Estrogenic activities of UV stabilizers used in food contact plastics and benzophenone derivatives tested by the yeast two-hybrid assay

UV stabilizers used in food contact plastics were tested for their estrogenic activity by the yeast two-hybrid assay. Among 11 kinds of UV stabilizers, 2-hydroxy- 4-methoxybenzophenone and 2,2'-dihydroxy-4-methoxybenzophenone displayed estrogenic activity, while salicylate, benzoate and benzotriazole derivatives and a benzophenone derivative had no activity. Therefore, benzophenone and 19 kinds of hydroxylated derivatives were further studied. Of these, 15 chemicals showed estrogenic activity. The strongest activity was by 2,4-dihydroxybenzophenone, 4-hydroxy-4'-chlorobenzophenone, 4-hydroxybenzophenone and 2,3,4-trihydroxybenzophenone. Their activities were stronger than that of bisphenol A which was recognized as a potential endocrine disruptor. The following structure-activity relationships of benzophenones were obtained. The activity of the benzophenones with a hydroxyl group at the 3 or 4-position was positive and rather strong, though that of other benzophenones without a hydroxyl group at the 3 or 4-position was negative or weakly positive. The effect of the hydroxyl group in the phenol moiety were in order of 4- > 3- much greater than 2-position. A hydroxyl group added at the 2-position of the 4-hydroxylated benzene ring enhanced the activity. On the other hand, a hydroxyl group added to the benzene ring of the hydrophobic moiety reduced the binding, while the chloro group enhanced it. Some of these relationships might possibly hold for other estrogenic chemicals that possess two benzene rings.