{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:56:23Z","timestamp":1790776583571,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Key R&D Plan of Ningxia Hui Autonomous Region","award":["2022BEG02027"],"award-info":[{"award-number":["2022BEG02027"]}]},{"award":["2022BEG02027"],"award-info":[{"award-number":["2022BEG02027"]}],"id":[{"id":"https:\/\/ror.org\/015bdn754","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2019s 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\u2014the core gene encoding the GABA synthesis rate\u2013limiting enzyme (glutamate decarboxylase)\u2014leading to an excitation\u2013inhibition 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\u2013OPFRs 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.<\/jats:p>","DOI":"10.3390\/ijms27198769","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:01:19Z","timestamp":1790773279000},"page":"8769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction of Adverse Outcome Pathway (AOP) for Triphenyl Phosphate (TPHP)\u2013Induced Autism Spectrum Disorder (ASD) and Risk Identification of Neurodevelopmental Toxicity of Aryl Organophosphorus Flame Retardants (OPFRs) Based on Multidimensional Bioinformatic Data"],"prefix":"10.3390","volume":"27","author":[{"given":"Yonghang","family":"Li","sequence":"first","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Kaidong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Ai","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Ge","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Public Health, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"},{"name":"Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, No. 1160, Shengli Street, Xingqing District, Yinchuan 750001, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133332","DOI":"10.1016\/j.jhazmat.2023.133332","article-title":"Exposure of male adult zebrafish (Danio rerio) to triphenyl phosphate (TPhP) induces eye development disorders and disrupts neurotransmitter system-mediated abnormal locomotor behavior in larval offspring","volume":"465","author":"Zhang","year":"2024","journal-title":"J. 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