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

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 ERbeta, 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 ERalpha 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 ERalpha agonism, but potent PR antagonism. Butyl methoxydibenzoylmethane (B-MDM) only showed weak ERalpha agonism and weak AR antagonism. Most effects were observed at relatively high concentrations (above 1 muM); however, the anti-progestagenic effects of the polycyclic musks AHMI and AHTN were detected at concentrations as low as 0.01 muM. 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.

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

“…Harvey and Darbre (2004) and Harvey and Everett (2006) have noted that all types of bodycare cosmetics applied to the skin (not just underarm cosmetics) can be a source of local oestrogenic chemical input to the breast and should be considered in risk assessments. Furthermore, there are also an increasing number of other ingredients in various cosmetics that have been shown to be endocrine active or oestrogenic [for example polycyclic musks (Gomez et al, 2005;Schreurs et al, 2005), UV ¼lters (Schlumpf et al, 2001;Inui et al, 2003;Koda et al, 2005), aluminium chlorhydrate (Darbre, 2006b), triclosan (Gee et al, 2008), phthalates (Jobling et al, 1995;Harris et al, 1997;Okubo et al, 2003), cyclosiloxanes (McKim et al, 2001;He et al, 2003)] and risk assessments should take into account mixture and combined repeated exposure effects.…”

“…Thus common coingredients in cosmetic formulations may interact in mixtures, resulting in higher skin and body burdens of parabens [and other endocrine active compounds common in cosmetics, e.g. phthalates (Jobling et al, 1995;Harris et al, 1997;Okubo et al, 2003), polycyclic musks (Gomez et al, 2005;Schreurs et al, 2005), UV ¼lters (Schlumpf et al, 2001;Inui et al, 2003;Janjua et al, 2004;Koda et al, 2005), aluminium chlorhydrate (Darbre, 2006b), triclosan (Gee et al, 2008) and cyclosiloxanes (McKim et al, 2001;He et al, 2003)]. …”

An analytical multi-residue approach for the determination of semi-volatile organic pollutants in pine needles

“…Synthetic musk compounds (SMCs), widely incorporated in personal care and household products, are one of the "emerging" candidates. Used in rather high quantities on a daily basis, their bioaccumulative potential [8,9] and endocrine disrupting action [10,11] allied to their LRAT [12] make them a current issue of concern. The implementation of atmospheric monitoring plans is essential to assess the properties and behavior of such contaminants.…”

Simultaneous determination of 24 personal care products in fish muscle and liver tissues using QuEChERS extraction coupled with ultra pressure liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometer analyses

“…2. Among the 24 analytes, the recoveries of total 20,19,19,12, and 18 kinds of compounds were in the range of 70-120 % when d-SPE sets (a), (b), (c), (d), and (e) were used, respectively. Actually, it can be seen that the majority of analytes displayed low standard deviation values (<10 %) when the five d-SPE sets were used.…”

“…Although biocides, synthetic musks, Electronic supplementary material The online version of this article (doi:10.1007/s00216-016-9924-y) contains supplementary material, which is available to authorized users. and benzotriazoles show weak acute toxicity to aquatic organisms, their chronic toxicity and endocrine-disrupting effects cannot be neglected [15,16], such as pathological damage to tissues [17], estrogenic activities [18], and anti-estrogenic effect [19].…”