Toxicokinetic Model Describing Bioconcentration and Biotransformation of Diazinon in Daphnia magna

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• 作者：Andreas Kretschmann ; Roman Ashauer ; Thomas G. Preuss ; Piet Spaak ; Beate I. Escher ; Juliane Hollender
• 刊名：Environmental Science & Technology
• 出版年：2011
• 出版时间：June 1, 2011
• 年：2011
• 卷：45
• 期：11
• 页码：4995-5002
• 全文大小：921K
• 年卷期：v.45,no.11(June 1, 2011)
• ISSN：1520-5851

文摘

A toxicokinetic model for Daphnia magna, which simulates the internal concentration of the insecticide diazinon, its detoxification product 2-isopropyl-6-methyl-4-pyrimidinol, and its active metabolite diazoxon, is presented. During in vivo exposure to diazinon with and without inhibition of cytochrome P450 by piperonyl butoxide, the parent compound as well as its metabolites were quantified with high-performance liquid chromatography鈥搕andem mass spectrometry (LC-MS/MS) in extracts of D. magna. Rate constants of all relevant toxicokinetic steps were obtained by modeling the time course of the internal concentrations with a multicomponent first-order kinetics model. When cytochrome P450 was inhibited, the kinetic bioconcentration factor (BCF) of diazinon increased from 17.8 to 51.0 mL路g_ww^鈥?. This clearly indicates that diazinon is biotransformed to a high degree by cytochrome P450 in D. magna. The dominant elimination step of diazinon was shown to be its oxidative dearylation to pyrimidinol (62% of total elimination) with a corresponding rate constant of 0.16 h^鈥?. In contrast, oxidative activation to diazoxon with a rate constant of 0.02 h^鈥? amounted to only 8% of the total elimination. During exposure to diazinon, the active metabolite diazoxon could be detected only in very low concentrations (approximately 0.5% of the parent compound), presumably due to a very fast reaction with the target site acetylcholinesterase. During the exposure experiments (no feeding of daphnids), an exponential decline of the lipid content in D. magna with a first-order rate constant of 0.013 h^鈥? was observed. For short exposure times (鈮?4 h), this had only a minor influence on the determined TK parameters. Such a TK model containing detailed biotransformation processes is an important tool for estimation of the toxic potential of chemicals, particularly, when active metabolites are formed inside an organism.