The comparative biologic and toxic potencies of polychlorinated biphenyls and polybrominated biphenyls

J. Andres, I. Lambert, L. Robertson, S. Bandiera, T. Sawyer, S. Lovering, S. Safe

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Aroclor 1254 and fireMaster BP-6, two commercial polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) preparations, exhibit comparable biologic and toxic effects. In the present study the commercial PBB was more active than Aroclor 1254 in causing thymic atrophy in male Wistar rats. However, a direct comparison of the relative effects of bromine vs chlorine substituents is not possible with the commercial PBB and PCB mixtures due to their complex congeneric composition. This study reports the synthesis and biologic and toxic effects of a series of laterally substituted 3,3′,4,4′-tetrahalobiphenyls which contain the following variable molecular Cl/Br ratios; Br4, Br3Cl, Br2Cl2 (two isomers), BrCl3, and Cl4. 3,3′,4,4′-Tetrabromobiphenyl and 3,4,4′-tribromo-3′-chlorobiphenyl (150 μmol/kg)-pretreated animals significantly inhibited the growth rate of and caused thymic atrophy in immature male Wistar rats whereas those isostereomers with reduced Br (and increased Cl) content were either less active or inactive. Pretreatment of male Wistar rats with 10 μmol/kg of the 3,3′,4,4′-tetrahalobiphenyls and determination of their effects as inducers of the hepatic microsomal drug-metabolizing enzymes also illustrated the effects of the relative Cl/Br ratios on induction potencies. Both 3,3′,4,4′-tetrabromo- and 3,4,4′-tribromo-3′-chlorobiphenyl maximally induced the cytochrome P-448-dependent monooxygenases, benzo[a]pyrene and 4-chlorobiphenyl hydroxylase; the order of potency of the other isostereomers was 4,4′-dibromo-3,3′-dichloro- {reversed tilde equals} 3,4-dibromo-3′,4′-dichlorobiphenyo >4-bromo-3,3′,4′-trichloro->3,3′,4,4′-tetrachlorobiphenyl. With few exceptions this order of potency was observed for the induction of benzo[a]pyrence hydroxylase and ethoxyresorufin O-deethylase in rat hepatoma cells in culture and for their relative binding affinities to the rat cytosolic receptor protein. The data clearly demonstrate that the biologic activities of this group of isosteric halogenated biphenyls are enhanced with increasing bromine substitution and also support the hypothesis that the activities of this class of chemicals are mediated through the receptor.

Original languageEnglish (US)
Pages (from-to)204-215
Number of pages12
JournalToxicology and Applied Pharmacology
Volume70
Issue number2
DOIs
StatePublished - Sep 15 1983

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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