Metabolism of bifenthrin, β-cyfluthrin, λ-cyhalothrin, cyphenothrin and esfenvalerate by rat and human cytochrome P450 and carboxylesterase enzymes

Laura Hedges, Susan Brown (Lead / Corresponding author), A. Kenneth MacLeod, Marjory Moreau, Miyoung Yoon, Moire R. Creek, Thomas G. Osimitz, Brian G. Lake

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The metabolism of bifenthrin (BIF), β-cyfluthrin (CYFL), λ-cyhalothrin (CYHA), cyphenothrin (CYPH) and esfenvalerate (ESF) was studied in liver microsomes, liver cytosol and plasma from male Sprague-Dawley rats aged 90, 21 and 15 days and from adult humans. Pyrethroid metabolism was also studied with some human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. All five pyrethroids were metabolised by adult (90 day old) rat hepatic microsomal CYP and CES enzymes and by cytosolic CES enzymes. The pyrethroids were also metabolised by human liver microsomes and cytosol. Some species differences were observed. Pyrethroid metabolism by cytosolic CES enzymes contributes to the overall hepatic clearance of these compounds. CYFL, CYHA, CYPH and ESF were metabolised by rat plasma CES enzymes, whereas none of the pyrethroids were metabolised by human plasma. This study demonstrates that the ability of male rats to metabolise these pyrethroids by hepatic CYP and CES enzymes and plasma CES enzymes increases with age. In all instances, apparent intrinsic clearance values were lower in 15 than in 90 day old rats. All pyrethroids were metabolised by some of the human expressed CYP enzymes studied and apart from BIF were also metabolised by CES enzymes.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalXenobiotica
Volume50
Issue number12
Early online date16 Jul 2020
DOIs
Publication statusPublished - 22 Jul 2020

Keywords

  • Bifenthrin
  • carboxylesterase
  • cyphenothrin
  • cytochrome P450
  • esfenvalerate
  • human
  • pyrethroids
  • rat
  • β-cyfluthrin
  • λ-cyhalothrin

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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