Molecular and toxicological study of the plasticizers exposure-induced metabolic disorders

Plasticizers and food safety and the associated potential human health risk are important and of a global concern. Despite extensive evidence linking of plasticizers, particularly phthalate esters (PAEs) to metabolic disorders, their multi-target effects and molecular pathways remain poorly understood. Therefore, this study utilizes a novel integrated computational approach combining network toxicology and molecular docking to systematically investigate how PAEs in food packaging induce metabolic disorders. Four PAEs were analyzed through a compound-target-disease network linked to type II diabetes, obesity, and NAFLD. Key targets like B-cell lymphoma 2 (BCL2) and caspase-3 (CASP3) were identified, with enrichment analyses highlighting xenobiotic response, protein phosphorylation, advanced glycation end product-receptor for advanced glycation end product (AGE-RAGE) signaling, insulin resistance, and apoptosis pathways. The findings suggest PAEs disrupt metabolism via apoptosis, inflammation, protein kinase alterations, and neuroendocrine interference, underscoring the global health risks posed by endocrine disruptors from food packaging.