Synthesis, biologic and toxic effects of the major 2,3,7,8-tetrachlorodibenzo-p-dioxin metabolites in the rat

G. Mason, S. Safe

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The two major mammalian metabolites of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), namely 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin and 2-hydroxy-1,3,7,8-tetrachlorodibenzo-p-dioxin, have been synthesized. The compounds were individually administered to immature male Wistar rats and their effects on body weight loss, thymic atrophy, liver and spleen weights and their activities as inducers of hepatic microsomal benzo[a]pyrene hydroxylase, 4-chlorobiphenyl hydroxylase and ethoxyresorufin O-deethylase were determined using dose levels of 100, 1000 and 5000 μg/kg. The 2 metabolites did not affect organ or body weights after 14 days of exposure and only 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin was active as an inducer of the microsomal monooxygenases at dose levels of 1000 and 5000 μg/kg. A comparison of the relative enzyme induction activities of 2,3,7,8-TCDD and 2-hydroxy-3,7,8-trichlorodibenzo-p-dioxin indicates that the former compound was greater than 3 orders of magnitude more active than the metabolite.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalToxicology
Volume41
Issue number2
DOIs
StatePublished - Oct 31 1986

Keywords

  • 2,3,7,8-TCDD metabolites
  • Enzyme induction
  • Toxicity

ASJC Scopus subject areas

  • Toxicology

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