Toxicokinetic Modeling of Biomarkers of Exposure to Lambda-Cyhalothrin for Predicting Exposure and Determining Biological Reference Values

摘要

A multi-compartment toxicokinetic model was developed to predict the time courses of the widely used pyrethroid lambda-cyhalothrin and its metabolites (CFMP and 3-PBA) in the human body and in accessible biological matrices following different exposure scenarios. Model parameters were determined using blood and urinary time course data of metabolites (CFMP and 3-PBA) in volunteers exposed to lambda-cyhalothrin by the oral and dermal routes. The modeling confirmed that the kinetics of biomarkers of exposure to lambda-cyhalothrin was similar to that of permethrin and cypermethrin metabolites. For the oral route, the model conceptual and functional representation is similar to the one previously developed by our team for permethrin and cypermethrin. However, representation of the dermal route has been improved to account for the metabolism of the pesticide in the skin by carboxylesterases. The model can be used to simulate single, multiple or continuous exposure scenarios, and multiple and/or simultaneous exposure pathways (oral, dermal or inhalation). Modeling was further used to derive biological reference values (BRVs) for the specific metabolite of lambda-cyhalothrin (CFMP) not to exceed to prevent health effects based on simulations of an exposure to the lambda-cyhalothrin reference dose values (RfD) established by the U.S. Environmental Protection Agency (0.0025 mg/kg bw/day for acute exposure and 0.001 mg/kg bw/day for chronic exposure). The BRV derived for an acute exposure scenario was 199 pmol/kg bw/day or 0.2 nmol/kg bw of CFMP in a 24 h urine collection, which corresponds to 0.9 pmol/mol creatinine. The BRV simulated for a chronic exposure scenario was 0.08 nmol/kg bw/day or 0.3 pmol/mol creatinine.