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 metabolized to the NIH-shifted products 2-hydroxy-1,4,7,8-tetrachlorodibenzo-p-dioxin and 3-hydroxy-1,2,7,8-tetrachlorodibenzo-p-dioxin. The chlorine substitution patterns were determined by comparison with 1H NMR spectra of six synthesized isomers in CDCl3, CD3OD, and acetone-d6. Glucuronide and glucuronide-sulfate conjugates of the monohydroxy dioxins were identified in the bile by FAB-MS. The dominance of the NIH-shift products in the metabolism of tetrachlorodibenzo-p-dioxins indicates that the same isomers may be produced from differently substituted chlorinated dioxins.