Archives of Toxicology

, Volume 93, Issue 10, pp 2849–2862 | Cite as

Blood pharmacokinetic of 17 common pesticides in mixture following a single oral exposure in rats: implications for human biomonitoring and exposure assessment

  • Caroline Chata
  • Paul Palazzi
  • Nathalie Grova
  • Serge Haan
  • Claude EmondEmail author
  • Michel Vaillant
  • Brice M. R. Appenzeller


Human biomonitoring provides information about chemicals measured in biological matrices, but their interpretation remains uncertain because of pharmacokinetic (PK) interactions. This study examined the PKs in blood from Long–Evans rats after a single oral dose of 0.4 mg/kg bw of each pesticide via a mixture of the 17 pesticides most frequently measured in humans. These pesticides are β-endosulfan; β-hexachlorocyclohexane [β-HCH]; γ-hexachlorocyclohexane [γ-HCH]; carbofuran; chlorpyrifos; cyhalothrin; cypermethrin; diazinon; dieldrin; diflufenican; fipronil; oxadiazon; pentachlorophenol [PCP]; permethrin; 1,1-dichloro-2,2bis(4-chlorophenyl)ethylene [p,p′-DDE]; 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane [p,p′-DDT]; and trifluralin. We collected blood at 10 min to 48-h timepoints in addition to one sample before gavage (for a control). We used GS–MS/MS to measure the pesticide (parents and major metabolites) concentrations in plasma, determined the PK parameters from 20 sampling timepoints, and analyzed the food, litter, and cardboard in the rats’ environment for pesticides. We detected many parents and metabolites pesticides in plasma control (e.g., diethyl phosphate [DEP]; PCP; 3-phenoxybenzoic acid [3-PBA]; 3,5,6-trichloro-2-pyridinol [TCPy], suggesting pre-exposure contamination. The PK values post-exposure showed that the AUC0−∞ and Cmax were highest for TCPy and PCP; β-endosulfan, permethrin, and trifluralin presented the lowest values. Terminal T1/2 and MRT for γ-HCH and β-HCH ranged from 74.5 h to 117.1 h; carbofuran phenol presented the shortest values with 4.3 h and 4.8 h. These results present the first PK values obtained through a realistic pattern applied to a mixture of 17 pesticides to assess exposure. This study also highlights the issues of background exposure and the need to work with a relevant mixture found in human matrices.


Background exposure Mixture Pesticides Pharmacokinetic Rat 



3-Phenoxybenzoic acid


Absorption, distribution, metabolism, and excretion


Agency for Toxic Substances and Disease Registry


Area under the curve


Maximum concentration in plasma


Cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid


3-(2-Chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid


Diethyl phosphate


Diethyl thiophosphate


Effective dose


Ethylenediaminetetraacetic acid


European Food Safety Authority


Luxembourg National Research Fund (Fonds National de la Recherche)


Gas chromatography


Gas chromatography with tandem mass spectrometry


Hexachlorocyclohexane (gamma [γ], beta [β])


Lethal dose 50%


Mean residence time


Polycyclic aromatic hydrocarbon








1,1-Dichloro-2,2bis(4-chlorophenyl) ethylene




Solid-phase microextraction


Terminal elimination half-life




Time to reach the Cmax


World Health Organization



Caroline Chata benefited from a Ph.D. grant from the Luxembourg National Research Fund (Fonds National de la Recherche [FNR]) (AFR 7009593), Luxembourg.

Compliance with ethical standards

Conflict of interest

The authors do not have any conflicts of interest to disclose.

Supplementary material

204_2019_2546_MOESM1_ESM.docx (77 kb)
Supplementary material 1 (DOCX 76 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Human Biomonitoring Research UnitLuxembourg Institute of Health (LIH)Esch-sur-AlzetteLuxembourg
  2. 2.Faculty of Science, Technology and CommunicationUniversity of LuxembourgEsch-sur-AlzetteLuxembourg
  3. 3.Life Sciences Research UnitUniversity of LuxembourgBelvauxLuxembourg
  4. 4.PhysioKinetic Simulations to Human Inc. (PKSH Inc)MascoucheCanada
  5. 5.Competence Center for Methodology and StatisticsLuxembourg Institute of Health (LIH)LuxembourgLuxembourg

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