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

## TL;DR

This study explores how dioctyl terephthalate (DOTP) may contribute to allergic airway diseases through immune and apoptotic pathways, identifying key genes and potential health risks.

## Contribution

The study introduces a composite approach combining network toxicology and machine learning to uncover DOTP's role in allergic airway diseases.

## Key findings

- DOTP showed potential toxicity, including carcinogenicity and nephrotoxicity.
- DOTP shared 136 targets with allergic diseases, mainly involved in immune and apoptotic pathways.
- Key genes like EGFR, BCL2, CFTR, SYK, and C3AR1 were identified as core targets affected by DOTP.

## Abstract

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).

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.

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.

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.