Comparative metabolism and disposition of furfural and furfuryl alcohol in rats.
The comparative metabolism and disposition of furfural (FAL) and furfuryl alcohol (FOL) were investigated following oral administration of approximately 0.001, 0.01, and 0.1 of the LD50, corresponding to approximately 0.127, 1.15, and 12.5 mg/kg for FAL and 0.275, 2.75, and 27.5 mg/kg for FOL. At all doses studied, at least 86-89% of the dose of FAL or FOL was absorbed from the gastrointestinal tract. FAL and FOL were extensively metabolized prior to excretion. The major route of excretion was in urine, where 83-88% of the dose was excreted, whereas 2-4% was excreted in the feces. Approximately 7% of the dose from rats treated with FAL at 12.5 mg/kg was exhaled as 14CO2. At 72 hr following administration, the pattern of tissue distribution of radioactivity was similar for both FAL and FOL. Liver and kidney contained the highest, and brain the lowest concentrations of radioactivity. Generally, the concentrations of radioactivity in tissues were proportional to the dose. Almost all of the urinary radioactivity was tentatively identified. No FAL or FOL was detected in urine. Furoylglycine was the major urinary metabolite (73-80% of dose), and furoic acid (1-6%) and furanacrylic acid (3-8%) were the minor metabolites following treatment with either FAL or FOL. Therefore, the initial step in the metabolism of FAL and FOL involves the oxidation to furoic acid, which is excreted unchanged and decarboxylated to form 14CO2, conjugated with glycine, or condensed with acetic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism and Pharmacokinetics Unit, Arthur D. Little, Inc.
A A
AA
Nomeir
D M
DM
Silveira
M F
MF
McComish
M
M
Chadwick
D000818:Animals; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005662:Furaldehyde / Q000493:pharmacokinetics* / Q000652:urine; D005663:Furans / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D005663:Furans; C012986:furfuryl alcohol; D005662:Furaldehyde