Mixture risk assessment of pesticides with acute neurotoxic effects: a novel approach based on urinary exposure biomarkers
Abstract
Pesticides showing neurotoxic effects, including organophosphates, pyrethroids, and N-methyl carbamates, are widely used in agriculture. Human biomonitoring (HBM) integrates exposure from multiple sources and routes by measuring pesticide levels in human biological samples. This study applied a novel MRA methodology using urinary biomarkers, focusing on two cumulative assessment groups (CAGs) of pesticides with acute neurotoxic effects, as previously established by the European Food Safety Authority (EFSA), namely, CAG-NAN on brain and/or erythrocyte acetylcholinesterase inhibition; and CAG-NAM on functional alterations of the motor, sensory and autonomic division. Available urinary pesticide metabolites were assigned to potential parent compounds within these CAGs and were converted to external exposure levels, expressed as estimated daily intakes (EDI), using reverse dosimetry. Toxicological reference points, i.e., no observed adverse effect levels (NOAEL) were obtained from EFSA report. For each parent compound, the ratio of the NOAEL to the EDI was calculated, and these ratios were used to determine the total margin of exposure (MOET). This approach was applied as a proof-of-concept to children and adults from 10 HBM studies across seven European countries. For CAG-NAN, median MOET ranged between 27 and 2485 across datasets with percentage of individuals below a threshold of 100 from 2.8 to 97%. For CAG-NAM median MOET values ranged from 34 to 220 000 and in one scenario the percentage of individuals below the threshold was between 24% for children and up to 93% for adults. Azinphos-ethyl, triazophos, omethoate, and chlorpyrifos were identified as risk drivers. This study highlights the need for improved MRA methodologies based on HBM data, including the development of pesticide-specific exposure biomarkers, and the establishment of human biomonitoring-guidance values (HBM-GVs). Incorporating HBM data strengthens human health MRA by reducing uncertainty surrounding non-dietary exposure and generating valuable evidence to inform future pesticide monitoring and regulatory strategies.
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BibTeX
@article{palmont2026mixture,
title = {{Mixture risk assessment of pesticides with acute neurotoxic effects: a novel approach based on urinary exposure biomarkers}},
author = {Philippe Palmont and Madeline Carsique and Karine Angeli and Hannah Mckeon and Alexandra Mienné and Anastasia Spyropoulou and Adna Alilović and Liesbeth Bruckers and Bianca Cox and Pavel Čupr and Katleen Debrouwere and Deepika Deepika and Clémence Fillol and Eva Govarts and Tomáš Janoš and Marike Kolossa-Gehring and Vikas Kumar and Michelle Laeremans and Lucija Perharič and Anja Remškar and Janja Snoj Tratnik Janja Snoj Tratnik and Libor Šulc and Nina Vogel and Aude Ratier and Angelo Moretto and Antonio Hernández-Jerez and Waldo de Boer and Johannes Kruisselbrink and Jasper Engel and Jacob van Klaveren and Kyriaki Machera and Amélie Crépet},
journal = {Environment International},
year = {2026},
month = sep,
doi = {10.1016/j.envint.2026.110531},
url = {https://u-picardie.hal.science/hal-05758856v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mixture risk assessment of pesticides with acute neurotoxic effects: a novel approach based on urinary exposure biomarkers
AU - Philippe Palmont
AU - Madeline Carsique
AU - Karine Angeli
AU - Hannah Mckeon
AU - Alexandra Mienné
AU - Anastasia Spyropoulou
AU - Adna Alilović
AU - Liesbeth Bruckers
AU - Bianca Cox
AU - Pavel Čupr
AU - Katleen Debrouwere
AU - Deepika Deepika
AU - Clémence Fillol
AU - Eva Govarts
AU - Tomáš Janoš
AU - Marike Kolossa-Gehring
AU - Vikas Kumar
AU - Michelle Laeremans
AU - Lucija Perharič
AU - Anja Remškar
AU - Janja Snoj Tratnik Janja Snoj Tratnik
AU - Libor Šulc
AU - Nina Vogel
AU - Aude Ratier
AU - Angelo Moretto
AU - Antonio Hernández-Jerez
AU - Waldo de Boer
AU - Johannes Kruisselbrink
AU - Jasper Engel
AU - Jacob van Klaveren
AU - Kyriaki Machera
AU - Amélie Crépet
PY - 2026
DA - 2026/09/20
JO - Environment International
DO - 10.1016/j.envint.2026.110531
UR - https://u-picardie.hal.science/hal-05758856v1
AB - Pesticides showing neurotoxic effects, including organophosphates, pyrethroids, and N-methyl carbamates, are widely used in agriculture. Human biomonitoring (HBM) integrates exposure from multiple sources and routes by measuring pesticide levels in human biological samples. This study applied a novel MRA methodology using urinary biomarkers, focusing on two cumulative assessment groups (CAGs) of pesticides with acute neurotoxic effects, as previously established by the European Food Safety Authority (EFSA), namely, CAG-NAN on brain and/or erythrocyte acetylcholinesterase inhibition; and CAG-NAM on functional alterations of the motor, sensory and autonomic division. Available urinary pesticide metabolites were assigned to potential parent compounds within these CAGs and were converted to external exposure levels, expressed as estimated daily intakes (EDI), using reverse dosimetry. Toxicological reference points, i.e., no observed adverse effect levels (NOAEL) were obtained from EFSA report. For each parent compound, the ratio of the NOAEL to the EDI was calculated, and these ratios were used to determine the total margin of exposure (MOET). This approach was applied as a proof-of-concept to children and adults from 10 HBM studies across seven European countries. For CAG-NAN, median MOET ranged between 27 and 2485 across datasets with percentage of individuals below a threshold of 100 from 2.8 to 97%. For CAG-NAM median MOET values ranged from 34 to 220 000 and in one scenario the percentage of individuals below the threshold was between 24% for children and up to 93% for adults. Azinphos-ethyl, triazophos, omethoate, and chlorpyrifos were identified as risk drivers. This study highlights the need for improved MRA methodologies based on HBM data, including the development of pesticide-specific exposure biomarkers, and the establishment of human biomonitoring-guidance values (HBM-GVs). Incorporating HBM data strengthens human health MRA by reducing uncertainty surrounding non-dietary exposure and generating valuable evidence to inform future pesticide monitoring and regulatory strategies.
SN - 0160-4120
ER -