Examining the developmental toxicity of piperonyl butoxide as a Sonic hedgehog pathway inhibitor.
Birth defects
Gene-environment
Pesticides
Piperonyl butoxide
Sonic hedgehog
Journal
Chemosphere
ISSN: 1879-1298
Titre abrégé: Chemosphere
Pays: England
ID NLM: 0320657
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
20
07
2020
revised:
17
09
2020
accepted:
18
09
2020
pubmed:
3
10
2020
medline:
23
12
2020
entrez:
2
10
2020
Statut:
ppublish
Résumé
Piperonyl butoxide (PBO) is a semisynthetic chemical present in hundreds of pesticide formulations used in agricultural, commercial, and residential settings. PBO acts as a pesticide synergist by inhibiting insect cytochrome P450 enzymes and is often present at much higher concentrations than active insecticidal ingredients. PBO was recently discovered to also inhibit Sonic hedgehog (Shh) signaling, a key molecular pathway in embryonic development and in brain and face morphogenesis. Recent animal model studies have shown that in utero PBO exposure can cause overt craniofacial malformations or more subtle neurodevelopmental abnormalities. Related adverse developmental outcomes in humans are etiologically heterogeneous, and, while studies are limited, PBO exposure during pregnancy has been linked to neurodevelopmental deficits. Contextualized in PBO's newly recognized mechanism as a Shh signaling inhibitor, these findings support more rigorous examination of the developmental toxicity of PBO and its potential contribution to etiologically complex human birth defects. In this review, we highlight environmental sources of human PBO exposure and summarize existing animal studies examining the developmental impact of prenatal PBO exposure. Also presented are critical knowledge gaps in our understanding of PBO's pharmacokinetics and potential role in gene-environment and environment-environment interactions that should be addressed to better understand the human health impact of environmental PBO exposure.
Identifiants
pubmed: 33007564
pii: S0045-6535(20)32609-6
doi: 10.1016/j.chemosphere.2020.128414
pmc: PMC9158378
mid: NIHMS1809479
pii:
doi:
Substances chimiques
Hedgehog Proteins
0
Insecticides
0
Pesticides
0
Piperonyl Butoxide
LWK91TU9AH
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
128414Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES026819
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007015
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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