DISTRIBUTION AND METABOLISM OF (5-HYDROXYMETHYL)FURFURAL IN MALE F344 RATS AND B6C3F1 MICE AFTER ORAL ADMINISTRATION

(5-Hydroxymethyl)furfural (HMF), a heat-induced decomposition product of hexoses, 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...

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Published in:Journal of Toxicology and Environmental Health, Part A Part A, 1999-06, Vol.57 (3), p.199-210
Main Authors: GODFREY, V. B, CHEN, L.-J, GRIFFIN, R. J, LEBETKIN, E. H, BURKA, L. T
Format: Article
Language:English
Subjects:
5-(Hydroxymethyl)-2-furaldehyde
Animals
Biological and medical sciences
Carcinogens - metabolism
Carcinogens - pharmacokinetics
Food Contamination
Food toxicology
Furaldehyde - analogs & derivatives
Furaldehyde - metabolism
Furaldehyde - pharmacokinetics
hexose
Hot Temperature
Male
Medical sciences
Mice
Rats
Rats, Inbred F344
Tissue Distribution
Toxicology
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Summary:(5-Hydroxymethyl)furfural (HMF), a heat-induced decomposition product of hexoses, 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 toxicology studies, the disposition of [14C]-HMF has been investigated in male F344 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. Excretion 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 radioactivity were greater than 1 for liver and kidney. Three metabolites were identified 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 to be formed from sulfate conjugates. There were relatively low levels of nonextractable radioactivity in liver, kidney, and intestines, indicating that some reactive intermediate(s) may be formed.
ISSN:1528-7394
0098-4108
1087-2620
DOI:10.1080/009841099157764