History of BPA
Bisphenol A was discovered in 1891 by Russian chemist Aleksandr Dianin.
Based on research by chemists at Bayer and General Electric, BPA has been used since the 1950s to harden polycarbonate plastics, and make epoxy resin, which is contained in the lining of food and beverage containers.
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 derive 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 oestrogenic activities, thus it is also considered an endocrine disrupter (ED) and oestrogenic 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.
BPA has been found to bind to both of the nuclear estrogen receptors (ERs), ERα and ERβ. It is 1000- to 2000-fold less potent than estradiol.The drug can both mimic the action of estrogen and antagonize estrogen, indicating that it is a selective estrogen receptor modulator (SERM) orpartial agonist of the ER. At high concentrations, BPA also binds to and acts as an antagonist of the androgen receptor (AR). In addition to receptor binding, the compound has been found to affect Leydig cell steroidogenesis, including affecting 17α-hydroxylase/17,20 lyase andaromatase expression and interfering with LH receptor-ligand binding.
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 US public health regulatory history andChemical manufacturers reactions to bans. As of 2014, research and debates are ongoing as to whether BPA should be banned or not.
ERR-γ (modeled here) has been found in high concentration in theplacenta, explaining reports of high bisphenol accumulation in this tissue.
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 axenoestrogen. 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).
Based on research by chemists at Bayer and General Electric, BPA has been used since the 1950s to harden polycarbonate plastics, and make epoxy resin, which is contained in the lining of food and beverage containers.
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 derive 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 oestrogenic activities, thus it is also considered an endocrine disrupter (ED) and oestrogenic 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.
BPA has been found to bind to both of the nuclear estrogen receptors (ERs), ERα and ERβ. It is 1000- to 2000-fold less potent than estradiol.The drug can both mimic the action of estrogen and antagonize estrogen, indicating that it is a selective estrogen receptor modulator (SERM) orpartial agonist of the ER. At high concentrations, BPA also binds to and acts as an antagonist of the androgen receptor (AR). In addition to receptor binding, the compound has been found to affect Leydig cell steroidogenesis, including affecting 17α-hydroxylase/17,20 lyase andaromatase expression and interfering with LH receptor-ligand binding.
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 US public health regulatory history andChemical manufacturers reactions to bans. As of 2014, research and debates are ongoing as to whether BPA should be banned or not.
ERR-γ (modeled here) has been found in high concentration in theplacenta, explaining reports of high bisphenol accumulation in this tissue.
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 axenoestrogen. 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).