<i>In vitro</i> and <i>in vivo</i> Metabolism of Fenvalerate in Pyrethroid Resistant Houseflies

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  • FUNAKI Eisuke
    Laboratory of Pesticide Toxicology. Faculty of Horticulture, Chiba University Agrochemical Research Department, Ube Research Laboratory, UBE Industries, Ltd.
  • DAUTERMAN Walter Curl
    Department of Toxicology, North Carolina State University
  • MOTOYAMA Naoki
    Laboratory of Pesticide Toxicology. Faculty of Horticulture, Chiba University

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  • ピレスロイド抵抗性イエバエにおけるフェンバレレートの <i>in vitro</i> および <i>in vivo</i> 代謝
  • ピレスロイド抵抗性イエバエにおけるフェンバレレートのin vitroおよびin vivo代謝〔英文〕
  • ピレスロイド テイコウセイ イエバエ ニ オケル フェンバレレート ノ in

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Abstract

In vitro and in vivo metabolism of phenoxyphenyl or chlorophenyl ring labeled 14C-fenvalerate was studied in pyrethroid resistant and susceptible strains of the housefly. Microsomes fortified with NADPH catalyzed the ester bond cleavage as well as ring hydroxylation at the 4′ position of the phenoxyphenyl group. Subcellular distribution, cofactor dependence, and inhibition with piperonyl butoxide and CO suggested that these reactions were catalyzed by the cytochrome P450-dependent monooxygenase system. Hydrolysis was responsible for a small portion of the ester bond cleavage. The largest interstrain difference was in the oxidative cleavage of the ester bond, which appeared to be due to a specific cytochrome P450 species present only in the pyrethroid resistant strain. Two organophosphate resistant strains with high oxidase activity did not show a significant difference in this activity compared to 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 R/S ratio of excretion rate constant (hr-1) for water-soluble metabolites was 3.8 and 56, respectively. This confirmed the importance of increased detoxification as an additional resistance mechanism as well as decreased nerve sensitivity as previously reported. Cuticular penetration of fenvalerate was not responsible for resistance in the strain studied.

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