Bisphenol A
From DrugPedia: A Wikipedia for Drug discovery
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| Bisphenol A
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| Systematic (IUPAC) name | |
| 4-[2-(4-hydroxyphenyl)propan-2-yl]phenol | |
| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | |
| ChemSpider | |
| Chemical data | |
| Formula | C15H16O2 |
| Mol. mass | 228.29 |
| SMILES | & |
| Synonyms | Diphenylolpropane |
| Physical data | |
| Melt. point | 153(EXP) °C |
| Boiling point | 220 °C (493 K) / 4 mmHg °C (Expression error: Unrecognised punctuation character "�" °F) |
| Solubility in water | 120(EXP) at 25oC mg/mL |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Contents |
[edit] Description
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 2–3 million tonnes, it is an important monomer in the production of polycarbonate.
Suspected of being hazardous to humans since the 1930s, concerns about the use of bisphenol A in consumer products grabbed headlines in 2008 when several governments issued reports questioning its safety, and some retailers pulled products made from it off their shelves.
[edit] Synthesis
Bisphenol A was first reported by A.P. Dianin in 1891.<ref name=dianin>Dianin (1891). "Zhurnal russkogo fiziko-khimicheskogo obshchestva" 23: pp. 492–.</ref><ref>Zincke, Theodor (1905). "Ueber die Einwirkung von Brom und von Chlor auf Phenole: Substitutionsprodukte, Pseudobromide und Pseudochloride". Justus Liebigs Annalen der Chemie 343: 75–99. doi:.</ref> It is prepared by the condensation of acetone (hence the suffix A in the name)<ref>Template:Cite book</ref> 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.<ref name=Fiege>Template:Citation</ref>
[edit] Use
Template:Further 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.<ref name=Fiege/> 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 and dental devices, dental composite (white) fillings and sealants, lenses, and household electronics.<ref name="CERHR">Template:Cite news</ref> Polycarbonate is used in the manufacture of all CDs and DVDs. Epoxy resins are used as coatings on the inside of almost all food and beverage cans.<ref name="C&ENews">Erickson, Britt E. (June 2, 2008). "Bisphenol A under scrutiny". Chemical and Engineering News 86 (22): 36–39. American Chemical Society.</ref> Bisphenol A is also a precursor to the flame retardant, tetrabromobisphenol A, and was formerly used as a fungicide.<ref>Pesticideinfo.org: Bisphenol A</ref>
Global production of bisphenol A in 2003 was estimated to be over 2 million metric tonnes (t).<ref name="Lang et al."/> 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.<ref name="CERHR"/>
[edit] Health effects
Bisphenol A has low acute toxicity, with an oral LD50 of 3250 mg/kg in rats,<ref>MSDS: Bisphenol A 99+%</ref> but it is an endocrine disruptor.<ref>Okada H, Tokunaga T, Liu X, Takayanagi S, Matsushima A, Shimohigashi Y (January 2008). "Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma". Environ. Health Perspect. 116 (1): 32–8. doi:. PMID 18197296.</ref><ref name=JAMAVS>vom Saal FS, Myers JP (2008). "Bisphenol A and Risk of Metabolic Disorders". JAMA (300). doi:.</ref> Low doses of bisphenol A can mimic the body's own hormones, possibly causing negative health effects.<ref>O’Connor, Chapin (2003). "Critical evaluation of observed adverse effects of endocrine active substances on reproduction and development, the immune system, and the nervous system" (Full Article). Pure Appl. Chem 75 (11–12): 2099–2123. doi:. Retrieved on 2007-02-28.</cite></ref> There is thus concern that long term low dose exposure to bisphenol A may induce chronic toxicity in humans.<ref><cite style="font-style:normal">vom Saal FS, Hughes C (2005). "An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment". Environ. Health Perspect. 113 (8): 926–33. PMID 16079060.</cite></ref><ref>Hot liquids release potentially harmful chemicals in polycarbonate plastic bottles</ref><ref name=pmid_18155859><cite style="font-style:normal">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:. PMID 18155859.</cite></ref>
