An analytical survey of benzotriazole UV stabilizers in plastic products and their endocrine-disrupting potential via human estrogen and androgen receptors

Benzotriazole UV stabilizers (BUVSs) are added to various materials to prevent damage from UV-irradiation. Recently, there has been great concern regarding the endocrine-disrupting effects of exposure to microplastic-derivative BUVSs in particular. In this study, we measured the concentrations of nine representative BUVSs in the plastic bottle caps of 10 beverages, 4 food packages, and 4 plastic shopping bags purchased from Japanese grocery stores by GC-MS analysis, and found that eight BUVSs, except for 2-(3,5-di-tert-butyl-2-hydroxyphenyl)-2H-benzotriazole (UV-320), were detected from these plastic products. In particular, 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) and 2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chlorobenzotriazole (UV-326) were detected from all the bottle caps at concentrations in the order of ng/g. In addition, we characterized the agonistic and/or antagonistic activities against human estrogen receptors (ERα/β) and androgen receptor (AR) of 13 BUVSs. Results revealed that, among the 13 BUVSs, UV-P, 2-(5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-PS), 2-[2-hydroxy-5-[2-(methacryloyloxy)ethyl]phenyl]-2H-benzotriazole (UV-090) and 2-(2-hydroxy-5-tert-octylphenyl)-benzotriazole (UV-329) showed ERα and/or ERβ agonistic activity, with UV-P being the most potent based on these assays. On the other hand, UV-320 and 2-(3-s-butyl-5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-350) showed both ERα and ERβ antagonistic activities, and 2-(3,5-di-tert-amyl-2-hydroxylphenyl) benzotriazole (UV-328) and UV-329 acted as ERβ antagonists. In the AR assay, UV-P and 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV-9) showed AR antagonistic activity although none of the test compounds showed AR agonistic activity. Taken together, our findings suggest that a series of BUVSs are present in our environments via plastic materials and several of these compounds possess endocrine-disrupting potential, such as ERα/β agonistic and/or antagonistic activity and AR antagonistic activity. UV-P and its structurally similar compounds, in particular, appear to be a cause for concern.