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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.
Acknowledgment
The authors thank Dr. Larry Sheets (Bayer CropScience, NC, USA) for valuable discussions.
Disclosure statement
Dr. M.R. Creek is a consultant to Valent USA LLC, a member of the Council for the Advancement of Pyrethroid Human Risk Assessment (CAPHRA), LLC. Dr. T.G. Osimitz is a consultant to CAPHRA. All other authors have been involved in studies performed for CAPHRA. The authors alone are responsible for the content and writing of this article.