Phenone, Hydroxybenzophenone, and Branched Phenone Estrogen Receptor Binding and Vitellogenin Agonism in Rainbow Trout In Vitro Models

Introduction: Phenones and hydroxybenzophenones are widely used as ultraviolet radiation filters, and in the manufacturing of insecticides and pharmaceuticals. Understanding the estrogenic potential of these chemicals is of interest to the U.S. Environmental Protection Agency and other international environmental organizations. Materials and Methods: This study sequentially combined complementary in vitro rainbow trout estrogen receptor (rtER) binding and liver slice vitellogenin (Vtg) mRNA induction assays in the context of a defined estrogen receptor-mediated adverse outcome pathway. Results/Discussion: Cyclic phenones, branched phenones, and hydroxybenzophenones bound to rtER with relative potency ranging from no affinity to high binding affinity of 0.11%, and many induced Vtg gene expression in rainbow trout (rt) liver slices. In addition, cyclohexylphenylketone, which did not bind rtER binding in cytosol, was biotransformed within liver tissue to a chemical that induced Vtg expression. Conclusion: Cyclic phenones, branched phenones, and hydroxybenzophenones were estrogenic in these rt in vitro assays, therefore are potential endocrine disruptors.