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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
Toxicogenomics
  • 141 Downloads

Abstract

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.

Keywords

Background exposure Mixture Pesticides Pharmacokinetic Rat 

Abbreviations

3-PBA

3-Phenoxybenzoic acid

ADME

Absorption, distribution, metabolism, and excretion

ATSDR

Agency for Toxic Substances and Disease Registry

AUC0−∞

Area under the curve

Cmax

Maximum concentration in plasma

Cl2CA

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

ClCF3CA

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

DEP

Diethyl phosphate

DETP

Diethyl thiophosphate

ED30

Effective dose

EDTA

Ethylenediaminetetraacetic acid

EFSA

European Food Safety Authority

FNR

Luxembourg National Research Fund (Fonds National de la Recherche)

GC

Gas chromatography

GC–MS/MS

Gas chromatography with tandem mass spectrometry

HCH

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

LD50

Lethal dose 50%

MRT

Mean residence time

PAH

Polycyclic aromatic hydrocarbon

PCP

Pentachlorophenol

PK

Pharmacokinetics

p,p′-DDD

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethane

p,p′-DDE

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

p,p′-DDT

1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane

SPME

Solid-phase microextraction

T1/2

Terminal elimination half-life

TCPy

3,5,6-Trichloro-2-pyridinol

Tmax

Time to reach the Cmax

WHO

World Health Organization

Notes

Acknowledgements

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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