IDENTIFICATION OF NIH-SHIFTED METABOLITES OF 1,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN THE RAT BY NMR COMPARISON WITH SYNTHESIZED ISOMERS

In the rat, 1,3,7,8-tetrachlorodibenzo-p-dioxin was oxidatively metabo lized to the NM-shifted products 2-hydroxy-1,4,7,8-tetrachlorodibenzo- p-dioxin and 3-hydroxy-1,2,7,8-tetrachlorodibenzo-p-dioxin. The chlori ne substitution patterns were determined by comparison with H-1 NMR sp ectra of six synthesized isomers in CDCl3, CD3OD, and acetone-d(6). Gl ucuronide and glucuronide-sulfate conjugates of the monohydroxy dioxin s were identified in the bile by FAB-MS. The dominance of the NM-shift products in the metabolism of tetrachlorodibenzo-p-dioxins indicates that the same isomers may be produced from differently substituted chl orinated dioxins. Published by Elsevier Science Ltd.