Feasibility of Biomonitoring of Exposure to Permethrin Through Analysis of Long-Lived (Metabolite) Adducts to Proteins
Annual rept. 1 Sep 2005-31 Aug 2006
TNO DEFENSE SECURITY AND SAFETY RIJSWIJK (NETHERLANDS)
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Biomonitoring of exposure to the insecticide permethrin is usually performed by analysis of its urinary metabolite 3-phenoxybenzoic acid 3- PBA. However, chronic low-level exposures and cumulative exposures cannot be assessed by analyzing urinary biomarkers. 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 cistrans-3-2,2-dichlorovinyl-2,2-dimethylcyclopropane-1-carboxylic acid cistrans-Cl2CA will form persistent adducts to proteins, in analogy with the glucuronide conjugates of structurally related drugs. In the first year of the project the 3-PBA and Cl2CA glucuronide metabolites of permethrin have been successfully chemically synthesized. Their identities have been assessed by means of 1H- NMR spectroscopy and LC tandem mass spectrometry. The reactivity of these metabolites with various amino acids, peptides and albumin has been studied various distinct adducts could be identified by LC tandem mass spectrometry. It is envisaged that the obtained results will form a firm basis for development of an adduct-based methodology for biomonitoring exposure to permethrin.
- Medicine and Medical Research