Bisphenol A

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Bisphenol A
Names
Preferred IUPAC name
4,4′-(Propane-2,2-diyl)diphenol
Other names
  • BPA
  • Diphenylolpropane
  • p,p-Isopropylidenebisphenol
  • 2,2-Bis(4-hydroxyphenyl)propane
  • 2,2-Di(4-phenylol)propane
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
 100.001.133 Edit this at Wikidata
EC Number
  • 201-245-8
IUPHAR/BPS
KEGG
RTECS number
  • SL6300000
UNII
UN number 2430
  • InChI=1S/C15H16O2/c1-15(2,11-3-7-13(16)8-4-11)12-5-9-14(17)10-6-12/h3-10,16-17H,1-2H3 checkY
    Key: IISBACLAFKSPIT-UHFFFAOYSA-N checkY
  • InChI=1/C15H16O2/c1-15(2,11-3-7-13(16)8-4-11)12-5-9-14(17)10-6-12/h3-10,16-17H,1-2H3
    Key: IISBACLAFKSPIT-UHFFFAOYAI
  • Oc1ccc(cc1)C(c2ccc(O)cc2)(C)C
  • CC(C)(c1ccc(cc1)O)c2ccc(cc2)O
Properties
C15H16O2
Molar mass 228.291 g·mol−1
Appearance White solid
Odor Phenolic, medical
Density 1.217 g/cm3[1]
Melting point 155 °C (311 °F; 428 K)[5]
Boiling point 250–252 °C (482–486 °F; 523–525 K)[5] at 13 torrs (0.017 atm)
0.3 g/L (25 °C)[2]
log P 3.41[3]
Vapor pressure 5×10−6 Pa (25 °C)[4]
Hazards[6]
GHS labelling:
GHS05: CorrosiveGHS07: Exclamation markGHS08: Health hazardGHS09: Environmental hazard
Danger
H317, H318, H335, H360, H411[6]
P201, P202, P261, P273, P302+P352, P304+P340, P305+P351+P338, P308+P313, P333+P313, P363, P403+P233[6]
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Flash point 227 °C (441 °F; 500 K)[6]
510 °C (950 °F; 783 K)[6]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Bisphenol A (BPA) is a chemical compound primarily used in the manufacturing of various plastics. It is a colourless solid which is soluble in most common organic solvents, but has very poor solubility in water.[2][7] BPA is produced on an industrial scale by the condensation reaction of phenol and acetone. Global production in 2022 was estimated to be in the region of 10 million tonnes.[8]

BPA's largest single application is as a

PVC, polyurethane, thermal paper, and several other materials. It is not a plasticizer,[11]
although it is often wrongly labelled as such.

The health effects of BPA have been the subject of prolonged public and scientific debate.

food cans,[18] clothing designs,[19] shop receipts,[20] and dental fillings.[21] BPA has been investigated by public health agencies in many countries, as well as by the World Health Organization.[12] 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.[22] 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.[23][24][25]

History

Bisphenol A was first reported in 1891 by the Russian chemist Aleksandr Dianin.[26]

In 1934, workers at

epoxy resins, which in turn motivated production of BPA.[27] 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, General Electric, and Bayer.[28]

The British biochemist Edward

estrogen receptors tens of thousands of times more weakly than estradiol, the major natural female sex hormone.[32][16] 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.[29] BPA was never used as a drug.[29]

Production

The synthesis of BPA still follows Dianin's general method, with the fundamentals changing little in 130 years. The

catalyzed by a strong acid, such as concentrated hydrochloric acid, sulfuric acid, or a solid acid resin such as the sulfonic acid form of polystyrene sulfonate.[34] An excess of phenol is used to ensure full condensation and to limit the formation of byproducts, such as Dianin's compound. BPA is fairly cheap to produce, as the synthesis benefits from a high atom economy and large amounts of both starting materials are available from the cumene process.[7] As the only by-product is water, it may be considered an industrial example of green chemistry. Global production in 2022 was estimated to be in the region of 10 million tonnes.[8]

Synthesis of bisphenol A from phenol and acetone

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.[35] These are not always removed and are known impurities in commercial samples of BPA.[36][35]

Properties

BPA has a fairly high melting point but can be easily dissolved in a broad range of organic solvents including

Spectroscopic data is available from AIST.[42]

Uses and applications

Bisphenol A is primarily used to make plastics, such as this polycarbonate water bottle.

Main uses

Polycarbonates

Main article: Polycarbonate

About 65–70% of all bisphenol A is used to make

Polymerisation is achieved by a reaction with phosgene, conducted under biphasic conditions; the hydrochloric acid is scavenged with aqueous base.[43]
This process converts the individual molecules of BPA into large polymer chains, effectively trapping them.

