Identifying potential thyroid hormone disrupting effects among diphenyl ether structure pesticides and their metabolites in silico

The environmental and dietary pesticide exposures can cause thyroid hormones (THs) disorders, which are associated with the high incidence of thyroid diseases worldwide. The structures of diphenyl ether pesticides and their metabolites are very similar to the structure of THs. Based on this, in silico molecular simulation approaches were used to predict, screen, evaluate and identify the binding interactions of 98 diphenyl ether structure pesticides and their metabolites (DEPMs) with 10 THs related proteins in the study. The research results indicated that these DEPMs such as fluoroglycofen (FOG), rafoxanide, diclofop, ethoxyfen and difenopenten were considered to have the greater potentials to interfere with the related proteins of THs biosynthesis, blood transport, receptor binding and metabolism. And FOG can interact with thyroid hormone receptor beta (TR beta) to form non-bond interactions. Furthermore, the results of molecular dynamics simulations showed that there were strong and stable interactions between FOG and TR beta. These results suggested that the herbicide FOG was likely to disturb THs nuclear receptor. And benzene rings and hydrophobic groups might be the characteristic chemical functional groups for DEPMs to disrupt TR beta. The relevant results of this study can be used to provide references for environmental toxicology evaluation, food safety risk assessment, and formulation and revision of pesticides and their metabolites residue limits in agricultural products and food.