Received for publication February 28, 2007.
Revised June 12, 2007.
Accepted for publication June 13, 2007.

Identification of rat and human cytochrome P450 isoforms and a rat serum esterase that metabolize the pyrethroid insecticides deltamethrin and esfenvalerate

Abstract

The metabolism of deltamethrin and esfenvalerate by rat and human liver microsomes differ with respect to the biotransformation pathway (oxidation versus hydrolysis) responsible for their clearance. This study aims to further explore the species differences in the metabolism of these chemicals. Using a parent depletion approach, rat and human CYPs were screened for their ability to eliminate deltamethrin or esfenvalerate during in vitro incubations. Rat CYP isoforms 1A1, 2C6, 2C11, 3A2 and human CYP isoforms 2C8, 2C19,and 3A5 were capable of metabolizing either pyrethroid. Human CYP2C9 metabolized esfenvalerate but not deltamethrin. Rat and human CYPs that metabolize esfenvalerate and deltamethrin do so with similar kinetics. In addition to the liver, a potential site of metabolic elimination of pyrethroids is the blood via serum carboxylesterase (CEs) hydrolysis. The serum of rats, but not humans, contains significant quantities of CEs. Deltamethrin and esfenvalerate were metabolized effectively by rat serum and a purified rat serum CE. In contrast, neither pyrethroid was metabolized by human serum or purified human serum esterases (acetylcholinesterase and butyrylcholinesterase). These studies suggest that the difference in rates of oxidative metabolism of pyrethroids by rat and human hepatic microsomes are dependent on the expression levels of individual CYP isoforms rather than their specific activity. Furthermore, these studies show that the metabolic elimination of deltamethrin and esfenvalerate in blood may be important to their disposition in the rat but not in the human.

Key words: carboxylesterases, cytochrome P450, cytochrome P450 isoforms, environmental toxicology, human CYP enzymes, insecticides

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