IN-VITRO AND IN-VIVO METABOLISM OF FENVALERATE IN PYRETHROID-RESISTANT HOUSEFLIES

In vitro and in vivo metabolism of phenoxyphenyl or chlorophenyl ring labeled C-14-fenvalerate was studied in pyrethroid resistant and susce ptible strains of the housefly. Microsomes fortified with NADPH cataly zed the ester bond cleavage as well as ring hydroxylation at the 4' po sition of the phenoxyphenyl group. Subcellular distribution, cofactor dependence, and inhibition with piperonyl butoxide and CO suggested th at these reactions were catalyzed by the cytochrome P450-dependent mon ooxygenase system. Hydrolysis was responsible for a small portion of t he ester bond cleavage. The largest interstrain difference was in the oxidative cleavage of the ester bond, which appeared to be due to a sp ecific cytochrome P450 species present only in the pyrethroid resistan t strain. Two organophosphate resistant strains with high oxidase acti vity did not show a significant difference in this activity compared t o the susceptible strain. When equidoses of fenvalerate resulting in a LD10 and a LD90 were applied to the resistant and susceptible strains in vivo, the RIS ratio of excretion rate constant (hr-1) for water-so luble metabolites was 3.8 and 56, respectively. This confirmed the imp ortance of increased detoxification as an additional resistance mechan ism as well as decreased nerve sensitivity as previously reported. Cut icular penetration of fenvalerate was not responsible for resistance i n the strain studied.