans-[methoxy-14C]anethole in human volunteers.

The influence of dose size on the metabolic fate of the naturally occurring food flavouring trans-anethole has been investigated in human volunteers, using the [methoxy-14C]-labelled compound. The doses chosen were: 1 mg; close to the daily intake in the diet from foods, 50 mg; approximating to the amount present in a normal measure of an anise-flavoured beverage, and 250 mg. The order of administration was randomized. The major routes of elimination of 14C were in the urine (54-69% of the administered dose) and as exhaled 14CO2 (13-17%). Dose size had no systematic effect on either rate or route of excretion. Urinary metabolites were separated by high-pressure liquid chromatography, before and after treatment with beta-glucuronidase, and identified by comparison of their chromatographic mobilities with those of authentic standards. The principal metabolite (greater than 90% of urinary 14C) was 4-methoxyhippuric acid, accompanied by much smaller amounts of 4-methoxybenzoic acid and up to three other compounds, which were not examined further. The pattern of urinary metabolites was unaffected by dose size. These data are discussed with reference to the comparative metabolic disposition of trans-anethole in rats and mice, the species commonly used in toxicity testing and in which its fate exhibits a very marked dose dependence.