Maternal and fetal tissue distribution of α-cypermethrin and permethrin in pregnant CD-1 mice

Abstract

Pyrethroid insecticides are widely used throughout agriculture and household products. Recent studies suggest that prenatal exposure to these insecticides may adversely affect fetal development; however, little is known about the distribution of these chemicals in pregnant animals. The present study aimed to address this gap in knowledge by investigating the distribution of two commonly used pyrethroid insecticides, permethrin and α-cypermethrin, in maternal and fetal tissues of pregnant CD-1 mice. Dams were dosed from gestational days 6 to 16 via oral gavage with permethrin (1.5, 15, and 50 mg/kg), α-cypermethrin (0.3, 3, and 10 mg/kg), or corn oil vehicle. Pyrethroid levels were determined in gestational day 16 tissues collected 90 min after the final dose was administered. Across maternal tissues, levels of both pyrethroids were the highest in maternal ovaries, followed by liver and brain, respectively. In addition, levels of both pyrethroids in maternal tissues and placenta were significantly higher than those in the fetal body and amniotic fluid, suggesting that these compounds may exhibit low transfer across the mouse placenta. While additional toxicokinetic studies are needed to verify the time course of pyrethroids in the fetal compartment, these findings support investigation into indirect modes of action relevant to the effects of pyrethroids on mammalian fetal development.

Keywords: Fetal; Placenta; Pregnancy; Pyrethroid; Tissue distribution.

Fig. 1.

Levels of α-cypermethrin and permethrin in maternal serum of pregnant mice after exposure GD6-16. Concentrations were measured in samples taken 90 min after the final dose was administered on GD16. Means and standard deviations of each pyrethroid are represented on a logarithmic scale (left) and proportional to the dose administered (right) (n = 10 samples per group).

Fig. 2.

Levels of α-cypermethrin in maternal and fetal tissues following exposure GD6-16. Concentrations reported as mean ± standard deviation (n = 9–10 samples per group). Ovary samples were pooled within each group and are reported as n = 1. Levels are represented on (A) a logarithmic scale and (B) plotted against maternal serum concentrations. Maternal serum samples were averaged and plotted against pooled ovary samples for correlation assessment. (****p < 0.0001, ***p < 0.001 for correlations).

Fig. 3.

Levels of permethrin in maternal and fetal tissues following exposure GD6-16. Concentrations reported as mean ± standard deviation (n = 9–10 samples per group). Ovary samples were pooled within each group and are reported as n = 1. Levels are represented on (A) a logarithmic scale and (B) plotted against maternal serum concentrations. Maternal serum samples were averaged and plotted against pooled ovary samples for correlation assessment. (****p < 0.0001 for correlations).

Fig. 4.

Levels of α-cypermethrin and permethrin in tissues relative to maternal serum concentration following exposure GD6-16. Data represent mean ± standard deviation (n = 29–30 dams per pyrethroid for liver, brain, placenta, and fetal body). (**p < 0.01, ****p < 0.0001).

Fig. 5.

Ratio of cis to trans permethrin isomers in maternal and fetal tissues after exposure GD6-16. Data represent mean ± standard deviation (n = 9–10 dams per dose) (**p < 0.01, ***p < 0.001).

Fig. 6.

Correlation between placenta and fetal body levels of (A) α-cypermethrin and (B) permethrin after exposure GD6-16 (****p < 0.0001).