Session: Session 4

Characterisation of pesticide metabolites to study their effects on health

Emilien JAMIN^1,2, Romain VUILLAUME^1,2, Carla ORLANDI^1,2, Ndeye KHOYANE DIENG^1,2, Nicolas LOISEAU^1,3, Anne FOUGERAT^1,3, Clemence RIVES^1,3, Laurence GAMET-PAYRASTRE^1,3

¹UMR1331 Toxalim (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France
²MetaboHUB-Metatoul, National Infrastructure of Metabolomics and Fluxomics, Metatoul-AXIOM, Toulouse, France
³Toxicology and Integrative Metabolism, UMR1331 Toxalim (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, Toulouse, France

The exposome concept has led to the toxicological assessment of pollutant mixtures. To assess the metabolic consequences of chronic dietary exposure to a pesticide cocktail, a preclinical study was performed with mice fed a standard or a western diet and exposed to the individual admissible daily intake (ADI) of 4 pesticides in mixture. The impact of exposure to pesticide may depend on the biotransformation of each one that could be altered when pesticides are in combination. Thus, the characterization of residues (active substance and its metabolites) not only would support exposure but also provide a better insight of the observed effects. However, in a context of low-dose exposure and in the absence of commercial standards, detecting, identifying, and quantifying metabolites is challenging.

Urinary samples of mice exposed or not to the ADI of pesticides and fed with different diets were analyzed using reversed-phase LC with HRMS detection (TIMS-ToF, Bruker). A list of suspected compounds, including the studied pesticides, their known metabolites, and putative ones, was screened and identified.

Using MS/MS acquired in PASEF mode, CCS measurements by ion mobility, comparisons with some standards, and the interpretation of fragment ions and CCS aided by in silico tools, we were able to detect pesticide metabolites following low-dose exposure. Furthermore, we differentiated metabolite concentrations between each studied dose and, more importantly, between the different diets. Finally, HRMS results were consistent with the observed biological effects on the liver, indicating that diet could modify the bioavailability of pesticides.

Recent advances in mass spectrometry allow the detection, identification, and quantification of low-concentration biomarkers of exposure, facilitating a better understanding of the effects of xenobiotics within the context of exposome. Following these initial results, this approach is also being applied to other diseases, such as Parkinson.