The health effects of BPA have been the subject of prolonged public and scientific debate. BPA is a xenoestrogen, exhibiting hormone-like properties that mimic the effects of estrogen in the body. Although the effect is very weak, the pervasiveness of BPA-containing materials raises concerns, as exposure is effectively lifelong. Many BPA-containing materials are non-obvious but commonly encountered, and include coatings for the inside of food cans, clothing designs, shop receipts, and dental fillings. BPA has been investigated by public health agencies in many countries, as well as by the World Health Organization. While normal exposure is below the level currently associated with risk, several jurisdictions have taken steps to reduce exposure on a precautionary basis, in particular by banning BPA from baby bottles. There is some evidence that BPA exposure in infants has decreased as a result of this. BPA-free plastics have also been introduced, which are manufactured using alternative bisphenols such as bisphenol S and bisphenol F, but there is also controversy around whether these are actually safer.
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 polycarbonateplastics. These plastics first appeared in 1958, being produced by Mobay, 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. Subsequent work found that it bound to estrogen receptors tens of thousands of times more weakly than estradiol, the major natural female sex hormone. 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.
Usually, the addition of acetone takes place at the para position on both phenols, however minor amounts of the ortho-para (up to 3%) and ortho-ortho isomers are also produced, along with several other minor by‑products. These are not always removed and are known impurities in commercial samples of BPA.
About 65–70% of all bisphenol A is used to make polycarbonate plastics, which can consist of nearly 90% BPA by mass. Polymerisation is achieved by a reaction with phosgene, conducted under biphasic conditions; the hydrochloric acid is scavenged with aqueous base. This process converts the individual molecules of BPA into large polymer chains, effectively trapping them.
The remaining 5% of BPA is used in a wide range of applications, many of which involve plastic. BPA is a main component of several high-performance plastics, the production of these is low compared to other plastics but still equals several thousand tons a year. Comparatively minor amounts of BPA are also used as additives or modifiers in some commodity plastics. These materials are much more common but their BPA content will be low.
Polyetherimides such as Ultem can be produced from BPA via a nitro-displacement of appropriate bisnitroimides. These thermoplasticpolyimide plastics have exceptional resistance to mechanical, thermal and chemical damage. They are used in medical devices and other high performance instrumentation.
PVC can contain BPA and its derivatives through multiple routes. BPA is sometimes used as an antioxidant in phthalates, which are extensively used as plasticizers for PVC. BPA has also been used as an antioxidant to protect sensitive PVC heat stabilizers. Historically 5–10% by weight of BPA was included in barium-cadmium types, although these have largely been phased out due health concerns surrounding the cadmium. BPA diglycidyl ether (BADGE) is used as an acid scavenger, particularly in PVC dispersions, such as organosols or plastisols, which are used as coatings for the inside of food cans, as well as embossed clothes designs produced using heat transfer vinyl or screen printing machines.
BPA is used to form a number of flame retardants used in plastics. Bromination of BPA forms tetrabromobisphenol A (TBBPA), which is mainly used as a reactive component of polymers, meaning that it is incorporated into the polymer backbone. It is used to prepare fire-resistant polycarbonates by replacing some bisphenol A. A lower grade of TBBPA is used to prepare epoxy resins, used in printed circuit boards. TBBPA is also converted to tetrabromobisphenol-A-bis(2,3,-dibromopropyl ether) (TBBPA-BDBPE) which can be used as a flame retardant in polypropylene. TBBPA-BDBPE is not chemically bonded to the polymer and can leach out into the environment. The use of these compounds is diminishing due to restrictions on brominated flame retardants. The reaction of BPA with phosphorus oxychloride and phenol forms bisphenol A diphenyl phosphate (BADP), which is used as a liquid flame retarder in some high performance polymer blends such as polycarbonate/ABS mixtures.
BPA is used as an antioxidant in several fields, particularly in brake fluids.
BPA is used as a developing agent in thermal paper (shop receipts). Recycled paper products can also contain BPA, although this can depend strongly on how it is recycled. Deinking can remove 95% of BPA, with the pulp produced used to make newsprint, toilet paper and facial tissues. If deinking is not performed then the BPA remains in the fibers, paper recycled this way is usually made into corrugated fiberboard.
Concerns about the health effects of BPA have led some manufacturers replacing it with other bisphenols, such as bisphenol S and bisphenol F. These are produced in a similar manner to BPA, by replacing acetone with other ketones, which undergo analogous condensation reactions. Thus, in bisphenol F, the F signifies formaldehyde.
Health concerns have also been raised about these substitutes. Alternative polymers, such as tritan copolyester have been developed to give the same properties as polycarbonate (durable, clear) without using BPA or its analogues.
