Long used in polycarbonate plastics, epoxy resin food-can liners, and thermal receipt paper, bisphenol A (BPA) has become a poster child for endocrine disruptors—compounds that mimic or interfere with the body’s hormones, such as estrogens and androgens. Many manufacturers have replaced BPA with alternatives in recent years, but dozens of BPA substitutes lack data on their potential estrogenic activity. Now, a new computer model provides a way to determine whether a BPA substitute shows high potential to bind the estrogen receptor and requires further testing for its endocrine disrupting effects (Chem. Res. Toxicol. 2015, DOI: 10.1021/acs.chemrestox.5b00243).
Huixiao Hong of the Food & Drug Administration’s National Center for Toxicological Research and his colleagues developed a model that assesses how well a compound orients itself with the estrogen receptor, and then estimates binding affinity by calculating how energetically favorable the binding is. The researchers trained the model by running it on 18 BPA substitutes that already have estrogenic activity data and two reference compounds: BPA itself and 17β-estradiol, a key female sex hormone.
When the researchers ran the model on 27 BPA substitutes that lacked experimental data on estrogenic activity, the model identified 11 that met the criteria for binding to the receptor. Many compounds were predicted as better potential binders than BPA, including tetrabromobisphenol A, used in plastics and as a flame retardant, and bis-(3-allyl-4-hydroxyphenyl)sulfone, used in thermal receipt paper.
Binding the receptor alone isn’t sufficient to make the compound an endocrine disruptor, the researchers note. But they add that the findings do suggest the need for additional studies of these compounds’ safety.