IDENTIFICATION OF TETRACHLORODIBENZOFURAN METABOLITES

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The purpose of this project is to identify the glucuronidase/sulfatase- treated, methylated biliary metabolites in rats orally administered 2,3,7,8-tetrachlorodibenzofuran (TCDF) which is a highly toxic contaminant sometimes found in commercial chlorinated phenols and polycyclic biphenyls. The first step in this project was the mass spectral characterization of synthetic potential metabolites along with determination of the GC retention windows. The GC/MS data for 2-methoxy-3,7,8-trichlorodibenzofuran, 3-methoxy- 2,7,8,-tetrachlorodibenzofuran 1-methoxy-2,3,7,8- tetrachlorodibenzofuran, 3-methoxy-2,4,7,8-tetrachlorodibenzofuran and 4-methoxy-2,3,7,8-tetrachlorodibenzofuran were obtained. These data were used as standards to compare with the isolated biliary metabolites. Two components of methylated rat bile extract were determined to be tetrachlorodibenzofuran metabolites. On the basis of their mass spectra and retention times, we have been able to establish the identities of the major metabolites to be 4-methoxy-2,3,7,8-tetrachlorodibenzofuran and 3- methoxy-2,4,7,8-trichlorodibenzofuran. In addition a small amount of unmetabolized TCDF was identified in bile extract. These results were confirmed by analysis of the biliary metabolites of a second rat. Based on these identifications, it appears that the preferred site of metabolism in TCDF is near the furan oxygen with oxidation of the C-H bond taking precedence over oxidation of the C-Cl bond.