Estrogenic activity of musk fragrances detected by the E-screen assay using human MCF-7 cells

The widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment (as well as their accumulation in human adipose tissue) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity. A variety of musk fragrances were tested using the E-screen assay. A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks (musk xylene, musk ketone), a major metabolite of musk xylene (p-amino-musk xylene), and the polycyclic musk fragrance AHTN. This indicates that these substances do, in fact, demonstrate estrogenic activity. Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated. It must be noted, however, that the effective estrogenic strength and estrogenic potency were low compared to 17b-estradiol. The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances, a group of substances that have not yet been well characterized in respect to their toxicological properties, has also been shown to be weakly estrogenically active in vitro. E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK, the macrocyclic musk fragrances ethylene brassylate, ethylene dodecandioate, and cyclopentadecanolide, are not estrogenically active.