Combinations of parabens at concentrations measured in human breast tissue can increase proliferation of MCF‐7 human breast cancer cells

Abstract

The alkyl esters of p-hydroxybenzoic acid (parabens), which are used as preservatives in consumer products, possess oestrogenic activity and have been measured in human breast tissue. This has raised concerns for a potential involvement in the development of human breast cancer. In this paper, we have investigated the extent to which proliferation of MCF-7 human breast cancer cells can be increased by exposure to the five parabens either alone or in combination at concentrations as recently measured in 160 human breast tissue samples. Determination of no-observed-effect concentrations (NOEC), lowest-observed-effect concentrations (LOEC), EC50 and EC100 values for stimulation of proliferation of MCF-7 cells by five parabens revealed that 43/160 (27%) of the human breast tissue samples contained at least one paraben at a concentration ≥ LOEC and 64/160 (40%) > NOEC. Proliferation of MCF-7 cells could be increased by combining all five parabens at concentrations down to the 50(th) percentile (median) values measured in the tissues. For the 22 tissue samples taken at the site of ER + PR + primary cancers, 12 contained a sufficient concentration of one or more paraben to stimulate proliferation of MCF-7 cells. This demonstrates that parabens, either alone or in combination, are present in human breast tissue at concentrations sufficient to stimulate the proliferation of MCF-7 cells in vitro, and that functional consequences of the presence of paraben in human breast tissue should be assessed on the basis of all five parabens and not single parabens individually.

How Could Endocrine Disrupters Affect Human Health?

“…Analogous results have been reported for parabens, in that five paraben esters were measured in 158 of 160 human breast tissue samples from women with primary breast cancers, but samples with high levels of one ester did not necessarily have high levels of another ester [29]. Further analysis of functionality showed that levels of parabens were at sufficient concentrations in some of these breast tissue samples to enable adverse cellular responses in vitro, but it was different combinations of esters that enabled the end-point response [57].…”

“…The principle that partial agonist effects can be enhanced over a longer time period has been shown in the case of the estrogen agonist properties of triclosan [56]. Other studies have demonstrated that proliferation of estrogen-responsive human breast cancer cells in culture can be observed with reduced concentrations of parabens if the assay time is lengthened [57]. …”

An Introduction to the Challenges for Risk Assessment of Endocrine Disrupting Chemicals

“…The "somethingfrom-nothing" effect demonstrates clearly that cell culture end points [13][14][15] and biomarkers in animal models [16] can be reached by mixtures of chemicals at concentrations at which each chemical individually would have given no measureable response. Using the case of paraben esters as an example of assessing potential adverse effects on the human breast from comparing measurements of their concentrations in human breast tissue [17] and their concentrations needed for in vitro assays of growth of human breast cancer cells [18], experimental studies showed that some breast tissue samples contain sufficient concentration of one paraben to enable breast cancer cell growth in vitro, but other tissues have sufficient concentration only when all five parabens are mixed [18]. Assessing the effects of parabens on human breast tissue, therefore, must be carried out considering concentrations not of just one, but all five paraben esters [19].…”

Efficacies of Antimicrobial Conservants of Various Nonsterile Medicines for Oral Use

“…These limitations arise because these substances may have allergenic, carcinogenic, and mutagenic properties, thus creating real danger to the human body [3,4]. Manufacturers must demonstrate the safety of antimicrobial conservants at the doses used, justify their use, and guarantee their efficacy.…”

“…The medicines Bronchorus ® and Lasolvan ® , diluted 1:10, had antimicrobial actions, which were eliminated at a dilution of 1:50 against C. albicans and 1:20 against A. brasiliensis. 4. Antimicrobial conservants (methylparaben, propylparaben, sodium benzoate, ethanol, and benzoic acid) in the study medicines satisfied the criteria for assessment of efficacy.…”