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Stanley A. Kline, J. Forbes Robertson, V. Lee Grotz, Bernard D. Goldstein, and Gisela Witz²

¹Department of Environmental and Community Medicine, University of Medicine and Dentistry-New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854 USA; ²Environmental and Occupational Health Sciences Institute, Piscataway, NJ 08854 USA

Abstract
We studied the in vivo metabolism of benzene in mice to ring-opened compounds excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene (110-440 mg/kg) , [¹⁴C]benzene (220 mg/kg) or trans,trans-muconaldehyde (MUC ; 4 mg/kg) , a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed by HPLC with a diode-array detector and by scintillation counting. In addition to trans,trans-muconic acid, previously the only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with either benzene or MUC. We identified the new metabolite based on coelution 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 metabolites. Key words: benzene, 6-hydroxy-2, 4-hexadienoic acid, muconaldehyde, muconic acid, ring-opened metabolite, urinary metabolite. Environ Health Perspect 101:000-000 (1993)

Address correspondence to G. Witz, Toxicology Division, Environmental Occupational Health Sciences Institute, PO Box 1179, Piscataway, NJ 08855-1179 USA. This work was supported by grant numbers ES02558 and ES05022 from the National Institute of Environmental Health Sciences.

Received 9 Nov 1992 ; revised 17 May 1993.