La Lambda-cyhalothrine Comme Insecticide privilégié en Milieu Agricole: étude de la toxicocinétique de Biomarqueurs Pour le Suivi de l'Exposition Des Travailleurs

Lambda-cyhalothrin is a synthetic pyrethroid pesticide widely used in Quebec to fight against pests in vegetable crops. In recent years, this pyrethroid has become one of the most used insecticides in these crops. However, there is a paucity of data on the biological behavior of this molecule in humans. Given the extensive use of this pyrethroid, it becomes essential to develop tools to properly assess exposure among workers largely in contact with pesticides during spraying or work in treated areas. Biological monitoring, which consists of measuring urinary metabolites is considered a preferred approach to evaluate absorbed doses of this type of product in the workplace, given the potentially combined exposure through the respiratory, dermal and oral routes. However, interpretation of biological monitoring data requires a good knowledge of the kinetic behavior of the substance of interest in the human body, to link biomarker levels among workers to actual absorbed doses. The overall objective of this project is to address the lack of knowledge on the toxicokinetics of biomarkers of exposure to lambda-cyhalothrin in humans for a better interpretation of routine biomonitoring data and hence health risks in exposed workers. First, a controlled kinetic study will be conducted in volunteers exposed acutely to a low oral dose of lambda-cyhalothrin (oral reference dose) followed by a cutaneous dose (of lambda-cyhalothrin formulation used by sprayers). The protocol will be similar to a previous one used by our team for toxicokinetic assessment of other pesticides. Secondly, a toxicokinetic model will be developed to simulate the kinetics of biomarkers of exposure to lambda-cyhalothrin, using data from the controlled kinetic study and based on a previous toxicokinetic model for related pyrethroids.

More specifically, volunteers will be exposed orally to 0.025 mg/kg body weight of lambda-cyhalothrin (single oral dosing). According to recent health risk assessment by the US Environmental Protection Agency (US EPA), volunteers should not incur any adverse effects relating to such dosing. Three weeks following oral dosing (to allow complete elimination of the compound from the body), the same volunteers will be exposed dermally to a lambda-cyhalothrin-based formulation used on crops. The formulation will be applied on a 40cm2 surface of the forearm at a concentration corresponding to the one used in the workplace (Matador 120EC). The treated area will not be washed for a period of 6 h. This type of application will be similar to that of exposed workers. Urinary and blood measurements of specific biomarkers of exposure to these insecticides will be performed. These biomarkers of exposure are already known from other studies and have been shown to be good bioindicators of exposure to pyrethroids. The kinetic profile will serve to link absorbed doses to blood and urinary concentrations of metabolites through time. Personal information on health status, diet and lifestyle will be documented. A total of 7 volunteers will spend a full day at the University during which they will be exposed to a low dose of pesticide. Blood and urinary samples will be collected. Four short visits of one hour will be needed for blood collections. Every urine void for a period of 84 hours will be collected in a different bottle. This whole process will be repeated twice to test two routes of exposure to this insecticide, oral (swallowed) and dermal (applied to the forearm).

The study in volunteers exposed to lambda-cyhalothrin in controlled conditions will allow acquiring new urinary and blood metabolite profiles to better understand their kinetic behavior and essential biological determinants of the observed profiles. These data can then be used in a toxicokinetic model to predict the main routes of exposure and associated absorbed doses in workers exposed to formulations containing lambda-cyhalothrin.