METABOLISM AND DISPOSITION OF 1,4,7,8-TETRACHLORODIBENZO-P-DIOXIN IN RATS

Metabolism studies of 1,4,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a re latively nontoxic dioxin congener, were undertaken to gain a better un derstanding of mammalian metabolism of dioxins without the problems as sociated with the use of the most toxic congener, 2,3,7,8-TCDD. C-14,1 ,4,7,8-TCDD was dosed to conventional and bile-cannulated rats at a le vel of 8 mg/kg. The C-14 was excreted almost entirely in 72 hours with the major routes of excretion feces and bile. Metabolites were identi fied from the feces, bile, and urine by GC-MS or negative ion FAB MS a nd H-1 NMR. The two major fecal metabolites were hydroxylated tetra- a nd triCDDs. Glucuronide and sulfate conjugates of these hydroxyl metab olites were found in the urine and bile. Minor metabolites included di chlorocatechol, dihydroxylated tetra- and triCDDs, and conjugates of t hese compounds. Published by Elsevier Science Ltd.