Bisphenol A

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Bisphenol A
Bisphenol A
IUPAC name 4,4'-dihydroxy-2,2-diphenylpropane
Other names BPA, 4,4'-(propan-2-ylidene)diphenol,
p, p'-isopropylidenebisphenol,
4,4´-isopropylidenediphenol.
Identifiers
CAS number [80-05-7]
RTECS number SL6300000
SMILES CC(c2ccc(O)cc2)(C)c1ccc(O)cc1
Properties
Molecular formula C15H16O2
Molar mass 228.29 g/mol
Appearance White to light brown flakes or powder
Density 1.20 g/cm³, solid
Melting point

158 to 159 °C (430 K)
Boiling point

220 °C (493 K) / 4 mmHg
Solubility in water 120–300 ppm (at 21.5 °C)
Hazards
NFPA 704
0
3
0
 
R/S statement R: 36, 37, 38, 43 S: 24, 26, 37
Flash point 227 °C, autoignition: 600 °C
Related compounds
Related compounds phenols
Bisphenol S
Except where noted otherwise, data are given for
materials in their standard state
(at 25 °C, 100 kPa)
Infobox disclaimer and references

Bisphenol A, commonly abbreviated as BPA, is an organic compound with two phenol functional groups. It is a difunctional building block of several important polymers and polymer additives. With an annual production of approximately 3 million tonnes, it is a important monomer in the production of polycarbonate.

Suspect of being hazardous to humans already in the 1930s, in 2007 Bisphenol A has become controversial because it mimics estrogen and thus could induce hormonal responses.

Contents

[edit] Synthesis

Bisphenol A was first reported by A.P. Dianin in 1891.[1][2] It is prepared by the condensation of acetone with two equivalents of phenol. The reaction is catalyzed by an acid, such as hydrochloric acid (HCl) or a sulfonated polystyrene resin. Typically, a large excess of phenol is used to ensure full condensation:

(CH3)2CO + 2 C6H5OH → (CH3)2C(C6H4OH)2 + H2O

A large number of ketones undergo analogous condensation reactions. The method is efficient and the only by-product is water.[3]

[edit] Use

Further information: Polycarbonate

Products containing or made from Bisphenol A have been in commerce for more than 50 years, and its current uses are numerous. It is used in the synthesis of polyesters, polysulfones, and polyether ketones, as an antioxidant in some plasticizers, and as a polymerization inhibitor in PVC. It is a key monomer in production of polycarbonate plastic and epoxy resins.[3] Polycarbonate plastic, which is clear and nearly shatter-proof, is used to make a variety of common products including baby and water bottles, sports equipment, medical devices, CDs, and household electronics.[4] Epoxy resins are used as coatings on the inside of almost all food and beverage cans.[5] It is also a precursor to the flame retardant tetrabromobisphenol A, and was formerly used as a fungicide.[6]

Global production of bisphenol A in 2003 was estimated to be about 3 million metric tonnes (t).[7] In the U.S., it is manufactured by Bayer MaterialScience, Dow Chemical Company, General Electric, Hexion Specialty Chemicals, and Sunoco Chemicals. In 2004, these companies produced just over 1 million t of bisphenol A, up from just 7,260 t in 1991. In 2003, annual U.S. consumption was 856,000 t, 72% of which was used to make polycarbonate plastic and 21% going into epoxy resins.[4]

[edit] Health effects

Bisphenol A has a low acute toxicity, with an oral LD50 of 3250 mg/kg in rats.[8] However, bisphenol A is an endocrine disruptor: it is an estrogen receptor agonist,[9] and such agonists can act like the body's own hormones, leading to similar physiological effects on the body.[10] There is thus concern that long term low dose exposure to bisphenol A may induce chronic toxicity in humans.[11][12][13]

[edit] Endocrine disruption

The first evidence of the estrogenicity of bisphenol A came from experiments in the 1930s in which it was fed to ovariectomized rats,[14][15] but it was not until 1997 that adverse effects of low-dose exposure on laboratory animals were first reported.[5] Since then, its endocrine disrupting properties have been extensively investigated, and more than 100 studies have been published "rais[ing] health concerns" about the chemical.[16] Early development appears to be the period of greatest sensitivity to its effects,[17] and studies have demonstrated developmental toxicity, carcinogenic effects, and possible neurotoxicity at low doses in animal models (see table below).[18][19] Recent studies suggest it may also be linked to obesity[20] by triggering fat-cell activity[21] and have confirmed that bisphenol A exposure during development has carcinogenic effects and produce precursors of breast cancer.[22][23] However, neither the U.S. Environmental Protection Agency[24] nor the International Agency for Research on Cancer[25] have evaluated Bisphenol A for possible carcinogenic activity.