As a result of the presence of BPA in plastics and other commonplace materials, most people are frequently exposed to trace levels of BPA. The primary source of human exposure is via food, as epoxy and PVC are used to line the inside of food cans to prevent corrosion of the metal by acidic foodstuffs. Polycarbonate drinks containers are also a source of exposure, although most disposable drinks bottles are actually made of PET, which contains no BPA. Among the non-food sources, exposures routes include through dust, thermal paper, clothing, dental materials, and medical devices. Although BPA exposure is common it does not accumulate within the body, with toxicokinetic studies showing the biological half-life of BPA in adult humans to be around two hours. The body first converts it into more water-soluble compounds via glucuronidation or sulfation, which are then removed from the body through the urine. This allows exposure to be easily determined by urine testing, facilitating convenient biomonitoring of populations.
The health effects of BPA have been the subject of prolonged public and scientific debate, with PubMed listing more than 17,000 scientific papers as of 2023. Concern is mostly related to its estrogen-like activity, although it can interact with other receptor systems as an endocrine-disrupting chemical. These interactions are all very weak, but exposure to BPA is effectively lifelong, leading to concern over possible cumulative effects. Studying this sort of long‑term, low‑dose interaction is difficult, and although there have been numerous studies, there are considerable discrepancies in their conclusions regarding the nature of the effects observed as well as the levels at which they occur. A common criticism is that industry-sponsored trials tend to show BPA as being safer than studies performed by academic or government laboratories, although this has also been explained in terms of industry studies being better designed.
Public health agencies in the EU, US, Canada, Australia and Japan as well as the WHO have all reviewed the health risks of BPA, and found normal exposure to be below the level currently associated with risk. Regardless, due to the scientific uncertainty, many jurisdictions have taken steps to reduce exposure on a precautionary basis. In particular, infants are considered to be at greater risk, leading to bans on the use of BPA in baby bottles and related products by the US, Canada, and EU amongst others. Bottle producers have largely switched from polycarbonate to polypropylene and there is some evidence that BPA exposure in infants has decreased as a result of this. The European Chemicals Agency has added BPA to the Candidate List of substances of very high concern (SVHC), which would make it easier to restrict or ban its use in future.
BPA exhibits very low acute toxicity as indicated by its LD50 of 4 g/kg (mouse). Reports indicate that it is a minor skin irritant as well, although less so than phenol.
Bisphenol A's interacts with the 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).
Distribution and degradation
BPA has been detectable in the natural environment since the 1990s and is now widely distributed. It is primarily a river pollutant, but has also been observed in the marine environment, in soils, and lower levels can also be detected in air. The solubility of BPA in water is low (~300 g/ton of water) but this is still sufficient to make it a significant means of distribution into the environment. Many of the largest sources of BPA pollution are water-based, particularly wastewater from industrial facilities using BPA.
Paper recycling can be a major source of release when this includes thermal paper,leaching from PVC items may also be a significant source, as can landfill leachate.
In all cases, wastewater treatment can be highly effective at removing BPA, giving reductions of 91–98%. Regardless, the remaining 2–9% of BPA will continue through to the environment, with low levels of BPA commonly observed in surface water and sediment in the U.S. and Europe.
Once in the environment BPA is aerobically biodegraded by a wide a variety of organisms. Its half life in water has been estimated at between 4.5 and 15 days, degradation in the air is faster than this, while soil samples degrade more slowly. BPA in sediment degrades most slowly of all, particularly where this is anaerobic. Abiotic degradation has been reported, but is generally slower than biodegradation. Pathways include photo-oxidation, or reactions with minerals such as goethite which may be present in soils and sediments.
BPA is an environmental contaminant of emerging concern. Despite its short half-life and non-bioaccumulating character, the continuous release of BPA into the environment causes continuous exposure to both plant and animal life. Although many studies have been performed, these often focus on a limited range of model organisms and can use BPA concentrations well beyond environmental levels. As such, the precise effects of BPA on the growth, reproduction, and development of aquatic organism is not fully understood. Regardless, the existing data shows the effects of BPA on wildlife to be generally negative. BPA appears able to affect development and reproduction in a wide range of wildlife, with certain species being particularly sensitive, such as invertebrates and amphibians.
4-tert-Butylphenol - used as a chain-length regulator in the production of polycarbonates and epoxy resins, it has also been studied as a potential endocrine disruptor
^Lim, Caitlin F.; Tanski, Joseph M. (3 August 2007). "Structural Analysis of Bisphenol-A and its Methylene, Sulfur, and Oxygen Bridged Bisphenol Analogs". Journal of Chemical Crystallography. 37 (9): 587–595. doi:10.1007/s10870-007-9207-8. S2CID97284173.
