Molecular modelling methods in food safety: Bisphenols as case study

Abstract Bisphenol A (BPA), a synthetic compound widely used as a building block for polycarbonate plastics, has been declared in the European Union (EU) as a substance of very high concern (SVHC). A series of BPA alternatives and derivatives (bisphenols/BPs) with similar physical-chemical properties have been produced and used by companies for substituting it. To evaluate the estrogenic and androgenic binding activity of 26 BPs, a non-statistical in silico approach has been applied. The results of molecular docking analyses applied on six different nuclear receptors (NRs) have revealed that: i) some BPA metabolites could lower the harmful effects of BPA exposure; ii) BPS is a lower interactor for all NRs, but it does not appear safer at all for androgen receptor (AR), for which its binding activity is found similar to a pharmacological anti-androgen; iii) only a BP has been found as a safer compound for all NRs considered. Moreover, molecular dynamic simulation of three BPs on ERα have revealed that the presence of negative hydrophobic interactions could induce a decrease in receptor activity. Overall, the present results demonstrate that in silico methods could be a valid approach to screen estrogenic and androgenic activity of food contact materials (FCMs).