Oestrogenic activity of benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) in MCF7 human breast cancer cells in vitro

Abstract

Benzyl salicylate, benzyl benzoate and butylphenylmethylpropional (Lilial) are added to bodycare cosmetics used around the human breast. We report here that all three compounds possess oestrogenic activity in assays using the oestrogen-responsive MCF7 human breast cancer cell line. At 3 000 000-fold molar excess, they were able to partially displace [(3)H]oestradiol from recombinant human oestrogen receptors ERalpha and ERbeta, and from cytosolic ER of MCF7 cells. At concentrations in the range of 5 x 10(-5) to 5 x 10(-4 )m, they were able to increase the expression of a stably integrated oestrogen-responsive reporter gene (ERE-CAT) and of the endogenous oestrogen-responsive pS2 gene in MCF7 cells, albeit to a lesser extent than with 10(-8 )m 17beta-oestradiol. They increased the proliferation of oestrogen-dependent MCF7 cells over 7 days, which could be inhibited by the antioestrogen fulvestrant, suggesting an ER-mediated mechanism. Although the extent of stimulation of proliferation over 7 days was lower with these compounds than with 10(-8 )m 17beta-oestradiol, given a longer time period of 35 days the extent of proliferation with 10(-4 )m benzyl salicylate, benzyl benzoate or butylphenylmethylpropional increased to the same magnitude as observed with 10(-8 )m 17beta-oestradiol over 14 days. This demonstrates that benzyl salicylate, benzyl benzoate and butylphenylmethylpropional are further chemical components of cosmetic products which give oestrogenic responses in a human breast cancer cell line in culture. Further research is now needed to investigate whether oestrogenic responses are detectable using in vivo models and the extent to which these compounds might be absorbed through human skin and might enter human breast tissues.

Fragrances as new contaminants in the Venice lagoon

“…Consequently, the concentrations of Benzyl Salicylate presented here (ldl-2400 ng L −1 ) are the highest among those reported in the literature for surface waters: in Spain (nd-79 ng L −1 ) (Negreira et al, 2010), (10-59 ng L − 1 ) (Vila et al, 2016) and Japan ) (Kameda et al, 2011) The maximum values of Salicylates found in our study (2-7 μg L −1 as single compound) are far below the acute ecotoxicity to Daphnia and other species (0.7-10 mg L − 1 ) reported by the RIFM (Belsito et al, 2012). However, even if these substances are not persistent pollutants in the strictest sense, they are persistently emitted in the environment, and we therefore cannot rule out chronic toxicity, also considering their oestrogenic effects or possible synergistic interactions (Charles and Darbre, 2009;Zhang et al, 2012). It is likely that the urban emissions containing FMs and other PCPs contribute to the overall toxicity of the waters and sediments at a level comparable to that of the industrial area (Picone et al, 2016), causing a decline of the plankton communities, if compared to other areas of the lagoon (Bianchi et al, 2003).…”

“…This compound, used among other purposes as sun-blocking agent due to UV-filter properties (Kameda et al, 2011), is included in the EU list of allergenic fragrances (Heisterberg et al, 2011), and it was recently found to have an oestrogenic activity comparable to bisphenol A (BPA) (Zhang et al, 2012). Other authors found that Benzyl Salicylate gives oestrogenic responses in human breast cancer cells, potentially promoting the development of this disease (Charles and Darbre, 2009). The concentrations of Benzyl and Hexyl Salicylates were measured in U.S. and European wastewater treatment plants (WWTPs) (Simonich et al, 2002(Simonich et al, , 2000, where were reported almost quantitative removals (98.7%) of these substances after secondary treatment.…”

Monitoring proliferative activities of hormone-like odorants in human breast cancer cells by gene transcription profiling and electrical impedance spectroscopy

“…A recent study showed up-regulation of a single marker gene by benzylphenylmethylpropional (Lilial, commercially used in perfumes) in MCF7 cells at concentrations similar to those used in our present study (Charles and Darbre 2009;Pick et al, 2009), We provide here initial evidence for extended regulatory activities of synthetic odorants on a set of ERα-dependent genes suggesting potentially broad influences of these compounds on cellular processes. While we have shown that sandalwood odorants modify gene transcription rapidly, reaching amplitudes comparable to those elicited by E2, significantly lower effects were reported for Lilial.…”

“…The mitogenic response of MCF7 cells to estrogenic compounds is considered to be the most sensitive, specific, and biologically relevant hallmark of estrogenic activity (Fang et al, 2000). Influences of chemicals on MCF7 cell proliferation are usually assayed over a time period of 4-6 days, sometimes even up to 14 days (Soto et al, 1995;Charles and Darbre, 2009). This time consuming approach does not allow for rapid screening of a large number of compounds.…”

Smell of autism: Synthetic fragrances and cause for allergies, asthma, cancer and autism

“…Therefore, in 1973 the US lawmakers passed The Federal Fair Packaging and Labelling Act 14 , exempting fragrance makers from declaring the list of ingredients that form part of fragrances created. Therefore, fragrance concealment is not illegal and is often used by the industry to hide from the public the full list of ingredients, including substances that can cause grave health problems, including breast cancer and autism 2,[17][18][19][20] . We have recently provided evidence, obtained from Ames test analysis of foetal brain cell lines, that exposure to femtomolar concentrations of various perfumes leads to mutagenesis and neuromodulations in human foetal brain cells 21 .…”