Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep 23:9:730383.
doi: 10.3389/fped.2021.730383. eCollection 2021.

Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model

Stéphane Personne  1   2 , Céline Brochot  2 , Paulo Marcelo  3 , Aurélie Corona  1 , Sophie Desmots  2 , Franck Robidel  2 , Anthony Lecomte  2 , Véronique Bach  1 , Florence Zeman  2
Affiliations

Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model

Stéphane Personne et al. Front Pediatr. .

Abstract

Biomonitoring studies have highlighted the exposure of pregnant women to pyrethroids based on the measurement of their metabolites in urine. Pyrethroids can cross the placental barrier and be distributed in the fetus as some pyrethroids were also measured in the meconium of newborns. Prenatal exposure to pyrethroids is suspected to alter the neurodevelopment of children, and animal studies have shown that early life exposure to permethrin, one of the most commonly used pyrethroid in household applications, can alter the brain development. This study aimed to characterize the fetal permethrin exposure throughout gestation in rats. We developed a pregnancy physiologically based pharmacokinetic (pPBPK) model that describes the maternal and fetal kinetics of the cis- and trans- isomers of permethrin during the whole gestation period. Pregnant Sprague-Dawley rats were exposed daily to permethrin (50 mg/kg) by oral route from the start of gestation to day 20. Permethrin isomers were quantified in the feces, kidney, mammary gland, fat, and placenta in dams and in both maternal and fetal blood, brain, and liver. Cis- and trans-permethrin were quantified in fetal blood and tissues, with higher concentrations for the cis-isomer. The pPBPK model was fitted to the toxicokinetic maternal and fetal data in a Bayesian framework. Several parameters were adjusted, such as hepatic clearances, partition coefficients, and intestinal absorption. Our work allowed to estimate the prenatal exposure to permethrin in rats, especially in the fetal brain, and to quantitatively estimate the placental transfer. These transfers could be extrapolated to humans and be incorporated in a human pPBPK model to estimate the fetal exposure to permethrin from biomonitoring data.

Keywords: PBPK model; brain; fetus; permethrin; pesticides; pregnancy; pyrethroids; rat.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Physiologically based pharmacokinetic model of cis- and trans-permethrin in pregnant rats and fetuses.
Figure 2
Figure 2
Measured concentrations (squares) and toxicokinetic profiles estimated with the physiologically based pharmacokinetic model (solid line) of cis-permethrin in pregnant rats at GD1, GD15, and GD20. The gray dotted line stands for the limit of quantification.
Figure 3
Figure 3
Measured concentrations (dots) and toxicokinetic profiles estimated with the physiologically based pharmacokinetic model (solid line) of trans-permethrin in pregnant rats at GD1, GD15, and GD20. The gray dotted line stands for the limit of quantification.
Figure 4
Figure 4
Measured concentrations of cis-permethrin (squares) and trans-permethrin (dots) and toxicokinetic profiles estimated with the physiologically based pharmacokinetic model (solid lines) in the placenta (A) and fetal tissues (B). Mean values ± SD for n = 4 at each time point except for the point marked with an asterisk (n = 1). The gray dotted line stands for the limit of quantification.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Saillenfait A-M, Ndiaye D, Sabaté J-P. Pyrethroids: exposure and health effects – an update. Int J Hyg Environ Health. (2015) 218:281–92. 10.1016/j.ijheh.2015.01.002 - DOI - PubMed
    1. Feo ML, Eljarrat E, Barceló D, Barceló D. Determination of pyrethroid insecticides in environmental samples. TrAC Trends Anal Chem. (2010) 29:692–705. 10.1016/j.trac.2010.03.011 - DOI - PubMed
    1. Weston DP, Holmes RW, You J, Lydy MJ. Aquatic toxicity due to residential use of pyrethroid insecticides. Environ Sci Technol. (2005) 39:9778–84. 10.1021/es0506354 - DOI - PubMed
    1. 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. 10.1289/ehp.01109213 - DOI - PMC - PubMed
    1. Dereumeaux C, Saoudi A, Pecheux M, Berat B, de Crouy-Chanel P, Zaros C, et al. . Biomarkers of exposure to environmental contaminants in French pregnant women from the Elfe cohort in 2011. Environ Int. (2016) 97:56–67. 10.1016/j.envint.2016.10.013 - DOI - PubMed

LinkOut - more resources