In 2007, a consensus statement by 38 experts on bisphenol A concluded that average levels in people are above those that cause harm to animals in laboratory experiments,[26] and a panel convened by the U.S. National Institutes of Health determined that there was "some concern" about BPA's effects on fetal and infant brain development and behavior.[4] A 2008 draft report by the U.S. National Toxicology Program (NTP) agreed with the panel, concluding that "there is some concern for neural and behavioral effects in fetuses, infants, and children at current human exposures," and that there is "some concern for bisphenol A exposure in these populations based on effects in the prostate gland, mammary gland, and an earlier age for puberty in females." The NPT also concluded that there is negligible concern that "exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring" or that it causes adverse effects in exposed adults.[27]

In April 2008, the Health Canada released its Draft Screening Assessment for bisphenol A, which concluded that the chemical may pose some risk to infants[28] and proposed classifying the chemical as "'toxic' to human health and the environment."[29] This action follows Canadian regulators selection of bisphenol A in 2006 as one of 200 substances deserving of thorough safety assessments after preliminary studies had found it to be "inherently toxic"; the chemical had not previously been studied by them in depth, having been accepted under grandfather clauses when stricter regulations were passed in the 1980s.[30]

In contrast to the recent actions in North America, in January 2006 the German Federal Institute for Risk Assessment announced that polycarbonate baby bottles are safe and stated that published research on the health effects of Bisphenol A is "difficult to interpret and [is] occasionally contradictory".[31] An assessment released later that year by the European Union’s Food Safety Authority reached a similar conclusion, expressing "considerable reservations" about the biological significance and robustness of the low-dose exposure studies on rodents.[32] In 2007 Japan also concluded that "the current exposure levels of BPA will not pose any unacceptable risk to human health that a ban is not needed."[33]

Some toxicologists and regulatory agencies have criticized low-dose toxicity studies, especially those that involved injecting bisphenol A directly into animals, since human exposures typically involve ingestion and subsequent metabolization in the liver, and the experimental design of some of these studies has also been questioned.[34][35] Studies have also appeared pointing out flaws in chemical industry funded studies that found no evidence of adverse effects from low dose exposure,[36] and a study from 2008 concluded that blood levels of bisphenol A in neonatal mice are the same whether it is injected or ingested.[37]

[edit] Selected studies on low dose bisphenol A exposure in animals

Dose (µg/kg/day) Effects (measured in studies of mice or rats,
descriptions are from Environmental Working Group)[38][30]		 Study Year
0.025 Permanent changes to genital tract 2005[39]
0.025 Changes in breast tissue that predispose cells to hormones and carcinogens 2005 [40]
2 increased prostate weight 30% 1997[41]
2 lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus. 2002[42]
2.4 Decline in testicular testosterone 2004[43]
2.5 Breast cells predisposed to cancer 2007[44]
10 Prostate cells more sensitive to hormones and cancer 2006[45]
10 Decreased maternal behaviors 2002[46]
30 Reversed the normal sex differences in brain structure and behavior 2003[47]
50 U.S. human exposure limit (not a result from an animal study, but a guideline set by EPA) 1998[48]

[edit] Human exposure to bisphenol A

Bisphenol A has been known to leach from the plastic lining of canned foods [49] and, to a lesser degree, polycarbonate plastics that are cleaned with harsh detergents or used to contain acidic or high-temperature liquids. Studies by the CDC found bisphenol A in the urine of 95% of adults sampled in 1988-1994[50] and in 93% of children and adults tested in 2003-04.[51] Almost all exposure is through diet, and infants fed with liquid formula are among the most exposed. Infants fed canned formula with polycarbonate bottles can consume quantities of bisphenol A up to 13 µg/kg/day (see table below),[52] while the most sensitive animal studies show effects at much lower concentrations. Debate continues on what is the safe limit of this compound. Within the United States, an exposure of up to 50 µg/kg/day (50 ppb/day) is considered safe[30] by the United States Environmental Protection Agency.[53]

Dr. Maida Galvez, a pediatrician studying BPA, recommends parents stay away from bottles containing the chemical and says, "We know the animal studies raise concerns, but there aren't human studies showing effects yet ... so, when we don't have the evidence, what we recommend is that parents try to err on the side of caution."[54]

