Show simple item record

dc.contributor.authorTian, Yuan
dc.date.accessioned2016-03-31T14:21:39Z
dc.date.available2016-03-31T14:21:39Z
dc.date.issued2011
dc.identifier.isbn9781124935584
dc.identifier.other900443162
dc.identifier.urihttp://hdl.handle.net/10477/47185
dc.description.abstractOrganophosphorous pesticides (OPs) remain a potential concern to human health because of their continuing worldwide use. Diazinon is one of the OPs commonly used in agriculture, but since 2004 it is no longer approved for indoor residential use in the U.S. Like other OPs, diazinon is metabolized by cytochromes P450 (CYPs) either by a desulfuration reaction that results in an active oxon moiety, diazinon oxon, which is a potent acetylcholinesterase (AChE) inhibitor or by a dearylation reaction that result in a detoxification product, pyrimidinol (IMP), which is specific to diazinon. The balance between the rates of desulfuration (activation) and dearylation (detoxification) should, in-part, determine the risk to humans for diazinon. This study investigated the rate of desulfation and dearylation of diazinon. Pooled human liver microsomes were used to assess the metabolism of diazinon by measuring the rate of formation of its metabolites diazinon oxon and IMP. Apparent K m and V max values for the formation of the active oxon moiety were 29.9uM and 729 pmol/min/mg protein while the kinetc parameters for formation of the detoxified metabolite IMP were 31.4uM and 1184 pmol/min/mg protein. In addition, recombinant human CYPs were used to quantify CYP-specific kinetic values for diazinon. CYP2C19, 1A1, and 2B6 were the primary enzymes involved in bioactivation while CYP2C19 was the major enzyme involved in diazinon detoxification. CYP-specific kinetic values for diazinon metabolism can be utilized in refining a human physiologically based pharmacokinetic and phamacodynamic (PBPK/PD) model which can better assess human exposure and health risks for diazinon.
dc.languageEnglish
dc.sourceDissertations & Theses @ SUNY Buffalo,ProQuest Dissertations & Theses Global
dc.subjectHealth and environmental sciences
dc.subjectDiazinon
dc.subjectHuman cytochrome p450
dc.subjectPbpk/pd model
dc.titleHuman Cytochrome P450 Specific Metabolism of Diazinon
dc.typeDissertation/Thesis


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record