Abstract
We developed a method to quantify cis-permethrin and trans-permethrin and their metabolites in several biological matrices in pregnant rats and foetuses using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The objective was to quantify cis-permethrin and trans-permethrin in faeces, kidney, mammary gland, fat and placenta in mothers and in both maternal and foetal blood, brain and liver. The metabolites cis-3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were measured in blood, liver and urine. Sample preparation was performed by liquid-liquid extraction. A purification step was not carried out except for the more complex biological samples (fat, mammary glands and faeces). Validation parameters including specificity, linearity, matrix effect, limits of quantification (LOQs), accuracy and precision were evaluated. The recoveries of target compounds ranged from 47 to 136%. LOQs were in the range 4 to 80 ng/mL for permethrin isomers and 4 to 800 ng/mL for their respective metabolites. Intra- and inter-batch precision and accuracy in matrix were better than 15%. The validated method was applied in a preliminary toxicokinetic study in pregnant rats with oral dosing of 50 mg/kg permethrin. In pregnant rats, permethrin isomers and their metabolites were quantified in all requested matrices except maternal liver and blood for trans-permethrin and cis-DCCA respectively. In foetuses, cis- and trans-permethrin were also quantified, demonstrating that the method is suitable for the analysis of foetal distribution of permethrin in toxicokinetic studies.
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References
Saillenfait A-M, Ndiaye D, Sabaté J-P. Pyrethroids: exposure and health effects – an update. Int J Hyg Environ Health. 2015;218:281–92. https://doi.org/10.1016/j.ijheh.2015.01.002.
Heudorf U, Angerer J. Metabolites of pyrethroid insecticides in urine specimens: current exposure in an urban population in Germany. Environ Health Perspect. 2001;109:213.
Barr DB, Olsson AO, Wong L-Y, Udunka S, Baker SE, Whitehead RD, et al. Urinary concentrations of metabolites of pyrethroid insecticides in the general U.S. population: National Health and Nutrition Examination Survey 1999–2002. Environ Health Perspect. 2010;118:742–8. https://doi.org/10.1289/ehp.0901275.
Dereumeaux C, Fillol C, Charles M-A, Denys S. The French human biomonitoring program: first lessons from the perinatal component and future needs. Int J Hyg Environ Health. 2017;220:64–70. https://doi.org/10.1016/j.ijheh.2016.11.005.
Soderlund DM. Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances. Arch Toxicol. 2012;86:165–81. https://doi.org/10.1007/s00204-011-0726-x.
Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs. Environ Health Perspect. 2004;113:123–36. https://doi.org/10.1289/ehp.7254.
Horton MK, Rundle A, Camann DE, Boyd Barr D, Rauh VA, Whyatt RM. Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment. PEDIATRICS. 2011;127:e699–706. https://doi.org/10.1542/peds.2010-0133.
Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect. 2014. https://doi.org/10.1289/ehp.1307044.
Fluegge KR, Nishioka M, Wilkins JR III. Effects of simultaneous prenatal exposures to organophosphate and synthetic pyrethroid insecticides on infant neurodevelopment at three months of age. J Environ Toxicol Public Health. 2016;1:60.
Hisada A, Yoshinaga J, Zhang J, Kato T, Shiraishi H, Shimodaira K, et al. Maternal exposure to pyrethroid insecticides during pregnancy and infant development at 18 months of age. Int J Environ Res Public Health. 2017;14:52. https://doi.org/10.3390/ijerph14010052.
Richardson JR, Taylor MM, Shalat SL, Guillot TS, Caudle WM, Hossain MM, et al. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J. 2015;29:1960–72. https://doi.org/10.1096/fj.14-260901.
US EPA. Pesticides industry sales and usage 2008-2012. Market estimates. 2016.
Stout DM II, Bradham KD, Egeghy PP, Jones PA, Croghan CW, Ashley PA, et al. American Healthy Homes Survey: a national study of residential pesticides measured from floor wipes. Environ Sci Technol. 2009;43:4294–300. https://doi.org/10.1021/es8030243.
Starr JM, Scollon EJ, Hughes MF, Ross DG, Graham SE, Crofton KM, et al. Environmentally relevant mixtures in cumulative assessments: an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids. Toxicol Sci. 2012;130:309–18. https://doi.org/10.1093/toxsci/kfs245.
Yan X, Lashley S, Smulian JC, Ananth CV, Barr DB, Ledoux TA, et al. Pesticide concentrations in matrices collected in the perinatal period in a population of pregnant women and newborns in New Jersey, USA. Hum Ecol Risk Assess Int J. 2009;15:948–67. https://doi.org/10.1080/10807030903153089.
Willemin M-E, Desmots S, Le Grand R, Lestremau F, Zeman FA, Leclerc E, et al. PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats. Toxicol Appl Pharmacol. 2016;294:65–77. https://doi.org/10.1016/j.taap.2016.01.011.
Côté J, Bonvalot Y, Carrier G, Lapointe C, Fuhr U, Tomalik-Scharte D, et al. A novel toxicokinetic modeling of cypermethrin and permethrin and their metabolites in humans for dose reconstruction from biomarker data. PLoS One. 2014;9:e88517. https://doi.org/10.1371/journal.pone.0088517.