^ abcShareef, Ali; Angove, Michael J.; Wells, John D.; Johnson, Bruce B. (11 May 2006). "Aqueous Solubilities of Estrone, 17β-Estradiol, 17α-Ethynylestradiol, and Bisphenol A". Journal of Chemical & Engineering Data. 51 (3): 879–881. doi:10.1021/je050318c.
^Robinson, Brian J.; Hui, Joseph P.M.; Soo, Evelyn C.; Hellou, Jocelyne (2009). "Estrogenic Compounds in Seawater and Sediment from Halifax Harbour, Nova Scotia, Canada". Environmental Toxicology and Chemistry. 28 (1): 18–25. doi:10.1897/08-203.1. PMID18702564. S2CID13528747.
^ abMitrofanova, S. E.; Bakirova, I. N.; Zenitova, L. A.; Galimzyanova, A. R.; Nefed’ev, E. S. (September 2009). "Polyurethane varnish materials based on diphenylolpropane". Russian Journal of Applied Chemistry. 82 (9): 1630–1635. doi:10.1134/S1070427209090225. S2CID98036316.
^ abcdefgEuropean Commission. Joint Research Centre. Institute for Health Consumer Protection (2010). Updated European Union risk assessment report : 4,4'-isopropylidenediphenol (bisphenol-A) : environment addendum of February 2008. Publications Office. p. 6. doi:10.2788/40195. ISBN9789279175411.
^ abcGeens T, Aerts D, Berthot C, Bourguignon JP, Goeyens L, Lecomte P, et al. (October 2012). "A review of dietary and non-dietary exposure to bisphenol-A". Food and Chemical Toxicology. 50 (10): 3725–3740. doi:10.1016/j.fct.2012.07.059. PMID22889897.
^Noonan GO, Ackerman LK, Begley TH (July 2011). "Concentration of bisphenol A in highly consumed canned foods on the U.S. market". Journal of Agricultural and Food Chemistry. 59 (13): 7178–7185. doi:10.1021/jf201076f. PMID21598963.
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 ("Диметилдифенолметань" (dimethyldiphenolmethane)).
^De Angelis A, Ingallina P, Perego C (March 2004). "Solid Acid Catalysts for Industrial Condensations of Ketones and Aldehydes with Aromatics". Industrial & Engineering Chemistry Research. 43 (5): 1169–1178. doi:10.1021/ie030429+.
^Wolak, J. E.; Knutson, J.; Martin, J. D.; Boyle, P.; Sargent, Andrew L.; White, Jeffery L. (1 December 2003). "Dynamic Disorder and Conformer Exchange in the Crystalline Monomer of Polycarbonate". The Journal of Physical Chemistry B. 107 (48): 13293–13299. doi:10.1021/jp036527q.
^Kroschwitz JI (1998). Kirk-Othmer Encyclopedia of Chemical Technology. Vol. 5 (5 ed.). p. 8. ISBN978-0-471-52695-7.
^Gonçalves F, Kawano Y, Pfeifer C, Stansbury JW, Braga RR (August 2009). "Influence of BisGMA, TEGDMA, and BisEMA contents on viscosity, conversion, and flexural strength of experimental resins and composites". European Journal of Oral Sciences. 117 (4): 442–446. doi:10.1111/j.1600-0722.2009.00636.x. PMID19627357.
^Sideridou, I.; Tserki, V.; Papanastasiou, G. (April 2002). "Effect of chemical structure on degree of conversion in light-cured dimethacrylate-based dental resins". Biomaterials. 23 (8): 1819–1829. doi:10.1016/S0142-9612(01)00308-8. PMID11950052.
^Sideridou, Irini D.; Achilias, Dimitris S. (July 2005). "Elution study of unreacted Bis-GMA, TEGDMA, UDMA, and Bis-EMA from light-cured dental resins and resin composites using HPLC". Journal of Biomedical Materials Research Part B: Applied Biomaterials. 74B (1): 617–626. doi:10.1002/jbm.b.30252. PMID15889433.
^ abcdGeens T, Goeyens L, Covaci A (September 2011). "Are potential sources for human exposure to bisphenol-A overlooked?". International Journal of Hygiene and Environmental Health. 214 (5): 339–347. doi:10.1016/j.ijheh.2011.04.005. PMID21570349.
^Hamerton, Ian (1994). Chemistry and technology of cyanate ester resins (1st ed.). London: Blackie Academic & Professional. ISBN978-0-7514-0044-1.
^Takekoshi T, Kochanowski JE, Manello JS, Webber MJ (June 1985). "Polyetherimides. I. Preparation of dianhydrides containing aromatic ether groups". Journal of Polymer Science: Polymer Chemistry Edition. 23 (6): 1759–1769. Bibcode:1985JPoSA..23.1759T. doi:10.1002/pol.1985.170230616.
