Feasibility of Biomonitoring of Exposure to Permethrin Through Analysis of Long-Lived (Metabolite) Adducts to Proteins
Abstract
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 cis/trans-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane-1-carboxylic acid (cis/trans-Cl2CA) will form persistent adducts to proteins, in analogy with the glucuronide conjugates of structurally related drugs. In the second year of the project the adduct formation of the glucuronides of 3-PBA and Cl2CA was studied in plasma. A method was developed for analysis of albumin adducts of the glucuronides, which is based on pronase digestion of albumin followed by LC-tandem MS analysis of the lysine adducts. For 3-PBA glucuronide, it was attempted to quantify adduct formation by using [14C] labelled 3-PBA glucuronides, obtained by combined chemical and enzymatic synthesis. Quantitation was thwarted due to non-covalent association of the glucuronides to the proteins. It is envisaged that the obtained results will form a firm basis for development of an adductbased methodology for biomonitoring exposure to permethrin, and that the results will give valuable toxicological information that can be used for risk assessment for the current large-scale use of permethrin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA475256
Entities
People
- Daan Noort