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

R. I. Fisher, S. J. Hasal, I. G. Sipes, A Jay Gandolfi, K. Brendel

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Abstract

1 - Precision-cut liver slices, prepared from Sprague-Dawley and Fischer-344 rats and donated human liver tissue, were used to identify differences in 1,2-dichlorobenzene (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 toxicity, at 2 and 6 h of organ culture. 3 - The human liver slices metabolised the dichlorobenzenes 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 isomers in human and rat slices were similar in that the glutathione 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 and Experimental Toxicology
Volume14
Issue number5
Publication statusPublished - 1995

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Keywords

  • Dichlorobenzenes
  • Hepatotoxicity
  • Human liver slices
  • Metabolism
  • Rat liver slices

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

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