Comparative metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices

Robyn L. Fisher, Steven J. Hasal, I. Glenn Sipes, A. Jay Gandolfi, Klaus Brendel

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

1 Precision-cut liver slices, prepared from Sprague- Dawley and Fischer-344 rats and donated human liver tis sue, were used to identify differences in 1,2-dichloroben zene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB) and 1,4- dichlorobenzene (1,4-DCB) metabolism and how it may relate to toxicity. 2 Rat and human liver slices were incubated with 1 mM of either dichlorobenzene to determine metabolism and toxi city, at 2 and 6 h of organ culture. 3 The human liver slices metabolised the dichloroben zenes to a greater extent than those from either of the rat strains. Liver slices from the Fischer-344 strain had a higher metabolic rate than the slices from the Sprague- Dawley rat strain. 4 The metabolic rate of dichlorobenzene isomers did not consistently correlate with its toxicity. For example, human slices did not exhibit any hepatotoxicity, even though they metabolised these compounds to a greater extent than either rat strain. 5 Cross species covalent binding did not correlate with toxicity endpoints measured in this study. 6 The phase two metabolite profiles for each of the iso mers in human and rat slices were similar in that the glu tathione-cysteine conjugate was the major metabolite. 7 The use of an in vitro system which utilises human liver slices might provide an important bridge between animal derived data and the human situation.

Original languageEnglish (US)
Pages (from-to)414-421
Number of pages8
JournalHuman & Experimental Toxicology
Volume14
Issue number5
DOIs
StatePublished - May 1995

Keywords

  • dichlorobenzenes
  • hepatotoxicity
  • human liver slices
  • metabolism
  • rat liver slices

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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