Population Estimated daily bisphenol A intake, μg/kg/day.
Table adapted from the National Toxicology Program Expert Panel Report.[4]
Infant (0-6 months)
formula-fed
1-11
Infant (0-6 months)
breast-fed
0.2-1
Infant (6-12 months)
1.65-13
Child (1.5-6 years)
0.043-14.7
Adult
0.008-1.5

[edit] Government and industry response

On April 18, 2008 Canadian Health Minister Tony Clement announced that Canada intends to ban the import, sale, and advertising of polycarbonate baby bottles containing bisphenol A over concerns of the safety of bisphenol A. While Health Canada concluded that human exposures are less than the levels deemed to be potentially unsafe, the margin of safety was considered too low for formula-fed infants.[17][55] Around the same time, Wal-Mart announced that it was immediately ceasing sales in all its Canadian stores of food containers, water and baby bottles, sippy cups, and pacifiers containing bisphenol A, and that it would phase out baby bottles made with it in U.S. stores by early 2009.[56] Nalgene also announced it will stop using the chemical in its products,[57] and Toys-R-Us said it too will cease selling baby bottles made from it.[58] Subsequent news reports showed many retailers removing polycarbonate drinking products from their shelves.[59]

As of the release of NTP and Health Canada reports, 10 U.S. states, including California, Maryland,[16] Connecticut[60] and New Jersey,[61] already had legislation pending that would affect the use of BPA, and in the wake of these reports, U.S. Senator Charles Schumer (D–N.Y.) introduced legislation that would ban bisphenol A nationally from products for infants.[16] In addition, the U.S. Congress is investigating the Weinberg Group, a chemical industry consulting firm, for its role in downplaying the health effects of bisphenol A and other chemicals,[62] and the Energy and Commerce Committee in the House of Representatives is investigating its use in baby products as well as the FDA's approval of the chemical. In asking the FDA to reassess its approval of bisphenol A, committee chairman Bart Stupak (D–Mich.) said "We would expect the FDA to make decisions based on the best available science…Yet the FDA relied on only two industry-funded studies, while other respected authorities used all available data to reach vastly different conclusions." While the FDA has set up a task force to address these concerns, it maintains that bisphenol A is safe and is not recommending that people avoid using products made from it. The Consumer Product Safety Commission agrees, and its deputy director has stressed that use of bisphenol A based plastics have many practical benefits, and that "a ban could result in less effective protection of children from head, eye, or bodily injury."[5]

In response to the recent events, an American Chemistry Council (ACC)/BPA Global Group spokesman said, “The weight of scientific evidence, as assessed by Health Canada and other agencies around the world, provides reassurance that consumers can continue to safely use products made from bisphenol A."[63] The ACC says that bisphenol A does not pose a risk to consumers and has called on the Food and Drug Administration to review the chemical. The ACC also called the media coverage of the controversy "unnecessarily confusing and frightening the public."[60] The Grocery Manufacturers Association also insists that bisphenol A is safe, and argues that "Data purporting to demonstrate 'low' dose effects on the male reproductive system by BPA have not been successfully replicated and, therefore, are not credible to estimate human health risks and safety in light of the weight of a large body of evidence to the contrary."[64] A spokesman for the tin can industry has said that without lining cans with bisphenol A based resins, E. coli and botulism poisoning would be "rampant."[5] An industry website Bisphenol-a.org also carries a number of articles dated as recently as February 2008 claiming the use of Polycarbonate water bottles is safe.

The chemical industry has been criticized over bisphenol A by Democrats and their allies. David Michaels, who served in the Clinton Adminstration, told the Washington Post that "Tobacco figured this out, and essentially it's the same model … If you fight the science, you're able to postpone regulation and victim compensation, as well. As in this case, eventually the science becomes overwhelming. But if you can get five or 10 years of avoiding pollution control or production of chemicals, you've greatly increased your product."[16]

In the U.S. retail sector, growing concern over bisphenol A exposure had already led a number of retailers to stop using bisphenol A, particularly chains promoting healthy food and lifestyles. In 2005, Patagonia Inc. ceased selling polycarbonate bottles, and in 2006, Whole Foods Markets ceased selling baby bottles as did Mountain Equipment Co-op in 2007.[65]

The city of San Francisco, California, banned the sale of baby bottles and other products for young children containing bisphenol A effective December 2006, and was, at the time, the only jurisdiction in the world to outright forbid the substance.[66] The ban was never enforced, and in May 2007 the city repealed the ban.

