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

Elser, Benjamin; Simonsen, Derek; Lehmler, Hans‐Joachim; Stevens, Hanna E.

doi:10.1016/j.envadv.2022.100239

Cited by 8 publications

(3 citation statements)

References 63 publications

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“…The predicted accumulation in human from the same 1 mg/kg dose using physiologically based models is approximately twice this concentration, suggesting an increased sensitivity ( 78 ). By comparison, pregnant mice exposed to 1.5 mg/kg permethrin showed serum concentrations of 260 ng/mL ( 79 ). A study on deltamethrin levels in blood in the general population in Beijing showed a range of 0–17.34 ng/mL ( 80 ), and a separate study in pregnant Chinese women showed an average level in blood of 39 ng/mL ( 81 ).…”

Section: Discussionmentioning

confidence: 99%

Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice

et al. 2023

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Neurodevelopmental disorders (NDDs) are a widespread and growing public health challenge, affecting as many as 17% of children in the United States. Recent epidemiological studies have implicated ambient exposure to pyrethroid pesticides during pregnancy in the risk for NDDs in the unborn child. Using a litter-based, independent discovery–replication cohort design, we exposed mouse dams orally during pregnancy and lactation to the Environmental Protection Agency's reference pyrethroid, deltamethrin, at 3 mg/kg, a concentration well below the benchmark dose used for regulatory guidance. The resulting offspring were tested using behavioral and molecular methods targeting behavioral phenotypes relevant to autism and NDD, as well as changes to the striatal dopamine system. Low-dose developmental exposure to the pyrethroid deltamethrin (DPE) decreased pup vocalizations, increased repetitive behaviors, and impaired both fear conditioning and operant conditioning. Compared with control mice, DPE mice had greater total striatal dopamine, dopamine metabolites, and stimulated dopamine release, but no difference in vesicular dopamine capacity or protein markers of dopamine vesicles. Dopamine transporter protein levels were increased in DPE mice, but not temporal dopamine reuptake. Striatal medium spiny neurons showed changes in electrophysiological properties consistent with a compensatory decrease in neuronal excitability. Combined with previous findings, these results implicate DPE as a direct cause of an NDD-relevant behavioral phenotype and striatal dopamine dysfunction in mice and implicate the cytosolic compartment as the location of excess striatal dopamine.

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Section: Discussionmentioning

confidence: 99%

Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice

et al. 2023

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“…For example, in adult rats, a 1 mg/kg dose of deltamethrin resulted in a serum concentration of 56 ng/mL 58 , with human models predicting double these levels 59 . Comparatively, pregnant mice exposed to 1.5 mg/kg permethrin had serum concentrations of 260 ng/mL 39 . Deltamethrin levels in the general population in Beijing ranged from 0 to 17.34 ng/mL 60 , while pregnant Chinese women had an average level of 39 ng/mL 61 .…”

Section: Discussionmentioning

confidence: 97%

“…We chose to focus on male offspring because both the behavioral and molecular outcomes of developmental pyrethroid exposure (DPE) have been male-biased, so the most significant changes in brain metabolism would be expected to occur in males. Deltamethrin readily penetrates all regions of the brain following acute oral exposure in mice, potentially affecting many brain regions 38 ; and following acute oral exposure in pregnant mice, the related pyrethroid permethrin crosses the placenta into the embryo, where it potentially accesses the entire developing brain 39 . We therefore selected the whole brain as our level of investigation in order to best represent major changes in brain metabolism across many brain regions and majority cell types.…”

Section: Introductionmentioning

confidence: 99%

Developmental pyrethroid exposure in mouse leads to disrupted brain metabolism in adulthood

Curtis,

Saferin,

Nguyen

et al. 2023

Preprint

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Environmental and genetic risk factors, and their interactions, contribute significantly to the etiology of neurodevelopmental disorders (NDDs). Recent epidemiology studies have implicated pyrethroid pesticides as an environmental risk factor for autism and developmental delay. Our previous research showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice causes male-biased changes in the brain and in NDD-relevant behaviors that persist into adulthood. Here, we used a metabolomics approach to determine the broadest possible set of metabolic changes in the adult male mouse brain caused by low-dose developmental pyrethroid exposure. Using a litter-based design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood and collected whole brain samples for untargeted high-resolution metabolomics analysis. Developmentally exposed mice had disruptions in 116 metabolites which clustered into pathways for folate biosynthesis, retinol metabolism, and tryptophan metabolism. Disrupted folate metabolism was confirmed using perturbagen analysis on split-sample transcriptomics data from the same mice, which identified a folate inhibitor as the drug causing the most similar effect to DPE. These results suggest that DPE directly disrupts folate metabolism in the brain, which may inform both prevention and therapeutic strategies.

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Assessing the ecological impact of pesticides/herbicides on algal communities: A comprehensive review

Narayanan,

Devarayan,

Verma

et al. 2024

Aquatic Toxicology

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

Cited by 8 publications

References 63 publications

Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice

Developmental pyrethroid exposure causes a neurodevelopmental disorder phenotype in mice

Developmental pyrethroid exposure in mouse leads to disrupted brain metabolism in adulthood

Assessing the ecological impact of pesticides/herbicides on algal communities: A comprehensive review

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