Integrated assessment of bisphenols, phthalates, and biocides for estrogenic and androgenic endocrine-disrupting properties

The integrated assessment of estrogenic and androgenic endocrine disruption using a combination of receptor dimerization and transactivation assays is an effective approach for providing information the mechanistic action of chemical compounds that disrupt estrogen and androgen signaling pathways at the cellular level. This study integratedly evaluated the estrogenic and androgenic endocrine-disrupting properties of a total of 29 chemicals, including representative bisphenols, phthalates, and biocides, which are commonly exposed to humans. As a result, most bisphenols showed estrogenic agonist activity through transactivation via dimerization of estrogen receptors alpha and beta, while also exhibiting androgenic antagonist activity by inhibiting dihydrotestosterone-induced transactivation through interference with androgen receptor dimerization. Most phthalates also exhibited estrogenic agonist activity through transactivation via dimerization of estrogen receptors alpha and beta, and only some of them showed androgenic antagonist activity by interfering with androgen receptor dimerization and inhibiting dihydrotestosterone-induced transactivation. Biocides showed estrogenic and androgenic endocrine-disrupting properties through various mechanisms depending on their structural diversity. This integrated assessment effectively provided clues to the mechanism of action of endocrine-disrupting chemicals in estrogen and androgen signaling pathways at the cellular level, based on the adverse outcome pathway framework.