Interaction of Polycyclic Musks and UV Filters with the Estrogen Receptor (ER), Androgen Receptor (AR), and Progesterone Receptor (PR) in Reporter Gene Bioassays

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Abstract
Two important ingredients of personal care products, namely polycyclic musk fragrances and UV filters, can be found in the environment and in humans. In previous studies, several compounds of both classes have been tested for their interaction with the estrogen receptor. Two polycyclic musk fragrances, namely AHTN and HHCB, turned out to be anti-estrogenic both in vitro and in vivo in a transgenic zebrafish assay. Several UV filters have been shown to exert estrogenic effects in vitro and in some in vivo studies. Here, we assessed the interaction of five polycyclic musk compounds and seven UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone (PR) receptor, using sensitive and specific reporter gene cell lines. Four polycyclic musks (AHTN, HHCB, AETT, and AHMI) were found to be antagonists toward the ERβ, AR and PR. The UV filters that showed estrogenic effects (benzophenone-3, Bp-3; 3-benzylidene camphor, 3-BC; homosalate, HMS; and 4-methylbenzylidene camphor, 4-MBC) were found to be antagonists toward the AR and PR. The ERα agonistic UV filter octyl-dimethyl-p-aminobenzoic acid (OD-PABA) did not show activity toward the AR and PR. Octyl methoxy cinnamate (OMC) showed weak ERα agonism, but potent PR antagonism. Butyl methoxydibenzoylmethane (B-MDM) only showed weak ERα agonism and weak AR antagonism. Most effects were observed at relatively high concentrations (above 1 μM); however, the anti-progestagenic effects of the polycyclic musks AHMI and AHTN were detected at concentrations as low as 0.01 μM. The activity of anti-progestagenic xenobiotics at low concentrations indicates the need to undertake more research to find out about the potential endocrine disrupting effects of these compounds in vivo.

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