[edit] Environmental risk

As an environmental contaminant this compound interferes with nitrogen fixation at the roots of leguminous plants associated with the bacterial symbiont Sinorhizobium meliloti. Despite a half-life in the soil of only 1–10 days, its ubiquity makes it an important pollutant.[67] According to Health Canada, "initial assessment shows that at low levels, bisphenol A can harm fish and organisms over time. Studies also indicate that it can currently be found in municipal wastewater."[68]

[edit] Identification in plastics

Some type 7 plastics may leach bisphenol A
Some type 7 plastics may leach bisphenol A
Some type 3 plastics may leach bisphenol A
Some type 3 plastics may leach bisphenol A

There are seven classes of plastics used in packaging applications. 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.[3] When such plastics are exposed to hot liquids, bisphenol A leaches out 55 times faster than it does under normal conditions, at up to 32 ng/hour.[69] Type 3 (PVC) can also contain bisphenol A as antioxidant in plasticizers.[3] Types 1 (PET), 2 (HDPE), 4 (LDPE), 5 (polypropylene), and 6 (polystyrene) do not use bisphenol A during polymerization or package forming,[70] and thus will not leach bisphenol A into food or beverages.

[edit] References

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  7. ^ Draft Screening Assessment for The Challenge Phenol, 4,4' -(1-methylethylidene)bis- (Bisphenol A) Chemical Abstracts Service Registry Number 80-05-7, Environment Canada.
  8. ^ MSDS: Bisphenol A 99+%
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  12. ^ Hot liquids release potentially harmful chemicals in polycarbonate plastic bottles
  13. ^ Le HH, Carlson EM, Chua JP, Belcher SM (2008). "Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons". Toxicol. Lett. 176 (2): 149–56. doi:10.1016/j.toxlet.2007.11.001. PMID 18155859. 
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  20. ^ "Bisphenol A linked to obesity in mice, study says", CTV News, 2008-05-15. Retrieved on 2008-05-16. 
  21. ^ Grossman, Elizabeth. (March 12, 2007). "Chemicals May Play Role in Rise in Obesity.". Washington Post.. 
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  35. ^ Weight of the Evidence Evaluation of Low-Dose Reproductive and Developmental Effects of Bisphenol A, George M. Gray, Joshua T. Cohen, Gerald Cunha, Claude Hughes, Ernest E. McConnell, Lorenz Rhomberg, I. Glenn Sipes, and Donald Mattison7Human and Ecological Risk Assessment, 10: 875–921, 2004.
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  38. ^ This table is adapted from: EWG, 2007. "Many studies confirm BPA's low-dose toxicity across a diverse range of toxic effects," Environmental Working Group Report: A Survey of Bisphenol A in U.S. Canned Foods. Accessed November 4th, 2007 at http://www.ewg.org/node/20941. All studies included in this table where judged by the CEHRH panel to be at least of moderate usefulness for assessing the risk of BPA to human reproduction.
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  40. ^ Muñoz-de-Toro M, Markey CM, Wadia PR, et al (2005). "Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice". Endocrinology 146 (9): 4138-47. doi:10.1210/en.2005-0340. PMID 15919749. 
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  42. ^ Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H, Iguchi T (2002). "Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction". Reprod. Toxicol. 16 (2): 117-22. PMID 11955942. 
  43. ^ Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, Hardy MP (2004). "Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells". Endocrinology 145 (2): 592–603. doi:10.1210/en.2003-1174. PMID 14605012. 
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  45. ^ Ho SM, Tang WY, Belmonte de Frausto J, Prins GS (2006). "Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4". Cancer Res. 66 (11): 5624–32. doi:10.1158/0008-5472.CAN-06-0516. PMID 16740699. 
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  53. ^ Bisphenol A - United States Environmental Protection Agency
  54. ^ Parents Concerned Over Potentially Toxic Baby Bottles ABC News, Feb. 7, 2008.
  55. ^ The government has given the public 60 days to comment on the proposed ban starting April 19, 2008 and will evaluate whether the ban will become law in October 2008. "Government of Canada Takes Action on Another Chemical of Concern: Bisphenol A". Retrieved on 2008-04-18. 
  56. ^ Wal-Mart to pull baby bottles made with chemical BPA: Washington Post, Market Watch, April 18, 2008.
  57. ^ Bottle Maker to Stop Using Plastic Linked to Health Concerns, New York Times, April 18, 2008.
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  59. ^ CANOE - CNEWS - Politics: Bisphenol A water-bottle removal expanding among Canadian retailers
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[edit] External links