ArticleEnvironmental health perspectives2019
Developmental Toxicity Assessment of Piperonyl Butoxide Exposure Targeting Sonic Hedgehog Signaling and Forebrain and Face Morphogenesis in the Mouse: An
Article in Environmental health perspectives, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Early-Stage Screening of Piperonylic Acid Analogues and Their Salts as Synergists for the Class of Pyrethroid Insecticides.ACS omega · 2026Article
- Combined Effects of Dinotefuran and Piperonyl Butoxide on Behavioral Development in an FBirth defects research · 2026Article
- Computational Mapping of Hedgehog Pathway Kinase Module Predicts Node-Specific Craniofacial Phenotypes.Genes · 2026Article
- Metabolic stability and effects of microsomal enzymes on the activity of the sonic hedgehog pathway inhibitor piperonyl butoxide.Toxicology in vitro : an international journal published in association with BIBRA · 2026Article
- Hedgehog pathway disruption alters urothelial differentiation and continence mechanisms in the female mouse lower urinary tract.American journal of physiology. Renal physiology · 2026Article
- A cell-based Sonic Hedgehog signaling transduction system to identify additive and synergistic chemical interactions.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.American journal of human genetics · 2025Article
- Examining the Neurodevelopmental Impact of Sonic Hedgehog Pathway Inhibition in Mice.Birth defects research · 2025Article
- Examination of piperonyl butoxide developmental toxicity as a Sonic hedgehog pathway inhibitor targeting limb and palate morphogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2024Article
- Disruption of DNA methylation-mediated cranial neural crest proliferation and differentiation causes orofacial clefts in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pharmacokinetic analysis of acute and dietary exposure to piperonyl butoxide in the mouse.Toxicology reports · 2023Article
- Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate.HGG advances · 2023Article
- Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate.medRxiv : the preprint server for health sciences · 2023Article
- High-throughput detection of craniofacial defects in fluorescent zebrafish.Birth defects research · 2023Article
- Gene-alcohol interactions in birth defects.Current topics in developmental biology · 2023Article
- Gene-environment interactions in birth defect etiology: Challenges and opportunities.Current topics in developmental biology · 2023Review
- Brain Organization and Human Diseases.Cells · 2022Review
- Response to Osimitz and Droege, 2021.Chemosphere · 2022Article
- Analysis of Gene-Environment Interactions Related to Developmental Disorders.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPiperonyl butoxide (PBO) is a pesticide synergist used in residential, commercial, and agricultural settings. PBO was recently found to inhibit Sonic hedgehog (Shh) signaling, a key developmental regulatory pathway. Disruption of Shh signaling is linked to birth defects, including holoprosencephaly (HPE), a malformation of the forebrain and face thought to result from complex gene-environment interactions.
objectivesThe impact of PBO on Shh signaling
methodsThe influence of PBO on Shh pathway transduction was assayed in mouse and human cell lines. To examine its teratogenic potential, a single dose of PBO (
resultsPBO attenuated Shh signaling DISCUSSION: These findings demonstrate that prenatal PBO exposure can cause overt forebrain and face malformations or neurodevelopmental disruptions with subtle or no craniofacial dysmorphology in mice. By targeting Shh signaling as a sensitive mechanism of action and examining gene-environment interactions, this study defined a lowest observable effect level for PBO developmental toxicity in mice more than 30-fold lower than previously recognized. Human exposure to PBO and its potential contribution to etiologically complex birth defects should be rigorously examined. https://doi.org/10.1289/EHP5260.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.