IRSST - Institut de recherche Robert-Sauvé en santé et en sécurité du travail

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

Summary

Pyrethroid 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 pyrethroid’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 respiratory, dermal and inadvertent 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-cyhalothrinbased formulation) doses of lambda-cyhalothrin, in order to analyze 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 rate 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 parent product and the resulting metabolites are retained in the skin. The modelling did
show, however, that the skin penetration of the molecule was limited, so that a worker’s exposure
doses by that route must be very high to make a significant contribution to the total amounts
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 pyrethroids already
studied: permethrin and cypermethrin. The different metabolites of those pyrethroids in accessible
biological fluids like urine can therefore be measured to assess overall exposure to pyrethroids.
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
pyrethroids, and to reconstruct the doses absorbed under different exposure scenarios.
Furthermore, comparing a farmworker’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 pyrethroids 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.