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Lambda-Cyhalothrin Used as an Insecticide in Agriculture ‒ Study of Biomarker Toxicokinetics to Monitor Worker Exposure

Summary

Pyrethrinoid insecticides are a family of pesticides widely used in Quebec to control insect pests in market garden crops. One such insecticide is lambda-cyhalothrin. Despite its extensive use, there is very little data on this pyrethrinoid’s biological behaviour in the human body. It has therefore become essential to develop tools to accurately assess worker exposure to these pesticides during spraying or work in already treated areas. Biological monitoring, by measuring products (called metabolites) excreted in the urine, is considered to be an appropriate method of assessing the doses actually absorbed of this type of product in the workplace. Measuring these exposure biomarkers in farmers provides an indication of combined inadvertent respiratory, dermal and oral exposure and allows varied exposure conditions to be taken into account. Interpretation of biological monitoring data requires a good knowledge of the fate (toxicokinetic behaviour) of the substance of interest in the human body, so that biomarker levels in workers can be related to doses actually absorbed. That relationship was recently established by this research team for permethrin and cypermethrin.

The overall objective of this research project was to address the lack of knowledge about the toxicokinetics of biomarkers of exposure to lambda-cyhalothrin in humans, and so to enable better interpretation of biomonitoring data for workers exposed to this pesticide and better assessment of the associated risks.

The project was divided into two parts. In the first part, a controlled kinetic study was conducted on volunteers exposed acutely to low oral (oral reference dose) and dermal (lambda-cyhalothrin-based formulation) doses of lambda-cyhalothrin, in order to analyse the time profiles of the exposure biomarkers (CFMP and 3-PBA) in their plasma and urine. In the second part, a toxicokinetic model was developed based on data from study volunteers to simulate the kinetics of biomarkers of exposure to lambda-cyhalothrin for various exposure scenarios and to provide a tool for recreating the doses absorbed by exposed workers.

The kinetic study of the volunteers and the data modelling showed that lambda-cyhalothrin enters the body quickly, but that it is also quickly eliminated following exposure through ingestion or skin contact. Measurement of metabolites in plasma or urine therefore reflects recent exposure. The research also revealed differences in the speed of absorption and elimination of lambda-cyhalothrin depending on whether the exposure is oral or dermal. The differences can be explained by the fact that the skin can cause the biotransformation of lambda-cyhalothrin into its metabolites (CFMP and 3-PBA), which serve as exposure biomarkers. They can also be explained by the fact that the mother product and the resulting metabolites are retained in the skin. The modelling did show, however, that the skin resisted penetration of the molecule, so that a worker’s exposure doses by that route must be very high to make a significant contribution to the total quantities absorbed by the different routes (combination of oral, dermal and respiratory).

The results also showed that the behaviour of lambda-cyhalothrin exposure biomarkers (measured in plasma and urine) is similar to that of the metabolites of other pyrethrinoids already studied: permethrin and cypermethrin. The different metabolites of those pyrethrinoids in accessible biological fluids like urine can therefore be measured to assess overall exposure to pyrethrinoids. The modelling was also essential to proposing a urinary level of metabolites that can serve as a biological reference value that should not be exceeded, to reduce the risks of health effects. Exceeding this threshold would be an indicator that workplace practices and hygiene need to be adjusted to limit the risks of harmful effects.

The new kinetic data obtained through the study, as well as the modelling performed, can be used directly to interpret biological monitoring data on worker exposure to lambda-cyhalothrin or other pyrethrinoids, and to reconstitute the doses absorbed under different exposure scenarios. Furthermore, comparing a farm worker’s urinary biomarker levels with the biological reference value proposed as a benchmark can serve to assess the risks associated with exposure to lambda-cyhalothrin and, more broadly, to pyrethrinoids in general. This study has helped advance current knowledge, which will lead to better assessment of exposure and the risks associated with the use of pesticides in agriculture, from a prevention perspective.