The hepatocarcinogen and toxicant furan requires metabolic activation to elicit its toxic effects. Theavailable experimental evidence indicates that the overall metabolism of furan is initiated via cytochromeP450 catalyzed oxidation to
cis-2-butene-1,4-dial. This
,
-unsaturated dialdehyde reacts in vitro withprotein and DNA nucleophiles. To determine if this compound is an in vivo intermediate in the metabolismof furan, rats were treated with either [
12C
4]furan or [
13C
4]furan, and urine was collected for 24 h. CapillaryLC/MS/MS analysis of the urine indicated that one of the metabolites was a monoglutathione conjugateof
cis-2-butene-1,4-dial. These results indicate that glutathione conjugation of the reactive metabolite offuran occurs in vivo. This metabolite may serve as a useful marker for furan exposure and metabolismin risk assessment studies.