IDENTIFICATION OF 6-HYDROXY-TRANS,TRANS-2,4-HEXADIENOIC ACID, A NOVELRING-OPENED URINARY METABOLITE OF BENZENE

We studied the in vivo metabolism of benzene in mice to ring-opened co mpounds excreted in urine. Male CD-1 mice were treated-intraperitoneal ly with benzene (110-440 mg/kg), [C-14]benzene (220 mg/kg) or trans,tr ans-muconaldehyde (MUC; 4 mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed b y HPLC with a diode-array detector and by scintillation counting. In a ddition to trans,trans-muconic acid, previously the only known ring-op ened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans, tr ans-2,4-hexadienoic acid, was detected in urine of mice treated with e ither benzene or MUC. We identified the new metabolite based on coelut ion of metabolites and UV spectral comparison with authentic standards in unmethylated and methylated urine extracts. Results presented here are consistent with the intermediacy of MUC in the in vivo metabolism of benzene to ring-opened metabolite.