Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice

Nat Commun. 2017 Mar 1:8:14585. doi: 10.1038/ncomms14585.


Bisphenol A (BPA) is used in the production of plastic but has oestrogenic activity. Therefore, BPA substitutes, such as fluorene-9-bisphenol (BHPF), have been introduced for the production of so-called 'BPA-free' plastics. Here we show that BHPF is released from commercial 'BPA-free' plastic bottles into drinking water and has anti-oestrogenic effects in mice. We demonstrate that BHPF has anti-oestrogenic activity in vitro and, in an uterotrophic assay in mice, induces low uterine weight, atrophic endometria and causes adverse pregnancy outcomes, even at doses lower than those of BPA for which no observed adverse effect have been reported. Female mice given water containing BHPF released from plastic bottles, have detectable levels of BHPF in serum, low uterine weights and show decreased expressions of oestrogen-responsive genes. We also detect BHPF in the plasma of 7/100 individuals, who regularly drink water from plastic bottles. Our data suggest that BPA substitutes should be tested for anti-oestrogenic activity and call for further study of the toxicological effects of BHPF on human health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / chemistry
  • Benzhydryl Compounds / toxicity*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Catalytic Domain
  • Environmental Exposure / analysis
  • Estradiol / pharmacology
  • Estrogen Antagonists / blood
  • Estrogen Antagonists / chemistry
  • Estrogen Antagonists / toxicity*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Fluorenes / blood
  • Fluorenes / chemistry
  • Fluorenes / toxicity*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Healthy Volunteers
  • Humans
  • MCF-7 Cells
  • Mice
  • Molecular Docking Simulation
  • Phenols / blood
  • Phenols / chemistry
  • Phenols / toxicity*
  • Plastics
  • Pregnancy
  • Pregnancy Outcome*
  • Proton Magnetic Resonance Spectroscopy
  • Reproduction / drug effects
  • Students
  • Toxicity Tests, Chronic


  • Benzhydryl Compounds
  • Estrogen Antagonists
  • Estrogen Receptor alpha
  • Fluorenes
  • Phenols
  • Plastics
  • fluorene
  • Estradiol
  • bisphenol A