In-vitro assays to evaluate estrogenic activity of novel bisphenol-A alternatives

Date
2018
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Publisher
University of Delaware
Abstract
Bisphenol-A (BPA), commonly used in polycarbonate plastics and polystyrene resins, is classified as endocrine disruption chemical (EDC) by the FDA due to its estrogenic activity (EA). The primary source of human exposure to BPA is through diet as BPA can migrate into food and beverages from BPA-containing food contact materials. Over the past twenty years, animal tests and epidemiological studies demonstrated that high-level exposure to BPA is associated with various chronic human diseases. Although the current daily exposure level of BPA is considered to be safe by FDA, public sentiment has turned against the use of the chemical and therefore, a sustainably sourced, and less toxic BPA alternative is desirable for the manufacture of food contact materials. Bisguaiacol molecules are lignin derived monomers that have properties similar to those of BPA and could be used as BPA substitutes. For a novel compound to become a feasible alternative to BPA, a risk assessment must be done to demonstrate reduced lower level of toxicity as well as a lower endocrine disruption potential. In the present study, two sensitive and accurate in-vitro bioassays, human breast cancer cells MCF-7 cell proliferation assay and VM7Luc4E2 transactivation test, were used to quantify the EA of four Bisguaiacol-F (BGF) regioisomer mixtures at ten concentrations (from 10-13 to 10-4 M) and seven lignin-derived monomers at seven concentrations (from 10-12 to 10-6 M). The EA of test compounds was calculated as the relative percentage of the maximum EA of 17-βestradiol (E2) (%RME2). For four BGF compounds, the MCF-7 cell proliferation assay showed that BGF mixtures with higher molar ratios of p,p′-BGF and o,p′-BGF regioisomers exhibited lower EA activity than BPA, while BGF samples containing higher molar ratios of the m,p′-BGF regioisomer had no detectable EA. Similar results were obtained with the VM7Luc4E2 TA tests. These findings demonstrate that BGF mixtures with higher molar concentrations of m,p′-BGF may contribute to BGF having undetectable EA. The findings of two in-vitro assays also showed that the other seven monomers had lower EAs than BPA at the same concentration. The reduced EA of Bisphenol-F (BPF) and six Bisguaiacol monomers compared to that of BPA is potentially due to the absence of two methyl groups between the aromatic rings. Bisguaiacol-P (BGP) with only one guaiacol and one hydroxyphenyl structure had the lowest EA among the seven monomers. These data suggest that lignin-derived Bisguaiacol compounds and BPF are acceptable BPA substitutes with respect to their EAs.
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