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  • Title: An in vitro investigation of endocrine disrupting potentials of ten bisphenol analogues.
    Author: Lin J, Deng L, Sun M, Wang Y, Lee S, Choi K, Liu X.
    Journal: Steroids; 2021 May; 169():108826. PubMed ID: 33753083.
    Abstract:
    The endocrine disruption potency of BPA was reported elsewhere, but the mechanisms of its analogues have not been fully resolved. In this study, endocrine disruption potentials of nine alternative bisphenol analogues, namely 2,2-bis(4-hydroxyphenyl)butane (BPB), 2,2-Bis(4-hydroxy-3-methylphenyl)propane (BPC), 4,4'-dihydroxydiphenylmethane (BPF), 4,4'-(1,3-Phenylene diisopropylidene)bisphenol (BPM), 4,4'-(1,4-phenylenediisopropylidene)bisphenol (BPP), 4,4'- sulfonyldiphenol (BPS), 4,4' cyclohexylidenebisphenol (BPZ), 4,4' (hexafluoroisopropylidene)-diphenol (BPAF) and 4,4'-(1-phenylethylidene)bisphenol (BPAP), plus 2,2-bis(4-hydroxyphenyl)propane (BPA) were investigated by H295R cell and MVLN cell bioassays. In the H295R cell assay, the endpoints included hormone production and key genes for steroidogenesis (CYP11A, CYP17, CYP19 and 3βHSD2) or metabolism sulfotransferase (SULT1A1, SULT2A1 and SULT2B1) at the molecular level. The results indicated that except for BPP or BPAF, the eight other bisphenols significantly increased the E2/T ratio. In addition, BPB, BPF and BPS significantly up-regulate CYP19 gene expression, and only BPB significantly reduced sulfotransferase gene expression. In the MVLN luciferase gene reporter assay, seven bisphenols induced luciferase activity alone, and are 104 to 108-fold less potent than E2. Their nuclear ERα binding activity is in the order of BPAF > BPZ > BPP > BPB > BPA > BPF > BPS. In summary, all nine tested bisphenols showed endocrine toxicity through different mechanisms. Some had similar potency as BPA, but some had even higher potency. Further research is necessary to evaluate the toxicity of these potential BPA substitutes.
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