[edit] Animal Studies
The first evidence of the estrogenicity of bisphenol A came from experiments in the 1930s in which it was fed to ovariectomized rats,<ref>E. C. Dodds and Wilfrid Lawson, "Synthetic Œstrogenic Agents without the Phenanthrene Nucleus", Nature, 137 (1936), 996.</ref><ref>E. C. Dodds and W. Lawson, Proceedings of the Royal Society of London, Series B, Biological Sciences, 125, #839 (27-IV-1938), pp. 222–232.</ref> but it was not until 1997 that adverse effects of low-dose exposure on laboratory animals were first reported.<ref name=C&ENews/> 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.<ref name="WaPo">Template:Citation.</ref>
Early development appears to be the period of greatest sensitivity to its effects,<ref name=HealthCanada>Draft Screening Assessment for The Challenge Phenol, 4,4' -(1-methylethylidene)bis- (Bisphenol A)Chemical Abstracts Service Registry Number 80-05-7. Health Canada, 2008.</ref> and studies have demonstrated developmental toxicity, carcinogenic effects, and possible neurotoxicity at low doses in animal models (see table below).<ref><cite style="font-style:normal">Lee YM, Seong MJ, Lee JW, et al (March 2007). "Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen". J. Vet. Sci. 8 (1): 27–38. PMID 17322771.</cite></ref><ref><cite style="font-style:normal">Zsarnovszky A, Le HH, Wang HS, Belcher SM. (2005). "Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A". Endocrinology. 146 (12): 5388–96. doi:. PMID 16123166.</cite></ref> Recent studies suggest it may also be linked to obesity<ref>Template:Cite news</ref> by triggering fat-cell activity<ref><cite style="font-style:normal">Grossman, Elizabeth. (March 12, 2007). "Chemicals May Play Role in Rise in Obesity". Washington Post..</cite></ref> and have confirmed that bisphenol A exposure during development has carcinogenic effects and produce precursors of breast cancer.<ref><cite style="font-style:normal">Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM (2007). "Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure". Reprod. Toxicol. 23 (3): 383–90. doi:. PMID 17123778.</cite></ref><ref name=pmid_18226065><cite style="font-style:normal">Soto AM, Vandenberg LN, Maffini MV, Sonnenschein C (2008). "Does breast cancer start in the womb?". Basic Clin. Pharmacol. Toxicol. 102 (2): 125–33. doi:10.1111/j.1742-7843.2007.00165.x (inactive 2008-06-22). PMID 18226065.</cite></ref> However, neither the U.S. Environmental Protection Agency<ref>U.S.EPA, IRIS: Bisphenol A</ref> nor the International Agency for Research on Cancer<ref>AGENTS REVIEWED BY THE IARC MONOGRAPHS Volumes 1–99</ref> have evaluated bisphenol A for possible carcinogenic activity. Most recently, a study by the Yale School of Medicine demonstrated that adverse neurological effects occur in non-human primates regularly exposed to bisphenol A at levels equal to the United States Environmental Protection Agency's (EPA) maximum safe dose of 50 µg/kg/day.<ref name="pmid18768812"><cite style="font-style:normal">Leranth C, Hajszan T, Szigeti-Buck K, Bober J, Maclusky NJ (September 2008). "Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates". Proc. Natl. Acad. Sci. U.S.A.. doi:. PMID 18768812.</cite></ref><ref name="Layton2">Template:Cite news</ref> This research found a connection between BPA and interference with brain cell connections vital to memory, learning and mood.
