Metabolic activation of phosphorothioate pesticides: Role of the liver

L. G. Sultatos, L. D. Minor, S. D. Murphy

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Mouse liver perfusion studies in situ revealed that the cholinesterase inhibitor chlorpyrifos oxon produced by the liver from the phosphorothioate pesticide chlorpyrifos was quickly detoxified within the liver, thereby preventing its exit from the liver in the effluent. In contrast, when the pesticide parathion was perfused as a substrate a substantial amount of the toxic metabolite paraoxon was found in exiting perfusate. Pesticide concentrations (5-15 μM) used in the perfusion studies in situ were similar to their hepatic portal blood concentrations in vivo (2.32-12.95 μM) after i.p. administration of lethal or near lethal doses. Moreover, the half-life for elimination of paraoxon by mouse blood in vitro was 8.6 min, a rate sufficiently low to allow passage of paraoxon to extrahepatic target tissues from liver in vivo. These results suggest that in the mouse, the acute toxicity of chlorpyrifos is mediated by extrahepatic production of oxon, whereas that of parathion is likely mediated by both hepatic and extrahepatic activation.

Original languageAmerican English
Pages (from-to)624-628
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


Dive into the research topics of 'Metabolic activation of phosphorothioate pesticides: Role of the liver'. Together they form a unique fingerprint.

Cite this