^Lau, Kreisler S.Y. (2014). "10 - High-Performance Polyimides and High Temperature Resistant Polymers". Handbook of thermoset plastics (3rd ed.). San Diego: William Andrew. pp. 319–323. ISBN978-1-4557-3107-7.
^Laza JM, Veloso A, Vilas JL (10 January 2021). "Tailoring new bisphenol a ethoxylated shape memory polyurethanes". Journal of Applied Polymer Science. 138 (2): 49660. doi:10.1002/app.49660. S2CID224955435.
^Król, Piotr (2008). Linear polyurethanes : synthesis methods, chemical structures, properties and applications. Leiden: VSP. pp. 11–14. ISBN9789004161245.
^Gauthier, Lewis T.; Laurich, Bruce; Hebert, Craig E.; Drake, Christine; Letcher, Robert J. (20 August 2019). "Tetrabromobisphenol-A-Bis(dibromopropyl ether) Flame Retardant in Eggs, Regurgitates, and Feces of Herring Gulls from Multiple North American Great Lakes Locations". Environmental Science & Technology. 53 (16): 9564–9571. Bibcode:2019EnST...53.9564G. doi:10.1021/acs.est.9b02472. PMID31364365. S2CID198998658.
^Pawlowski, Kristin H; Schartel, Bernhard (November 2007). "Flame retardancy mechanisms of triphenyl phosphate, resorcinol bis(diphenyl phosphate) and bisphenol A bis(diphenyl phosphate) in polycarbonate/acrylonitrile–butadiene–styrene blends". Polymer International. 56 (11): 1404–1414. doi:10.1002/pi.2290.
^Lamprea K, Bressy A, Mirande-Bret C, Caupos E, Gromaire MC (August 2018). "Alkylphenol and bisphenol A contamination of urban runoff: an evaluation of the emission potentials of various construction materials and automotive supplies". Environmental Science and Pollution Research International. 25 (22): 21887–21900. doi:10.1007/s11356-018-2272-z. PMID29796891. S2CID44140721.
^Shin BS, Kim CH, Jun YS, Kim DH, Lee BM, Yoon CH, et al. (December 2004). "Physiologically based pharmacokinetics of bisphenol A". Journal of Toxicology and Environmental Health. Part A. 67 (23–24): 1971–1985. doi:10.1080/15287390490514615. PMID15513896. S2CID24467830.
^Teeguarden, Justin G.; Hanson-Drury, Sesha (December 2013). "A systematic review of Bisphenol A "low dose" studies in the context of human exposure: A case for establishing standards for reporting "low-dose" effects of chemicals". Food and Chemical Toxicology. 62: 935–948. doi:10.1016/j.fct.2013.07.007. PMID23867546.
^CLARITY-BPA Research Program (October 2021). NTP Research Report on the Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA): A Compendium of Published Findings. p. 18. doi:10.22427/NTP-RR-18. PMID34910417. S2CID240266384.
^"EUR-Lex - 32011L0008 - EN - EUR-Lex". EUR-Lex. European Union. COMMISSION DIRECTIVE 2011/8/EU of 28 January 2011 amending Directive 2002/72/EC as regards the restriction of use of Bisphenol A in plastic infant feeding bottles
^ abcdMatsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, et al. (October 2007). "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma". Journal of Biochemistry. 142 (4): 517–524. doi:10.1093/jb/mvm158. PMID17761695.
^ abcCousins, I.T.; Staples, C.A.; Kleĉka, G.M.; Mackay, D. (July 2002). "A Multimedia Assessment of the Environmental Fate of Bisphenol A". Human and Ecological Risk Assessment. 8 (5): 1107–1135. doi:10.1080/1080-700291905846. S2CID43509780.
^Drewes JE, Hemming J, Ladenburger SJ, Schauer J, Sonzogni W (2005). "An assessment of endocrine disrupting activity changes during wastewater treatment through the use of bioassays and chemical measurements". Water Environment Research. 77 (1): 12–23. doi:10.2175/106143005x41573. PMID15765931. S2CID12283834.
^Klecka GM, Staples CA, Clark KE, Van der Hoeven N, Thomas DE, Hentges SG (August 2009). "Exposure analysis of bisphenol A in surface water systems in North America and Europe". Environmental Science & Technology. 43 (16): 6145–50. Bibcode:2009EnST...43.6145K. doi:10.1021/es900598e. PMID19746705.
^Zhang, Chi; Li, Yi; Wang, Chao; Niu, Lihua; Cai, Wei (2 January 2016). "Occurrence of endocrine disrupting compounds in aqueous environment and their bacterial degradation: A review". Critical Reviews in Environmental Science and Technology. 46 (1): 1–59. doi:10.1080/10643389.2015.1061881. S2CID94353391.