Estrogenic activity of benzotriazole UV stabilizers evaluated through in vitro assays and computational studies

Benzotriazole UV stabilizers (BUVs) are used in a variety of products to prevent yellowing and degradation. However, knowledge of the estrogenic activity of BUVs is still lacking. In the present study, a strategy combining in vitro assays and computational studies was adopted to evaluate the estrogenic activity of BUVs. 2-(2-Hydroxy-5-methlphenyl) benzotriazole (UV-P), 2-(5-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-PS), and 2-(3-Allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV-9) induced partial estrogenic activity while 2-(2-hydroxy-5-tert-octyl-phenyl)benzotriazole (UV-329), 2-(3-s-butyl-5-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-350), and 3-(2H-benzotriazolyl)-5- (1,1-di-methylethyl)-4-hydroxy-benzene-propanoic acid octyl esters (UV-384) showed no estrogenic activity in MVLN assays. The results of in vitro assays were in accord with the results of computational studies. Moreover, ICI 182,780 suppressed the estrogenic activity of BUVs both in the absence and presence of E₂, demonstrating that the estrogen responsive element (ERE) transcription activities of BUVs are generated through an estrogen receptor (ER) mediated pathway. Our findings suggest that the endocrine disruption effects of BUVs are a cause for concern.