Toxic action of benfuracarb via oxidative bioactivation process by cytochrome $P_{450}$

Procarbamate계 살충제 benfuracarb의 산화적 활성화 과정을 통한 독성발현

  • Yu, Yong-Man (Central Institute, Kyung nong Co.) ;
  • Kim, Eun-H. (Agricultural Technology and Extension Center) ;
  • Kim, Song-Mum (Division of Biological Environment, Kangwon National University) ;
  • Hur, Jang-Hyun (Division of Biological Environment, Kangwon National University)
  • 유용만 ((주) 경농 중앙연구소) ;
  • 김은향 (강원도 춘천시 농업기술센터) ;
  • 김성문 (강원대학교 생물환경학부) ;
  • 허장현 (강원대학교 생물환경학부)
  • Published : 2003.03.27

Abstract

This study was conducted to understand the role of oxidative enzyme cytochrome $P_{450}$ in the bioactivation of benfuracarb and to know metabolites of benfuracarb by cytochrome $P_{450}$. The bimolecular imhibition rate constant $(k_i)$ of benfuracarb on acetylcholinesterase (AChE) was as low as $1.1{\times}10^3\;M^{-1}\;min^{-1}$, suggesting that benfuracarb should be activated for its toxic action. The potency of benfuracarb on AChE in the oxidase system (cytochrome $P_{450}$ + NADPH) in vitro was 10-fold higher than that of control (cytochrome $P_{450}$). Such a similar result was also found in the oxidase + PBO system. In vivo the $I_{50}$ of benfuracarb was 22.7mg $kg^{-1}$, but pie-treatment of piperonyl butoxide (PBO) reduced the $I_{50}$ by >100mg $kg^{-1}$. This result suggests that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Using microsomal oxidase system, metabolites of benfuracarb were elucidated. Fifty-eight percent of benfuracarb was converted to carbofuran, a major toxic metabolite, in the oxidase system, while only less than two percent of benfuracarb was converted to carbofuran in the oxidase + PBO system. These results also suggest that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Overall results indicate that cytochrome $P_{450}$ could be involved in the bioactivation of benfuracarb to carbofuran.

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