title: Effect of estrogenic binary mixtures in the yeast estrogen screen (YES).
abstract: Endocrine disrupting compounds (EDCs) of natural or synthetic origin can interfere with the balance of the hormonal system, either by altering hormone production, secretion, transport, or their binding and consequently lead to an adverse outcome in intact animals. An important aspect is the prediction of effects of combined exposure to two or more EDCs at the same time. The yeast estrogen assay (YES) is a broadly used method to assess estrogenic potential of chemicals. Besides exhibiting good predictivity to identify compounds which interfere with the estrogen receptor, it is easy to handle, rapid and therefore allows screening of a large number of single compounds and varying mixtures. Herein, we applied the YES assay to determine the potential combination effects of binary mixtures of two estrogenic compounds, bisphenol A and genistein, as well as one classical androgen that in vitro also exhibits estrogenic activity, trenbolone. In addition to generating data from combined exposure, we fitted these to a four-parametric logistic dose-response model. As all compounds tested share the same mode of action dose additivity was expected. To assess this, the Loewe model was utilized. Deviations between the Loewe additivity model and the observed responses were always small and global tests based on the whole dose-response data set indicated in general a good fit of the Loewe additivity model. At low concentrations concentration additivity was observed, while at high concentrations, the observed effect was lower than additivity, most likely reflecting receptor saturation. In conclusion, our results suggest that binary combinations of genistein, bisphenol A and trenbolone in the YES assay do not deviate from expected additivity.
authors.affiliation: BASF SE Experimental Toxicology and Ecology, Carl-Bosch Str. 38, 67056 Ludwigshafen am Rhein, Germany.
authors.forename: Tzutzuy
authors.initials: T
authors.lastname: Ramirez
authors.affiliation: BASF SE Scientific Computing, Carl-Bosch Str. 38, 67056 Ludwigshafen am Rhein, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buechse
authors.affiliation: BASF SE Experimental Toxicology and Ecology, Carl-Bosch Str. 38, 67056 Ludwigshafen am Rhein, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Dammann
authors.affiliation: BASF SE Product Safety, Carl-Bosch Str. 38, 67056 Ludwigshafen am Rhein, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Melching-Kollmuß
authors.affiliation: BASF SE Experimental Toxicology and Ecology, Carl-Bosch Str. 38, 67056 Ludwigshafen am Rhein, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Woitkowiak
authors.affiliation: BASF SE Experimental Toxicology and Ecology, Carl-Bosch Str. 38, 67056 Ludwigshafen am Rhein, Germany. Electronic address: bennard.ravenzwaay@basf.com.
authors.forename: Bennard
authors.initials: B
authors.lastname: van Ravenzwaay
mesh_terms: D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D019833:Genistein / Q000008:administration & dosage / Q000633:toxicity*; D008954:Models, Biological; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D014204:Trenbolone Acetate / Q000008:administration & dosage / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D019833:Genistein; D010636:Phenols; D011960:Receptors, Estrogen; D014204:Trenbolone Acetate; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Endocrine active compounds; Estrogenic mixtures; Genistein; Loewe additivity model; Trenbolone; Yeast based assay