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,<ref><cite style="font-style:normal">vom Saal FS, Akingbemi BT, Belcher SM, et al (2007). "Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure". Reprod. Toxicol. 24 (2): 131–8. doi:. PMID 17768031.</cite></ref> 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.<ref name="CERHR"/> A 2008 report by the U.S. National Toxicology Program (NTP) agreed with the panel, expressing "some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A," and "minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A." The NTP had "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."<ref name=NTP08>Since you asked - Bisphenol A: Questions and Answers about the Draft National Toxicology Program Brief on Bisphenol A, National Institute of Environmental Health Sciences website.</ref>
In April 2008, Health Canada released its Draft Screening Assessment for bisphenol A, which concluded that the chemical may pose some risk to infants<ref name='C&EN'>Template:Citation.</ref> and proposed classifying the chemical as "'toxic' to human health and the environment."<ref>Government of Canada Takes Action on Another Chemical of Concern: Bisphenol A, Chemical Substances, Health Canada. Accessed April 19, 2008.</ref> This action follows Canadian regulators selection of bisphenol A in 2006 as one of 200 substances deserving of thorough safety assessments because 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.<ref name="globemittelstaedt">Template:Cite news</ref>
In contrast to the recent actions in North America, earlier assessment by governments in other regions found no cause for concern. In January 2006 the German regulators 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".<ref>Selected questions and answers relating to bisphenol A in baby bottles- Federal Institute for Risk Assessment</ref> Also that year 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.<ref>Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to 2,2-BIS(4-HYDROXYPHENYL)PROPANE, European Food Safety Authority, November 29, 2006. Accessed April 19, 2008</ref> In 2007 Japan also concluded that for individuals in that country, "the current exposure levels of BPA will not pose any unacceptable risk to human health [and] that a ban is not needed."<ref>Bisphenol A Risk Assessment Document (AIST Risk Assessment Document Series No. 4) Summary, New Energy and Industrial Technology Development Organization, Research Center for Chemical Risk Management, National Institute of Advanced Industrial Science and Technology, November 2007.</ref>
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 metabolism in the liver, and the experimental design of a few of these early studies has also been questioned.<ref name="pmid16954066"><cite style="font-style:normal">Goodman JE, McConnell EE, Sipes IG, et al (2006). "An updated weight of the evidence evaluation of reproductive and developmental effects of low doses of bisphenol A". Crit. Rev. Toxicol. 36 (5): 387–457. doi:. PMID 16954066.</cite></ref><ref>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.</ref> On the other hand, studies have also appeared pointing out flaws in chemical-industry-funded studies that found no evidence of adverse effects from low dose exposure,<ref><cite style="font-style:normal">vom Saal FS, Welshons WV (January 2006). "Large effects from small exposures. II. The importance of positive controls in low-dose research on bisphenol A". Environ. Res. 100 (1): 50–76. doi:. PMID 16256977.</cite></ref><ref name=JAMAVS/> and a study from 2008 concluded that blood levels of bisphenol A in neonatal mice are the same whether it is injected or ingested.<ref name="pmid18295446"><cite style="font-style:normal">Taylor JA, Welshons WV, Vom Saal FS (February 2008). "No effect of route of exposure (oral; subcutaneous injection) on plasma bisphenol A throughout 24h after administration in neonatal female mice". Reprod. Toxicol. 25 (2): 169–76. doi:. PMID 18295446. Retrieved on 2008-05-05.</cite></ref>
[edit] Selected studies on low dose bisphenol A exposure in animals
| Dose (µg/kg/day) | Effects (measured in studies of mice or rats, descriptions (in quotes) are from Environmental Working Group)<ref name="EWG-BPA">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.</ref><ref name="globemittelstaedt"/> | Study Year |
| 0.025 | "Permanent changes to genital tract" | 2005<ref name="pmid15689538"><cite style="font-style:normal">Markey CM, Wadia PR, Rubin BS, Sonnenschein C, Soto AM (2005). "Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract". Biol. Reprod. 72 (6): 1344–51. doi:. PMID 15689538.</cite></ref> |
| 0.025 | "Changes in breast tissue that predispose cells to hormones and carcinogens" | 2005<ref name="pmid15919749"><cite style="font-style:normal">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:. PMID 15919749.</cite></ref> |
