Endocrine disruptors in e-waste dismantling dust: In silico prediction of mixture-induced reproductive toxicity mechanisms

The constant exposure of humans to a mixture of low doses of toxic substances, emerging from the daily emission of toxic dust containing various metals and organic compounds in electrical and electronic waste (e-waste) recycling areas, poses potential harmful effects on health and the environment. While individually recognized as endocrine disruptors affecting hormonal balance, the combined impact of these toxic substances in a mixture remains insufficiently explored, particularly in relation to reproductive health. Thus, the aim of this in silico analysis was to: (i) assess the relationship between the exposure to a mixture of DBDE, DBDPE, TBBPA, Pb, Cd and Ni and development of male and female reproductive system disorders; and (ii) demonstrate the ability of in silico toxicogenomic tools in revealing the potential molecular mechanisms involved in the mixture toxicity. As the main data-mining tool, Comparative Toxicogenomics Database (CTD) was used, along with the ToppGene Suite portal and GeneMANIA online server. Our analysis identified 5 genes common to all the investigated substances and linked to reproductive system disorders. Notably, the most prominent interactions among these genes were physical interactions (77.64 %). Pathway enrichment analysis identified oxidative stress response as the central disrupted molecular pathway linked to reproductive pathology in the investigated mixture, while our chemical-phenotype CTD analysis uncovered additional affected pathways - apoptosis, hormonal regulation, and developmental functions. These findings highlight an increased risk of reproductive system disorders associated with the exposure to the investigated mixture of toxic substances in electronic waste recycling areas, emphasizing the urgent need for attention to address this environmental health concern. Hence, future laboratory studies should prioritize investigating the specific genes and common mechanisms identified in this study.