Abstract

The French Nutrition and Health Survey (ENNS) reported higher biomarker levels of exposure to pyrethroids than those observed in North American and German biomonitoring studies. The authors therefore investigated aggregate exposure to permethrin as an initial case study because this compound is one of the most widely-used pyrethroid insecticides. We assessed several contamination sources—such as indoor and outdoor air, settled dust and diet—and several pathways, including oral, inhalation and dermal routes. We used permethrin exposure level estimations (computed from ENNS data) and a PBPK model calibrated with human kinetic data (from 6 individuals) to simulate an internal dose of cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- or trans-DCCA) in a population of 219 individuals. The urinary concentrations of cis- and trans -DCCA predicted by the PBPK model according to three permethrin exposure scenarios (“lower”, “intermediate”, and “upper”), were compared to the urinary levels measured in the ENNS study. The ENNS levels were between the levels simulated according to permethrin exposure scenarios “lower” and “intermediate”. The “upper” scenario led to an overestimation of the predicted urinary concentration levels of cis - and trans -DCCA compared to those measured in the ENNS study. The most realistic scenario was the “lower” one (permethrin concentration of left-censored data considered as 0). Using PBPK modeling, we estimated the contribution of each pathway and source to the internal dose. The main route of permethrin exposure was oral (98%), diet being the major source (87%) followed by dust (11%) then the dermal route (1.5%) and finally inhalation (0.5%).

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