page_title: Health effects of Bisphenol A
section_title: Biomedical history
hierarchical_section_title: Health effects of Bisphenol A / Biomedical history
caption_attribution_description: English: Structure of the ESRRG protein. Based on PyMOL rendering of PDB 1kv6.
context_page_description: Bisphenol A controversy centers on concerns and debates about the biomedical significance of bisphenol A, which is a precursor to polymers that are used in some consumer products, including some food containers. The concerns began with the hypothesis that BPA is an endocrine disruptor, i.e. it mimics endocrine hormones and thus has the unintended and possibly far-reaching effects on people in physical contact with the chemical.
  Since 2008, several governments have investigated its safety, which prompted some retailers to withdraw polycarbonate products. The U.S. Food and Drug Administration ended its authorization of the use of BPA in baby bottles and infant formula packaging, based on market abandonment, not safety. The European Union and Canada have banned BPA use in baby bottles.
  The U.S. FDA states "BPA is safe at the current levels occurring in foods" based on extensive research, including two more studies issued by the agency in early 2014.
context_section_description: In the early 1930s, the British biochemist Edward Charles Dodds tested BPA as an artificial estrogen, but found it to be 37,000 times less effective than estradiol. Dodds eventually developed a structurally similar compound, diethylstilbestrol (DES), which was used as a synthetic estrogen drug in women and animals until it was banned due to its risk of causing cancer; the ban on use of DES in humans came in 1971 and in animals, in 1979.  BPA was never used as a drug.  BPA's ability to mimic the effects of natural estrogen derives from the similarity of phenol groups on both BPA and estradiol, which enable this synthetic molecule to trigger estrogenic pathways in the body. Typically phenol-containing molecules similar to BPA are known to exert weak estrogenic activities, thus it is also considered an endocrine disrupter (ED) and estrogenic chemical. Xenoestrogens is another category the chemical BPA fits under because of its capability to interrupt the network that regulates the signals which control the reproductive development in humans and animals.
  In 1997, adverse effects of low-dose BPA exposure in laboratory animals were first proposed. Modern studies began finding possible connections to health issues caused by exposure to BPA during pregnancy and during development. See Public health regulatory history in the United States and Chemical manufacturers' reactions to bans. As of 2014, research and debates are ongoing as to whether BPA should be banned or not.
  A 2007 study investigated the interaction between bisphenol A's and estrogen-related receptor γ (ERR-γ). This orphan receptor (endogenous ligand unknown) behaves as a constitutive activator of transcription. BPA seems to bind strongly to ERR-γ (dissociation constant = 5.5 nM), but only weakly to the ER. BPA binding to ERR-γ preserves its basal constitutive activity. It can also protect it from deactivation from the SERM 4-hydroxytamoxifen (afimoxifene). This may be the mechanism by which BPA acts as a xenoestrogen. Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the placenta, explaining reports of high bisphenol accumulation in this tissue. BPA has also been found to act as an agonist of the GPER (GPR30).
caption: ERR-γ (modeled here) has been found in high concentration in the placenta, explaining reports of high bisphenol accumulation in this tissue.[27]
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