Computational risk assessment framework for the hazard analysis of bisphenols and quinone metabolites

Bisphenol A (BPA) is a widely used chemical in plastics but its proven harmful effects has led to the replacement and production of its analogs that might also induce hazard as well as associated risks. To elucidate the adverse impact of the BPA analogs, a comprehensive computational framework is developed which applies toxicogenomics aligned with Density Functional Theory (DFT) and Molecular Dynamics (MD) based approaches to understand the toxic potential of quinone metabolites of Bisphenol F (BPF) and 3,3'-dimethylbisphenol A (DMBPA). The obtained results indicate a similar chemical reactivity profile for these metabolites of bisphenols to BPA metabolite. MD simulation revealed that the quinone metabolites tend to interact with the DNA comprising hydrogen bonding, van der Waals forces, and electrostatic interactions as an onset for covalent binding to adduct formation. Structural analysis suggests that interactions with DC9, DG10, DG16, DA17, DA18, and DT19 play a crucial role in stabilizing the quinone metabolite in the interactive pocket of DNA. These observations are demonstrating that BPF and DMBPA have the potential to impose genotoxicity via forming the quinone metabolite adducts. Combination of DFT and MD-based computational approaches providing a structure-activity-toxicity spectrum of chemicals can serve for the purpose of risk assessment.