Construction of Adverse Outcome Pathway (AOP) for Triphenyl Phosphate (TPHP)–Induced Autism Spectrum Disorder (ASD) and Risk Identification of Neurodevelopmental Toxicity of Aryl Organophosphorus Flame Retardants (OPFRs) Based on Multidimensional Bioinformatic Data
- 1School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China
- 2Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China
Abstract
Triphenyl phosphate (TPHP) is a widely used plasticizer and organophosphate flame retardant extensively applied in various industrial and consumer products. Due to its pervasive environmental exposure and detection in human samples such as amniotic fluid and breast milk, TPHP has become a pollutant of significant concern in recent years for its potential neurodevelopmental impacts on humans. This study employed a multimethod approach integrating network toxicology, transcriptomics, in silico gene knockout, molecular docking, and molecular dynamic simulations to investigate TPHP’s potential toxic role in autism spectrum disorder (ASD). An adverse outcome pathway (AOP) was constructed, revealing that TPHP exposure may induce and exacerbate ASD by downregulating GAD1—the core gene encoding the GABA synthesis rate–limiting enzyme (glutamate decarboxylase)—leading to an excitation–inhibition imbalance in the brain. The batch molecular docking of 85 organophosphate flame retardants (OPFRs) (widely detected in human and biological matrices) with the GAD1 protein identified aryl–OPFRs as disruptors targeting GAD1 to induce neurodevelopmental toxicity. In summary, this research provides mechanistic insights into how TPHP promotes ASD progression and offers a valuable chemical reference for assessing the neurodevelopmental toxicity of OPFRs.
Related
- Identification of Shared Hub Genes between Endometriosis and Ovarian Clear Cell Carcinoma Using Integrative Bioinformatic Analysis
- Construction and validation of an identification model for frailty in maintenance hemodialysis patients using multiple machine learning algorithms: a cross-sectional study of retrospectively collected data
- Human CYP1A2 metabolism of organophosphorus pesticides and nerve agent surrogates
- Construction of a prognostic model and immune landscape analysis for lung adenocarcinoma utilizing a bioinformatics signature derived from acrolein-related genes, and identification of associated subtypes.
- Construction and validation of a unified 3D convolutional neural network framework for automated identification of cervical spinal cord injury based on CT imaging
BibTeX
@article{li2026construction,
title = {{Construction of Adverse Outcome Pathway (AOP) for Triphenyl Phosphate (TPHP)–Induced Autism Spectrum Disorder (ASD) and Risk Identification of Neurodevelopmental Toxicity of Aryl Organophosphorus Flame Retardants (OPFRs) Based on Multidimensional Bioinformatic Data}},
author = {Yonghang Li and Kaidong Wang and Ai Qi and Qi Liu and Ge Shi and Min Huang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198769},
url = {https://www.mdpi.com/1422-0067/27/19/8769},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Construction of Adverse Outcome Pathway (AOP) for Triphenyl Phosphate (TPHP)–Induced Autism Spectrum Disorder (ASD) and Risk Identification of Neurodevelopmental Toxicity of Aryl Organophosphorus Flame Retardants (OPFRs) Based on Multidimensional Bioinformatic Data
AU - Yonghang Li
AU - Kaidong Wang
AU - Ai Qi
AU - Qi Liu
AU - Ge Shi
AU - Min Huang
PY - 2026
DA - 2026/09/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198769
UR - https://www.mdpi.com/1422-0067/27/19/8769
AB - Triphenyl phosphate (TPHP) is a widely used plasticizer and organophosphate flame retardant extensively applied in various industrial and consumer products. Due to its pervasive environmental exposure and detection in human samples such as amniotic fluid and breast milk, TPHP has become a pollutant of significant concern in recent years for its potential neurodevelopmental impacts on humans. This study employed a multimethod approach integrating network toxicology, transcriptomics, in silico gene knockout, molecular docking, and molecular dynamic simulations to investigate TPHP’s potential toxic role in autism spectrum disorder (ASD). An adverse outcome pathway (AOP) was constructed, revealing that TPHP exposure may induce and exacerbate ASD by downregulating GAD1—the core gene encoding the GABA synthesis rate–limiting enzyme (glutamate decarboxylase)—leading to an excitation–inhibition imbalance in the brain. The batch molecular docking of 85 organophosphate flame retardants (OPFRs) (widely detected in human and biological matrices) with the GAD1 protein identified aryl–OPFRs as disruptors targeting GAD1 to induce neurodevelopmental toxicity. In summary, this research provides mechanistic insights into how TPHP promotes ASD progression and offers a valuable chemical reference for assessing the neurodevelopmental toxicity of OPFRs.
SN - 1422-0067
ER -