| 2 | "increased prostate weight 30%" | 1997<ref name="pmid9074884"><cite style="font-style:normal">Nagel SC, vom Saal FS, Thayer KA, Dhar MG, Boechler M, Welshons WV (1997). "Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol". Environ. Health Perspect. 105 (1): 70–6. PMID 9074884.</cite></ref> |
| 2 | "lower bodyweight, increase of anogenital distance in both genders, signs of early puberty and longer estrus." | 2002<ref name="pmid11955942"><cite style="font-style:normal">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.</cite></ref> |
| 2.4 | "Decline in testicular testosterone" | 2004<ref name="pmid14605012"><cite style="font-style:normal">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:. PMID 14605012.</cite></ref> |
| 2.5 | "Breast cells predisposed to cancer" | 2007<ref name="pmid17123778"><cite style="font-style:normal">Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM (2007). "Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure". Reprod. Toxicol. 23 (3): 383–90. doi:. PMID 17123778.</cite></ref> |
| 10 | "Prostate cells more sensitive to hormones and cancer" | 2006<ref name="pmid16740699"><cite style="font-style:normal">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:. PMID 16740699.</cite></ref> |
| 10 | "Decreased maternal behaviors" | 2002<ref name="pmid12060838"><cite style="font-style:normal">Palanza PL, Howdeshell KL, Parmigiani S, vom Saal FS (2002). "Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice". Environ. Health Perspect. 110 Suppl 3: 415–22. PMID 12060838.</cite></ref> |
| 30 | "Reversed the normal sex differences in brain structure and behavior" | 2003<ref name="pmid12631470"><cite style="font-style:normal">Kubo K, Arai O, Omura M, Watanabe R, Ogata R, Aou S (2003). "Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats". Neurosci. Res. 45 (3): 345–56. PMID 12631470.</cite></ref> |
| 50 | U.S. human exposure limit (not a result from an animal study, but a guideline set by EPA) | 1998<ref>EPA (Environmental Protection Agency). 1988. Oral RfD Assessment: Bisphenol A. Integrated Risk Information System.</ref> |
[edit] The Lang Study
The first study of bisphenol A's effects on humans was published in September 2008 by Iain Lang and colleagues in the Journal of the American Medical Association.<ref name="Lang et al."><cite style="font-style:normal">Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D (2008). "Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults". JAMA (300). doi:.</cite></ref><ref>[1] - Plastic bottle chemical linked to heart disease</ref> The cross-sectional study of almost 1,500 people assessed exposure to bisphenol A by looking at levels of the chemical in urine. The authors found that high bisphenol A levels were significantly associated with heart disease, diabetes, and abnormally high levels of certain liver enzymes. An editorial in the same issue notes that while this preliminary study needs to be confirmed and cannot prove causality, there is precedent for analogous effects in animal studies, which "add[s] biological plausibility to the results reported by Lang et al."<ref name=JAMAVS/>
[edit] Human exposure to bisphenol A
Bisphenol A has been known to leach from the plastic lining of canned foods<ref>Template:Cite website</ref> and, to a lesser degree, polycarbonate plastics that are cleaned with harsh detergents or used to contain acidic or high-temperature liquids. While most exposure is through diet, exposure can also occur through air and through skin absorption.<ref name="Melzer et al."><cite style="font-style:normal">Lang IA Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace, Robert B, Melzer, D (2008). "Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults". JAMA (300). doi:.</cite></ref>
Studies by the CDC found bisphenol A in the urine of 95% of adults sampled in 1988–1994<ref name="pmid15811827"><cite style="font-style:normal">Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL (2005). "Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population". Environ. Health Perspect. 113 (4): 391–5. PMID 15811827.</cite></ref> and in 93% of children and adults tested in 2003–04.<ref name="pmid18197297"><cite style="font-style:normal">Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL (2008). "Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004". Environ. Health Perspect. 116 (1): 39–44. doi:. PMID 18197297.</cite></ref> Infants fed with liquid formula are among the most exposed, and those fed formula from polycarbonate bottles can consume up to 13 micrograms of bisphenol A per kg of body weight per day (μg/kg/day; see table below).<ref>Template:Cite website</ref> The most sensitive animal studies show effects at much lower doses, while the EPA considers exposures up to 50 µg/kg/day to be safe.<ref name="globemittelstaedt"/><ref>Bisphenol A - United States Environmental Protection Agency</ref>
