Effect of estrogenic binary mixtures in the XXXX @entity172 screen (YES).

@entity172 @entity670 @entity28189 @entity342 @entity375 @entity8241
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 @entity375 @entity172 assay (YES) is a broadly used method to assess estrogenic potential of chemicals. Besides exhibiting good predictivity to identify compounds which interfere with the @entity172 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, @entity8241 and @entity670 , as well as one classical @entity342 that in vitro also exhibits estrogenic activity, @entity28189 . 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 @entity670 , @entity8241 and @entity28189 in the YES assay do not deviate from expected additivity.
