ToxSci Advance Access published online on November 10, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfi035
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Institute for Risk Assessment Sciences, Utrecht University, PO Box 80176, 3508 TD, Utrecht, The Netherlands
* To whom correspondence should be addressed. 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 towards the ER
Accepted November 8, 2004
Endocrine Toxicology
Interaction of Polycyclic Musks and UV Filters with the Estrogen Receptor (ER), Androgen Receptor (AR) and Progesterone Receptor (PR) in Reporter Gene Bioassays
2 BioDetection Systems B.V., Badhuisweg 3, 1031 CM, Amsterdam, The Netherlands
Willem Seinen, E-mail: w.seinen{at}iras.uu.nl
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Abstract
, 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 towards the AR and PR. The ER
agonistic UV filter octyl-dimethyl-p-aminobenzoic acid (OD-PABA) did not show activity towards the AR and PR. Octyl methoxy cinnamate (OMC) showed weak ER
agonism, but potent PR antagonism. Butyl methoxydibenzoylmethane (B-MDM) only showed weak ER
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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