Tornero-Velez R, Davis J, Scollon EJ, Starr JM, Setzer RW, Goldsmith M-R, et al. A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application. Toxicol Sci. 2012;130:33–47. https://doi.org/10.1093/toxsci/kfs236.
Leng G, Kühn K-H, Idel H. Biological monitoring of pyrethroids in blood and pyrethroid metabolites in urine: applications and limitations. Sci Total Environ. 1997;199:173–81.
Toledo Netto P, Teixeira Júnior OJ, de Camargo JLV, Lúcia Ribeiro M, de Marchi MRR. A rapid, environmentally friendly, and reliable method for pesticide analysis in high-fat samples. Talanta. 2012;101:322–9. https://doi.org/10.1016/j.talanta.2012.09.034.
Du J, Yan H, She D, Liu B, Yang G. Simultaneous determination of cypermethrin and permethrin in pear juice by ultrasound-assisted dispersive liquid-liquid microextraction combined with gas chromatography. Talanta. 2010;82:698–703. https://doi.org/10.1016/j.talanta.2010.05.035.
Lestremau F, Willemin M-E, Chatellier C, Desmots S, Brochot C. Determination of cis-permethrin, trans-permethrin and associated metabolites in rat blood and organs by gas chromatography–ion trap mass spectrometry. Anal Bioanal Chem. 2014;406:3477–87. https://doi.org/10.1007/s00216-014-7774-z.
Hooshfar S, Gullick DR, Linzey MR, Mortuza T, Abdel Rahman MH, Rogers CA, et al. Simultaneous determination of cis-permethrin and trans-permethrin in rat plasma and brain tissue using gas chromatography–negative chemical ionization mass spectrometry. J Chromatogr B. 2017;1060:291–9. https://doi.org/10.1016/j.jchromb.2017.06.019.
Bielawski D, Ostrea E, Posecion N, Corrion M, Seagraves J. Detection of several classes of pesticides and metabolites in meconium by gas chromatography-mass spectrometry. Chromatographia. 2005;62:623–9.
Berkowitz GS, Obel J, Deych E, Lapinski R, Godbold J, Liu Z, et al. Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort. Environ Health Perspect. 2002;111:79–84. https://doi.org/10.1289/ehp.5619.
Starr JM, Graham SE, Ross DG, Tornero-Velez R, Scollon EJ, DeVito MJ, et al. Environmentally relevant mixing ratios in cumulative assessments: a study of the kinetics of pyrethroids and their ester cleavage metabolites in blood and brain; and the effect of a pyrethroid mixture on the motor activity of rats. Toxicology. 2014;320:15–24. https://doi.org/10.1016/j.tox.2014.02.016.
Official Journal of the European Union. Directive 2010/63/EU of the European Parliament and of the Council of the 22 September 2010 on the protection of animals used for scientific purposes. 2010.
The European Agency for the Evaluation of Medical Products. Guideline on bioanalytical method validation. EMEA/CHMP/EWP/192217/2009 Rev1. Corr.2. 2011.
Commission E. Guidance document on analytical quality control and method validation procedures for pesticides residues analysis in food and feed. SANTE/ 11945/2015. Brussels. 2015.
Abu-Qare AW, Abou-Donia MB. Simultaneous determination of chlorpyrifos, permethrin, and their metabolites in rat plasma and urine by high-performance liquid chromatography. J Anal Toxicol. 2001;25:275–9.
Anadon A, Martinez-Larranaga MR, Diaz MJ, Bringas P. Toxicokinetics of permethrin in the rat. Toxicol Appl Pharmacol. 1991;110:1–8.
New L-S, Chan ECY. Evaluation of BEH C18, BEH HILIC, and HSS T3 (C18) column chemistries for the UPLC-MS-MS analysis of glutathione, glutathione disulfide, and ophthalmic acid in mouse liver and human plasma. J Chromatogr Sci. 2008;46:209–14. https://doi.org/10.1093/chromsci/46.3.209.
Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF. In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome P450 isoforms. Drug Metab Dispos. 2009;37:221–8. https://doi.org/10.1124/dmd.108.022343.
Acknowledgements
This work was supported by the French Ministry of Ecology and Sustainable Development (Program 190). We would like to acknowledge Dr. Sophie Desmots for her help with the animal study.
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All experimental procedures were carried out in compliance with the Directive of the European Parliament and the Council (2010/63/UE) concerning the protection of animals used for scientific purpose [27] and approved by an internal ethics committee (C2EA-96).
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Personne, S., Marcelo, P., Pilard, S. et al. Determination of maternal and foetal distribution of cis- and trans-permethrin isomers and their metabolites in pregnant rats by liquid chromatography tandem mass spectrometry (LC-MS/MS). Anal Bioanal Chem 411, 8043–8052 (2019). https://doi.org/10.1007/s00216-019-02157-7
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DOI: https://doi.org/10.1007/s00216-019-02157-7