BPA is a xenoestrogen, exhibiting estrogen-mimicking, hormone-like properties. Although the effect is very weak, the pervasiveness of BPA-containing materials raises concerns. Since 2008, several governments have investigated its safety, which prompted some retailers to withdraw polycarbonate products.
Bisphenol A is primarily used to make plastics, such as this polycarbonate water bottle.
In 2003, U.S. consumption was 856,000 tons, of which 72% was used to make polycarbonate plastic and 21% for epoxy resins. In the U.S., less than 5% of the BPA produced is used in food contact applications, but remains in the canned food industry and printing applications, such as sales receipts.
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. 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. BPA has also been found to act as an agonist of the GPER (GPR30).
The U.S. Environmental Protection Agency (EPA) also holds the position that BPA is not a health concern. In 2011, Andrew Wadge, the chief scientist of the United Kingdom's Food Standards Agency, commented on a 2011 U.S. study on dietary exposure of adult humans to BPA, saying, "This corroborates other independent studies and adds to the evidence that BPA is rapidly absorbed, detoxified, and eliminated from humans – therefore is not a health concern."
The Endocrine Society said in 2015 that the results of ongoing laboratory research gave grounds for concern about the potential hazards of endocrine-disrupting chemicals – including BPA – in the environment, and that on the basis of the precautionary principle these substances should continue to be assessed and tightly regulated. A 2016 review of the literature said that the potential harms caused by BPA were a topic of scientific debate and that further investigation was a priority because of the association between BPA exposure and adverse human health effects including reproductive and developmental effects and metabolic disease.
In 2010, the U.S. Environmental Protection Agency reported that over one million pounds of BPA are released into the environment annually. BPA can be released into the environment by both pre-consumer and post-consumer leaching. Common routes of introduction from the pre-consumer perspective into the environment are directly from plastics, coat and staining manufacturers, foundries who use BPA in casting sand, or transport of BPA and BPA-containing products. Post-consumer BPA waste comes from effluent discharge from municipal wastewater treatment plants, irrigation pipes used in agriculture, ocean-borne plastic trash, indirect leaching from plastic, paper, and metal waste in landfills, and paper or material recycling companies. Despite a rapid soil and water half-life of 4.5 days, and an air half-life of less than one day, BPA's ubiquity makes it an important pollutant. BPA has a low rate of evaporation from water and soil, which presents issues, despite its biodegradability and low concern for bio-accumulation. BPA has low volatility in the atmosphere and a low vapor pressure between 5.00 and 5.32 Pascals. Aqueous solutions of BPA absorbs at wavelengths greater than 250 nm.
BPA interferes with nitrogen fixation at the roots of leguminous plants associated with the bacterial symbiont Sinorhizobium meliloti. BPA affects soybean seedlings with respect to root growth, nitrate production, ammonium production, and the activities of nitrate reductase and nitrite reductase. At low doses of BPA, the growth of roots were improved, the amount of nitrate in roots increased, the amount of ammonium in roots decreased, and the nitrate and nitrite reductase activities remained unchanged. However, at considerably higher concentrations of BPA, the opposite effects were seen for all but an increase in nitrate concentration and a decrease in nitrite and nitrate reductase activities. Nitrogen is both a plant nutritional substance, but also the basis of growth and development in plants.
A 2005 study conducted in the United States had found that 91–98% of BPA may be removed from water during treatment at municipal water treatment plants. A more detailed explanation of aqueous reactions of BPA can be observed in the Degradation of BPA section below. Nevertheless, a 2009 meta-analysis of BPA in the surface water system showed BPA present in surface water and sediment in the U.S. and Europe. According to Environment Canada in 2011, "BPA can currently be found in municipal wastewater. […]initial assessment shows that at low levels, bisphenol A can harm fish and organisms over time."
BPA affects growth, reproduction, and development in aquatic organisms. Among freshwater organisms, fish appear to be the most sensitive species. Evidence of endocrine-related effects in fish, aquatic invertebrates, amphibians, and reptiles has been reported at environmentally relevant exposure levels lower than those required for acute toxicity. There is a widespread variation in reported values for endocrine-related effects, but many fall in the range of 1μg/L to 1 mg/L.
A 2009 review of the biological impacts of plasticizers on wildlife published by the Royal Society with a focus on aquatic and terrestrial annelids, molluscs, crustaceans, insects, fish and amphibians concluded that BPA affects reproduction in all studied animal groups, impairs development in crustaceans and amphibians and induces genetic aberrations.
BPA exhibits very low acute toxicity as indicated by its LD50 of 4 g/kg (mouse). In those mice, weight gain was reduced and exhibited estrogen-like properties. Reports indicate that it is a minor skin irritator as well, though less so than phenol.
The FDA's National Center for Toxicology Research conducted its own research studies. In rodent studies, the amount of BPA passed from the mother to the unborn offspring after oral administration was found to be insignificant. The BPA administration dose for the rodents was 100-1000 times higher than human exposure.
Concerns about the health effects of BPA have led many manufacturers to replace BPA with substitutes such as bisphenol S (BPS) and diphenyl sulfone. However, health concerns have been raised about these substitutes as well.
In the U.S., plastic packaging is split into seven broad classes for recycling purposes by a Plastic identification code. As of 2014 there are no BPA labeling requirements for plastics in the U.S. "In general, plastics that are marked with Resin Identification Codes 1, 2, 4, 5, and 6 are very unlikely to contain BPA. Some, but not all, plastics that are marked with the Resin Identification Code 7 may be made with BPA." Type 7 is the catch-all "other" class, and some type 7 plastics, such as polycarbonate (sometimes identified with the letters "PC" near the recycling symbol) and epoxy resins, are made from bisphenol A monomer. Type 3 (PVC) may contain bisphenol A as an antioxidant in "flexible PVC" softened by plasticizers, but not rigid PVC such as pipe, window frames, and siding.
