Print Email Facebook Twitter Protein adduct formation by glucuronide metabolites of permethrin Title Protein adduct formation by glucuronide metabolites of permethrin Author Noort, D. van Zuylen, A. Fidder, A. van Ommen, B. Hulst, A.G. TNO Defensie en Veiligheid Publication year 2008 Abstract Biomonitoring of exposure to the insecticide permethrin is usually performed by analysis of its urinary metabolites 3-phenoxybenzoic acid (3-PBA) or cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Cl2CA). We are engaged in the development of a methodology to assess the cumulative internal dose of exposure to permethrin, which is based on the assumption that (reactive) glucuronide conjugates of the major permethrin metabolites 3-PBA and Cl2CA will form persistent (weeks to months) adducts to proteins, in analogy with the glucuronide conjugates of structurally related drugs. The 3-PBA and Cl2CA β-glucuronide metabolites of permethrin have been successfully chemically and enzymatically synthesized. Their identities have been assessed by means of 1H NMR spectroscopy and liquid chromatography-tandem mass spectrometry. The reactivity of these metabolites with various amino acids, peptides, and albumin in human plasma has been studied. Several distinct adducts could be identified by liquid chromatography-tandem mass spectrometry. After pronase digestion of albumin isolated from exposed human plasma, various lysine derivatives resulted with favorable mass spectrometric and chromatographic properties. Covalent binding was quantified by using [14C]-3-PBA glucuronide; >1.5% of total radioactivity was bound to proteins. It is envisaged that the obtained results can form a firm basis for the development of a protein adduct-based methodology for biomonitoring exposure to permethrin. In view of the widespread use of permethrin, the toxicological relevance of protein binding by its metabolites will be addressed in more detail in future work. © 2008 American Chemical Society. Subject Nutrition3 (2,2 dichlorovinyl) 2,2 dimethylcyclopropane 1 carboxylic acid3 phenoxybenzoic acidAlbuminAmino acidBenzoic acid derivativeCarboxylic acid derivativeGlucuronideLysine derivativePeptidePermethrinPronaseArticleBiological monitoringChemical structureComplex formationCovalent bondCrug conjugationEnzyme synthesisLiquid chromatographyMetaboliteProtein adductProtein bindingProton nuclear magnetic resonanceRadioactivitySynthesisTandem mass spectrometryChromatography, High Pressure LiquidEnvironmental MonitoringGlucuronidesHumansInsecticidesLysineMagnetic Resonance SpectroscopyMicrosomes, LiverPermethrinPesticide ResiduesProtein BindingSerum AlbuminSpectrometry, Mass, Electrospray IonizationTandem Mass SpectrometryChemicals3 phenoxybenzoic acid, 3739-38-6Amino acid, 65072-01-7Permethrin, 51877-74-8, 52645-53-1Pronase, 9036-06-0GlucuronidesInsecticidesLysine, 56-87-1Permethrin, 52645-53-1Pesticide residuesSerum albumin To reference this document use: http://resolver.tudelft.nl/uuid:f91594a7-90b9-4924-ab3a-d19f44103188 DOI https://doi.org/10.1021/tx8000362 TNO identifier 240902 ISSN 0893-228X Source Chemical Research in Toxicology, 21 (7), 1396-1406 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.