Polychlorinated dibenzofurans; quantitative structure activity relationships

S. Safe, T. Sawyer, G. Mason, S. Bandiera, B. Keys, M. Romkes, J. Piskorska-Pliszczynska, B. Zmudzka, L. Safe

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Polychlorinated dibenzofurans (PCDFs) are highly toxic industrial and combustion by-products which have been identified in diverse environmental matrices and have been implicated as etiologic agents in Yusho poisioning. The development of new synthetic routes in our laboratory has resulted in the unambiguous synthesis of over 50 purified PCDF congeners from their corresponding hydroxylated polychlorobiphenyl precursors. The effects of structure on the activity of PCDFs as inducers of aryl hydrocarbon hydroxylse (AHH) and as ligands for the Ah cytosolic receptor protein were determined. It was apparent that for both bioassays the most active compounds contained 4 lateral (2,3,7 and 8) chlorine atoms and that the degree of lateral substitution was a major structural determinant for activity. The receptor binding and AHH induction potencies (EC50) for the most active PCDF, 2,3,4,7,8-pentachlorodibenzofuran, were 1.5 × 10-8 M and 2.56 × 10-10 M respectively and these values were similar to the induction and receptor binding activities of 2,3,7,8-TCDD (1.0 × 10-8 M and 7.20 × 10-11 M). The in vitro structure-activity relationships (SARs) also indicated that substitution of C1 at the 4 and 6 positions in dibenzofuran gave PCDFs which were significantly more active than their corresponding isomers substituted at C-1 and C-9. The dose-response in vivo toxicities of several PCDFs were also determined in the rat using weight loss and thymic atrophy as toxic end-points. The in vivo quantitative structure-activity relationships for the PCDFs complemented the in vitro studies and confirmed that the more toxic PCDFs were substituted not only in the lateral positions but also at C-6 and C-4 of the dibenzofuran ring system.

Original languageEnglish (US)
Pages (from-to)675-683
Number of pages9
JournalChemosphere
Volume14
Issue number6-7
DOIs
StatePublished - 1985

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Chemistry(all)
  • Pollution
  • Health, Toxicology and Mutagenesis

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