Perfusate from rat livers perfused with benzene (similar to 0.7-7 x 10
(-4) M) or trans, trans-muconaldehyde (MUC) (10(-4) M) was extracted a
nd analyzed by reverse-phase HPLC. Based on retention time and co-elut
ion experiments, benzene was found to be metabolized to trans,trans-mu
conic acid, a urinary ring-opened metabolite of benzene and a major in
vivo and in vitro metabolite of MUC. These data demonstrate that benz
ene ring-opening occurs in the liver. Following perfusion with MUC (a
microsomal hematotoxic metabolite of benzene), trans,trans-muconic aci
d and three other MUC metabolites were detected in the perfusate extra
ct, suggesting that these metabolites would be present in the circulat
ion following metabolism of MUC.