Distribution and metabolism of (5-hydroxymethyl)furfural in male F344 ratsand B6C3F1 mice after oral administration

(5-Hydroxymethyl)furfural (HMF), a heat-induced decomposition product of he xoses, is present in food and drink. Recent reports have shown HMF to be an in vitro mutagen after sulfate conjugation and to be a promoter as well as a weak initiator of colonic aberrant foci in rats, in order to investigate the metabolic activation further and to provide information for HMF toxico logy studies, the disposition of [C-14]-HMF has been investigated in male F 344 rats and B6C3F1 mice following po administration of either 5, 10, 100, or 500 mg/kg. Tissue distribution results indicated that absorption of HMF was rapid in male rats and mice and that tissue concentrations in male mice at the earliest time point are not linearly proportional to dose. Excretio n was primarily via the urine in both, with 60-80% of the administered dose excreted by this route in 48 h. Tissue/blood ratios of HMF-derived radioac tivity were greater than I for liver and kidney. Three metabolites were ide ntified and quantitated in urine. Formation of one of the metabolites, N-(5 -hydroxymethyl-2-furoyl)glycine, was inversely proportional to dose in rats but not mice. None of the metabolites were sulfate conjugates nor likely t o be formed from sulfate conjugates. There were relatively low levels of no nextractable radioactivity in liver, kidney, and intestines, indicating tha t some reactive intermediate(s) may be formed.