In 1934 workers at I.G. Farbenindustrie reported the coupling of BPA and epichlorohydrin. Over the following decade, coatings and resins derived from similar materials were described by workers at the companies of DeTrey Freres in Switzerland and DeVoe and Raynolds in the US. This early work underpinned the development of epoxy resins, which in turn motivated production of BPA. The utilization of BPA further expanded with discoveries at Bayer and General Electric on polycarbonate plastics. These plastics first appeared in 1958, being produced by Mobay and General Electric, and Bayer.
In terms of the endocrine disruption controversy, the British biochemist Edward Charles Dodds tested BPA as an artificial estrogen in the early 1930s. He found BPA to be 1 / 37,000 as effective as 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 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.
Currently in the United States, there are 12 states, in addition to Washington D.C. that have restrictions in place against BPA. These states include California, Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, Nevada, New York, Vermont, Washington, and Wisconsin. Each state's restrictions differ slightly, but all restrict the use of BPA in some way.
The following are some examples of legislation in place in these states:
California - Assembly Bill 1319 (2011) prohibits the manufacture and sale of bottles and cups with BPA at detectable levels above 0.1 parts per billion if these items are meant to be used by children 3 years old or younger. It requires manufacturers to use alternative non-toxic materials that are not categorized as carcinogenic or reproductive toxicants.
Delaware - Senate Bill 70 (2011) prohibits the sale of bottles and cups containing BPA if the items are designed to be used by children 4 years old or younger.
Illinois - Senate Bill 2950 (2011) prohibits the sale of empty containers like bottles or cups designed to store food and beverage for children that contain BPA
Maine - House Bill 330 (2011) helped process BPA to be recognized as a priority chemical under Title 38, §1691, Maine's law on toxic chemicals in products designed to be used by children. BPA was formally designated as a substance that must pass through certain reporting requirements for manufactureres of products that contain BPA, as well as authorize the prohibition of sale of products that are reported to contain BPA.
^Pivnenko, K.; Pedersen, G. A.; Eriksson, E.; Astrup, T. F. (1 October 2015). "Bisphenol A and its structural analogues in household waste paper". Waste Management. 44: 39–47. doi:10.1016/j.wasman.2015.07.017. PMID26194879.
^Egan, Michael (2013). "Sarah A. Vogel. Is It Safe? BPA and the Struggle to Define the Safety of Chemicals". Isis. Berkeley: University of California Press. 105 (1): 254. doi:10.1086/676809. ISSN0021-1753.
^Chapin RE, Adams J, Boekelheide K, Gray LE Jr, Hayward SW, Lees PS, McIntyre BS, Portier KM, Schnorr TM, Selevan SG, Vandenbergh JG, Woskie SR (June 2008). "NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A". Birth Defects Res B Dev Reprod Toxicol. 83 (3): 157–395. doi:10.1002/bdrb.20147. PMID18613034.
^ abcdMatsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y (October 2007). "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma". J. Biochem. 142 (4): 517–24. doi:10.1093/jb/mvm158. PMID17761695.
^Abo, Rudy (September 2016). "Optimized photodegradation of Bisphenol A in water using ZnO, TiO2, and SnO2 and photocatalysts under ultraviolet radiation as a decontamination procedure". Drinking Water Engineering and Science. 9 (2): 27–35. doi:10.5194/dwes-9-27-2016.
^Sun, Hai; Wang, Lihong; Zhou, Qing (January 2013). "Effects of bisphenol A on growth and nitrogen nutrition of roots of soybean seedlings". Environmental Toxicology and Chemistry. 32 (1): 174–180. doi:10.1002/etc.2042. ISSN1552-8618. PMID23109293.
^Drewes, J. E.; Hemming, J.; Ladenburger, S. J.; Schauer, J.; Sonzogni, W. An assessment of endocrine disrupting activity changes during wastewater treatment through the use of bioassays and chemical measurements. Water Environ. Res. 2005, 77, 12–23.
А. Дианина (1891) "О продуктахъ конденсацiи кетоновъ съ фенолами" (On condensation products of ketones with phenols), Журнал Русского физико-химического общества (Journal of the Russian Physical Chemistry Society), 23 : 488-517, 523–546, 601–611; see especially pages 491-493 ("Диметилдифеиолметаиь" (dimethyldiphenolmethane)).
^Dodds E. C.; Lawson W. (1938). "Molecular Structure in Relation to Oestrogenic Activity. Compounds without a Phenanthrene Nucleus". Proceedings of the Royal Society of London B: Biological Sciences. 125 (839): 222–232. Bibcode:1938RSPSB.125..222D. doi:10.1098/rspb.1938.0023.
^Ahmed, R. A. M. (2014). "Effect of Prenatal Exposure to Bisphenol A on the Vagina of Albino Rats: immunohistochemical and ultrastructural study". Folia Morphologica. 73 (4): 399–408. doi:10.5603/FM.2014.0061. PMID25448896.
^Ramos, J.G. (2003). "Bisphenol A induces both transient and permanent histofunctional alterations of the hypothalamic-pituitary-gonadal axis in prenatally exposed male rats". Endocrinology. 144 (7): 3206–3215. doi:10.1210/en.2002-0198. PMID12810577.