Integration of Computational Toxicology, Toxicogenomics Data Mining, and Omics Techniques to Unveil Toxicity Pathways

Growing numbers of synthetic chemicals have potential endocrine-disrupting effects and cause ecological health risks. However, the primary toxicity pathways mechanisms endocrine disruption are poorly understood existing risk assessment relies heavily on animal testing. Database mining, omics technology, computer simulation can serve as an alternative approach to explore by building adverse outcome (AOPs). The present study took a case thyroid interference with triphenyl phosphate (TPP) explain toxic at levels from submolecules cells utilizing AOP framework developed multiple techniques. This retrieved data comparative toxicogenomics database (CTD) screened out core gene. Molecular dynamics (MD) analysis was used configuration changes confirm molecular initiating event (MIE). transcriptomic further utilized supplement relationships between MIEs key events (KEs) AOP. hormone receptor beta (THRB) identified gene submolecular levels. MD found that C-terminal helix 12 (H12) β (TRβ) were discovered MIE. extended related KE1 subcellular level, such in expression for coding cycle regulation (CCND1), inflammatory response (IL1A IL6), cell proliferation apoptosis (BAD, TP53, CASP9). Then, KE2 cellular apoptosis, control, influenced accordingly. As result, these alterations led disorder outcomes. provided efficient way facilitate complement possible AOPs brought new insights into understanding emerging chemicals.