Consumer groups recommend that people wishing to lower their exposure to bisphenol A avoid canned food and polycarbonate plastic containers (which shares resin identification code 7 with many other plastics) unless the packaging indicates the plastic is bisphenol A-free.<ref>http://www.loe.org/shows/segments.htm?programID=08-P13-00038&segmentID=4</ref> The National Toxicology Panel recommends avoiding microwaving food in plastic containers, putting plastics in the dishwasher, or using harsh detergents, to avoid leaching. <ref>FDA Weighs Safety Of Bisphenol A</ref>
| Population | Estimated daily bisphenol A intake, μg/kg/day. Table adapted from the National Toxicology Program Expert Panel Report.<ref name="CERHR"/> |
|---|---|
| Infant (0–6 months) formula-fed | |
| Infant (0–6 months) breast-fed | |
| Infant (6–12 months) | |
| Child (1.5–6 years) | |
| Adult | |
[edit] Government and industry response
Template:Globalize/North America
[edit] Canada
After the release of the Health Canada assessment in April 2008, Canadian Health Minister Tony Clement announced Canada's intent to ban the import, sale, and advertisement of polycarbonate baby bottles containing bisphenol A due to safety concerns, and investigate ways to reduce BPA contamination of baby formula packaged in metal cans. While the agency concluded that human exposures were less than levels believed to be unsafe, the margin of safety was not high enough for formula-fed infants.<ref name=HealthCanada/><ref>The government will evaluate whether the ban will become law in October 2008. Template:Cite news</ref> 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.<ref>Wal-Mart to pull baby bottles made with chemical BPA: Washington Post, Market Watch, April 18, 2008.</ref> Nalgene also announced it will stop using the chemical in its products,<ref>Bottle Maker to Stop Using Plastic Linked to Health Concerns, New York Times, April 18, 2008.</ref> and Toys-R-Us said it too will cease selling baby bottles made from it.<ref>Template:Cite news</ref> Subsequent news reports showed many retailers removing polycarbonate drinking products from their shelves.<ref>CANOE - CNEWS - Politics: Bisphenol A water-bottle removal expanding among Canadian retailers</ref>
The federal government has formally declared bisphenol A a hazardous substance as of October 2008 and is now placed on its list of toxic substances. Health officials wrote in Canada Gazette that "It is concluded that bisphenol A be considered as a substance that may be entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health."<ref>Template:Cite news</ref> The federal ministries of health and the environment announced they would seek to restrict imports, sales and advertising of polycarbonate baby bottles containing BPA.<ref>Template:Cite news</ref>
[edit] United States
[edit] April 2008
As of the release of NTP and Health Canada reports in April, 10 U.S. states, including California,<ref>Bill List</ref> Maryland,<ref name="WaPo"/> Connecticut<ref name='courant'>Template:Citation.</ref> and New Jersey,<ref>Template:Citation.</ref> already had legislation pending that would affect the use of BPA. 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.<ref name="WaPo"/> 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,<ref>Congressional Probe Targets Consulting Group, Integrity in Science Watch, Center for Science in the Public Interest, 02/11/2008.</ref> and the Energy and Commerce Committee in the House of Representatives is investigating the use of BPA 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." The FDA maintained that bisphenol A is safe and did not recommend that people avoid using products made from it. The Consumer Product Safety Commission agreed, and its deputy director stressed that use of bisphenol A based plastics has many practical benefits and that "a ban could result in less effective protection of children from head, eye, or bodily injury."<ref name=C&ENews/> FDA then announced it would set up a task force to address these concerns, and in August it released a draft finding<ref>[http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-0038b1_01_02_FDA%20BPA%20Draft%20Assessment.pdf DRAFT ASSESSMENT OF BISPHENOL A FOR USE IN FOOD CONTACT APPLICATIONS], US Food and Drug Administration, undated.</ref> concurring with its initial position that the chemical is safe. The agency will make its final decision after an advisory panel on the issues is convened in September.<ref>Template:Cite news</ref>
