In vitro estrogenic activity of representative endocrine disrupting chemicals mixtures at environmentally relevant...

Exposure to mixtures of endocrine disrupting compounds (EDCs) has been hypothesized to produce potential synergistic or antagonistic effects that can cause undesired effects that are not reflected by the individual compounds. In this study, the estrogenic activities of 11 EDCs of global environmental concern were systematically investigated using the yeast estrogen screen (YES). The contribution of the individual chemical to the total endocrine activity of environmentally relevant mixtures was evaluated. Compared to 17β-estradiol (E2) as a standard, estrone (E1), estriol (E3), ethinyl estradiol (EE2), bisphenol-A (BPA), and genistein (GEN) showed estrogenic effects, while dibutyl phthalate (DBP), n-butyl benzyl phthalate (BBP), Bis(2-ethylhexyl) phthalate (DEHP), nonyl phenol (NP) and 4-tert-octyl phenol (OP) showed anti-estrogenic effects. The 11 EDCs mixture at a constant environmentally relevant ratio also showed estrogenic activity. The mixtures data were fit to concentration addition (CA), response addition (RA) and interaction (IR) models, respectively. The IR model was not statistically different from the observed value and better predicted results than the CA model for mixtures of all 11 compounds. For the mixtures with the 6 estrogenic compounds only, additive effects were observed, and the data were well predicted by the CA and IR models. Further, in the 11 EDCs mixture the presence of EE2 at an environmentally relevant concentration did not increase the estrogenic activity as compared to a 10 EDCs mixture without EE2.