Estrogenic activity of impurities in industrial grade bisphenol A

The estrogenicities of 10 compounds found as impurities in industrial grade bisphenol A (BPA) were measured by yeast two-hybrid assays incorporating the human estrogen receptor alpha (hER alpha) or the medaka fish (Oryzias latipes) estrogen receptor alpha (medER alpha). Five impurities showed greater activity than BPA itself in an agonist assay for hERa. p-Cumylphenol, the most active of the impurities in the hER alpha assay, was 12 times as active as BPA. The REC10 (10 % relative effective concentration: 10 % of the activity of 10(-8)M 17 beta-estradiol) was 710 nM. Five impurities showed greater activity than BPA in an agonist assay for medER alpha: 4,4'-(1,3-dimethylbutylidene) bisphenol and 2-(4'-hydroxyphenyl)-2,4,4-trimethylchroman were nearly equipotent and 9 times as active as BPA, and the REC10 values of these compounds in the medERa assay were 280 and 320 nM, respectively. Comparison of the experimentally determined estrogenicities of mixtures of BPA and 4,4'-(1,3-dimethylbutylidene) bisphenol and those calculated by the concentrations addition (CA) method confirmed the suitability of the method for the prediction of the estrogenicities of the mixtures of BPA and its phenolic analogues. The measured estrogenicities of four samples of industrial grade BPA and laboratory grade (pure) BPA were not significantly different in either the hER alpha assay or the medER alpha assay (p > 0.05 in each case). We conclude that the impurities in industrial grade BPA, although some are of much higher estrogenic activity than BPA itself, do not significantly increase the estrogenicity of the industrial compound and therefore do not increase possible adverse health effects from such activity.