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Dioxybenzone is widely used in cosmetics and personal care products and frequently detected in multiple environmental media and human samples. However, the current understanding of the metabolic susceptibility of dioxybenzone and the potential endocrine disruption through its metabolites in mimicking human estrogens remains largely unclear. Here we investigated the in vitro metabolism of dioxybenzone, detected the residue of metabolites in rats, and determined the estrogenic disrupting effects of these metabolites toward estrogen receptor α (ERα). In vitro metabolism revealed two major metabolites from dioxybenzone, i.e., M1 through the demethylation of methoxy moiety and M2 through hydroxylation of aromatic carbon. M1 and M2 were both rapidly detected in rat plasma upon exposure to dioxybenzone, which were then distributed into organs of rats in the order of livers > kidneys > uteri > ovaries. The 100 ns molecular dynamics simulation revealed that M1 and M2 formed hydrogen bond to residue Leu387 and Glu353, respectively, on ERα ligand binding domain, leading to a reduced binding free energy. M1 and M2 also significantly induced estrogenic effect in comparison to dioxybenzone as validated by the recombinant ERα yeast two-hybrid assay and uterotrophic assay. Overall, our study revealed the potential of metabolic activation of dioxybenzone to induce estrogenic disrupting effects, suggesting the need for incorporating metabolic evaluation into the health risk assessment of benzophenones and their structurally similar analogs. Dioxybenzone was metabolized into two major metabolites via hydroxylation and demethylation, which exhibited higher binding affinity and agonistic activity toward ERα than dioxybenzone.

The present invention relates to compounds that have ultraviolet light absorbing properties, and which can also have mesogenic properties. The present invention also relates to compositions that include one or more such compounds, and to articles of manufacture that include one or more such compounds, such as optical elements that include an optical substrate and a layer that includes at least one compound of the present invention.