Deciphering the toxicological mechanism of airway allergic diseases caused by dioctyl terephthalate: a composite study.

BACKGROUND

Dioctyl terephthalate (DOTP), a common plasticizer alternative, has unclear immunotoxic effects on respiratory allergic diseases such as allergic rhinitis (AR), asthma (AS), chronic rhinosinusitis (CRS), and allergic bronchopulmonary aspergillosis (ABPA).

METHODS

We integrated network toxicology, target mining, bioinformatics, and machine learning to explore DOTP's potential role in allergic airway diseases. Shared targets were analyzed via PPI networks, enrichment analyses, immune profiling, single-cell data, and molecular docking. Key genes were validated in vitro using human airway epithelial cells.

RESULTS

DOTP showed potential toxicity including carcinogenicity and nephrotoxicity. It shared 136 targets with allergic diseases, mainly involved in immune and apoptotic pathways. EGFR, BCL2, CFTR, SYK, and C3AR1 were identified as core genes. DOTP showed strong binding to these targets and induced cytotoxicity and gene expression changes in epithelial cells.

CONCLUSION

DOTP may promote allergic airway diseases via immune-related and multi-target mechanisms. These findings highlight potential health risks of DOTP exposure and warrant further investigation.