Methoxy groups reduced the estrogenic activity of lignin-derivable replacements relative to bisphenol A and bisphenol F as studied through two in vitro assays.

Bisguaiacols are promising lignin-derivable alternatives to bisphenol A (BPA), but limited bioassay data are available on their estrogenic activity (EA). Herein, we investigated the estrogen receptor alpha (ERα)-mediated EA of six newly synthesized bisguaiacols, which differed in the number and location of methoxy substituents, through in vitro assays: MCF-7 cell proliferation and VM7Luc4E2 transactivation. The six bisguaiacols had undetectable EA at concentrations less than 10-7 M, most importantly, with significantly lower EA than BPA over an environmentally relevant range of 10-10-10-7 M. Adding a single methoxy group led to significant reduction in EA in all cases, relative to BPA and one petroleum-derived BPA analogue (bisphenol F, BPF), and the incorporation of more methoxy groups had subtler, but pronounced, impacts on either ERα binding or MCF-7 cell proliferation. In short, the six lignin-inspired bisguaiacols presented herein are viewed as promising sustainable alternatives to BPA and BPF.

Evaluation of Estrogenic Activity of Novel Bisphenol A Alternatives, Four Bioinspired Bisguaiacol F Specimens, by in Vitro Assays.

Alternatives to bisphenol A (BPA), such as lignin-inspired bisguaiacol F (BGF), are of interest for food contact materials due to increasing evidence of estrogenic activity (EA) and exposure-correlated harmful effects of BPA and its analogues. BGF has similar thermal and mechanical properties to BPA, but contains additional methoxy substituents that may significantly reduce its endocrine disruption potential. In this study, the EA of four BGF samples with different regioisomer ratios was quantified relative to 17ß-estradiol at ten concentrations by using two in vitro assays: MCF-7 cell proliferation and VM7Luc4E2 transactivation (TA). The results suggest BGF mixtures with higher molar ratios of p, p'-BGF and o, p'-BGF regioisomers exhibited lower EA than BPA, while BGF samples containing higher molar ratios of m, p'-BGF had no detectable EA over a wide range of test concentrations. These findings suggest the potential of BGF as a viable alternative to BPA for use in more environmentally friendly materials.