Epoxy and vinyl ester resins

About 25–30% of all BPA is used in the manufacture of

epoxy resins and vinyl ester resins.[9][10] For epoxy resin, it is first converted to its diglycidyl ether (usually abbreviated BADGE or DGEBA).[44][45] This is achieved by a reaction with epichlorohydrin
under basic conditions.

Some of this is further reacted with

ethoxylated and then converted to its diacrylate and dimethacrylate derivatives (bis-EMA, or EBPADMA). These may be incorporated at low levels in vinyl ester resins to change their physical properties[46] and see common use in dental composites and sealants.[47][48]

Minor uses

The remaining 5% of BPA is used in a wide range of applications, many of which involve plastic.[49] 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.

Plastics

As a major component
As a minor component

Other applications

BPA substitutes

See also: Bisphenol

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.[7] Thus, in bisphenol F, the F signifies formaldehyde. Health concerns have also been raised about these substitutes.[66][24] Alternative polymers, such as tritan copolyester have been developed to give the same properties as polycarbonate (durable, clear) without using BPA or its analogues.

Structural formula Name
CAS
Reactants
Bisphenol AF Bisphenol AF 1478-61-1 Phenol Hexafluoroacetone
Bisphenol F Bisphenol F 620-92-8 Phenol Formaldehyde
Bisphenol S Bisphenol S 80-09-1 Phenol Sulfur trioxide
Bisphenol Z Bisphenol Z 843-55-0 Phenol Cyclohexanone
Tetramethyl bisphenol F 5384-21-4
2,6-xylenol
 Formaldehyde

Human safety

Exposure

The largest exposure humans have had to BPA is from food packaging, particularly the epoxy lining of metal food, beverage cans and plastic bottles.

As a result of the presence of BPA in plastics and other commonplace materials, most people are frequently exposed to trace levels of BPA.

toxicokinetic studies showing the biological half-life of BPA in adult humans to be around two hours.[71][72] 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.[22][17][73] Food and drink containers made from Bisphenol A-containing plastics do not contaminate the content to cause any increased cancer risk.[74]

Health effects and regulation

Main article: Health effects of Bisphenol A

The health effects of BPA have been the subject of prolonged public and scientific debate,[12][13][14] with PubMed listing more than 18,000 scientific papers as of 2024.[75] Concern is mostly related to its estrogen-like activity, although it can interact with other receptor systems as an endocrine-disrupting chemical.[76] 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.[12] A common criticism is that industry-sponsored trials tend to show BPA as being safer than studies performed by academic or government laboratories,[14][77] although this has also been explained in terms of industry studies being better designed.[13][78]

Public health agencies in the EU,

WHO[12] 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,[86] leading to bans on the use of BPA in baby bottles and related products by the US,[87] Canada,[88] and EU[89] 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.[22] 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.[90][91]
In June 2023 after the EFSA reported about the toxicity of BPA the European Union has passed the resolution in early 2024 to ban BPA in all the food contact material including plastic and coated packaging and it said it would also address other bisphenols to avoid replacing with other harmful substances.

BPA exhibits very low

LD50 of 4 g/kg (mouse). Reports indicate that it is a minor skin irritant as well, although less so than phenol.[7]

Pharmacology

Overlay of estradiol, the major female sex hormone in humans (green) and BPA (purple). This displays the structure–activity relationship which allows BPA to mimic the effects of estradiol and other estrogens.

BPA has been found to interact with a diverse range of

LH receptor-ligand binding.[92]

Bisphenol A's interacts with the

4-hydroxytamoxifen (afimoxifene).[93] This may be the mechanism by which BPA acts as a xenoestrogen.[93] 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).[94]

Environmental safety

Distribution and degradation

BPA has been detectable in the natural environment since the 1990s and is now widely distributed.[95] It is primarily a river pollutant,[96] but has also been observed in the marine environment,[97] in soils,[98] and lower levels can also be detected in air.[99] The solubility of BPA in water is low (~300 g per ton of water)[2] but this is still sufficient to make it a significant means of distribution into the environment.[98] 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,[9][100] leaching from PVC items may also be a significant source,[96] as can landfill leachate.[101]

In all cases, wastewater treatment can be highly effective at removing BPA, giving reductions of 91–98%.[102] 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.[103]

Once in the environment BPA is aerobically biodegraded by a wide a variety of organisms.

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.[106]

Environmental effects

BPA is an environmental

bioaccumulating character, the continuous release of BPA into the environment causes continuous exposure to both plant[107] 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.[108] As such, the precise effects of BPA on the growth, reproduction, and development of aquatic organism are not fully understood.[108] Regardless, the existing data shows the effects of BPA on wildlife to be generally negative.[109][110] BPA appears able to affect development and reproduction in a wide range of wildlife,[110] with certain species being particularly sensitive, such as invertebrates and amphibians.[109]

See also

Structurally related
Others

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