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OXIDATIVE AND HYDROLYTIC METABOLISM OF TYPE I PYRETHROIDS IN RAT HEPATIC MICROSOMES
Citation:
SCOLLON, E., J. M. STARR, M. F. HUGHES, AND M. J. DEVITO. OXIDATIVE AND HYDROLYTIC METABOLISM OF TYPE I PYRETHROIDS IN RAT HEPATIC MICROSOMES. Presented at Society of Toxicology Annual Meeting, San Diego, CA, March 05 - 09, 2006.
Description:
Pyrethroids are a class of neurotoxic insecticides used in a variety of agricultural and household activities. Increased potential for human exposure to pyrethroids has prompted pharmacokinetic research. To that end, our lab has determined the in vitro clearance of the Type I pyrethroids permethrin, bifenthrin, and resmethrin in male rat hepatic microsomes. The aim of this study was to determine the fraction of clearance due to NADPH-dependent oxidative metabolism and NADPH-independent hydrolytic metabolism. 0.5 ?M solutions of cis-permethrin, trans-permethrin, bifenthrin and resmethrin were incubated in hepatic microsomes in the presence or absence of NADPH. Metabolism was measured using a parent depletion approach. Parent compound concentrations were determined by LC/MS. Clearance rates for individual chemicals incubated with NADPH (1mg/ml) were 4.93E-02, 2.00E-02, 1.25E-02, and 3.8E-02 L/hr per mg protein for cis-permethrin, trans-permethrin, bifenthrin, and resmethrin. In the absence of NADPH, trans-permethrin (1.22E-02 L/hr) and resmethrin (9.67E-03 L/hr) were metabolized at reduced but significant rates while cis-permethrin and bifenthrin were not appreciably cleared. The clearance rates for the cis- and trans- isomers in a commercial mixture of permethrin (21:79 cis:trans) were similar to the rates obtained for the pure isomers. Clearance for cis-, trans- and total permethrin were 5.99E-02, 3.19E-02 and 4.37E-02 L/hr per mg protein when incubated with NADPH. In the absence of NADPH, cis- did not degrade significantly but trans- and total permethrin were cleared at 1.9E-02 and 1.62E-02 L/hr per mg protein. It appears that at concentrations below Km, chemical interactions are not significant between cis- and trans-permethrin. (This abstract does not represent US EPA policy.)