In response to these events, an American Chemistry Council (ACC)/BPA Global Group (an industry trade association) 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."<ref>Canada bans BPA plastic from baby bottles, The Washington Post, Apr. 19, 2008 .</ref> The ACC said that bisphenol A does not pose a risk to consumers and 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."<ref name='courant'/> The Grocery Manufacturers Association also insisted 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."<ref>Template:Cite news</ref> A spokesman for the tin can industry said that without lining cans with bisphenol A based resins, E. coli and botulism poisoning would be "rampant."<ref name=C&ENews/>
[edit] September 2008
In September, the NTP finalized their report on bisphenol A, finding "some concern" that infants were at risk from exposure to the chemical.<ref name=NTP08/> At the same time, the FDA reassured consumers that it was safe, but convened an outside panel of experts to review the issue. The Lang study was also released that month, and David Melzer, a co-author of the study, presented the results of the study before the FDA panel.<ref name="WaPoDos">Template:Cite news</ref>
The editorial accompanying the Lang study's publication in JAMA criticized the FDA's assessment of bisphenol A: "A fundamental problem is that the current ADI [acceptable daily intake] for BPA is based on experiments conducted in the early 1980s using outdated methods (only very high doses were tested) and insensitive assays. More recent findings from independent scientists were rejected by the FDA, apparently because those investigators did not follow the outdated testing guidelines for environmental chemicals, whereas studies using the outdated, insensitive assays (predominantly involving studies funded by the chemical industry) are given more weight in arriving at the conclusion that BPA is not harmful at current exposure levels."<ref name=JAMAVS/>
The Union of Concerned Scientists similarly criticized the agency saying, "We're concerned that the FDA is basing its conclusion on two studies while downplaying the results of hundreds of other studies...This appears to be a case of cherry-picking data with potentially high cost to human health."<ref name="WaPoDos"/> The chemical industry had earlier been criticized by Democrats and their allies. David Michaels, who served in the Clinton Administration, 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."<ref name="WaPo"/> Diana Zuckerman, president of the National Research Center for Women and Families, also criticized the FDA stating "At the very least, the FDA should require a prominent warning on products made with BPA". <ref>Szabo, Liz. "Scientists, FDA face off over safety of BPA in consumer plastics". 'USA Today. September 17, 2008. Retrieved October 29, 2008</ref>
In contrast, the American Chemistry Council, the manufacturing industry's lobby group, was skeptical of the latest study: "Due to inherent limitations in study design, this new study cannot support a conclusion that bisphenol A causes any disease...The weight of scientific evidence continues to support the conclusion of governments worldwide that bisphenol A is not a significant health concern at the trace levels present in some consumer products."<ref name="WaPoDos"/>
[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.<ref name=fox><cite style="font-style:normal">Fox, J.E., J. Gulledge, E. Engelhaupt, M.E. Burrow & J.A. McLachlan (2007). "Pesticides reduce symbiotic efficiency of nitrogen-fixing rhizobia and host plants". Proc. Nat. Acad. Sci. 104: 10282–7. doi:. PMID 17548832.</cite></ref> According to Environment 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."<ref>Bisphenol A Fact Sheet, Government of Canada. Assessed April 19, 2008.</ref>
[edit] Identification in plastics
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.<ref name=Fiege/> 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.<ref name="sciam2008"><cite style="font-style:normal">Biello D (2008-02-19). "Plastic (not) fantastic: Food containers leach a potentially harmful chemical". Scientific American 2. Retrieved on 2008-04-09.</cite></ref> (in an 8 ounce glass, boiling for an hour will give concentrations of 29 parts per trillion) Type 3 (PVC) can also contain bisphenol A as antioxidant in plasticizers.<ref name=Fiege/> Types 1 (PET), 2 (HDPE), 4 (LDPE), 5 (polypropylene), and 6 (polystyrene) do not use bisphenol A during polymerization or package forming.Template:Fact Template:Clear
[edit] General Properties
*Molecular Weight
228.29
*Molecular Formula
C15H16O2
*IUPAC NAME
4-[2-(4-hydroxyphenyl)propan-2-yl]phenol
*Canonical Smiles
CC(C)(C1=CC=C(C=C1)O)C2=CC=C(C=C2)O
*Isomeric Smiles
[edit] PhysioChemical Properties
*Melting Point
153(EXP)
*LogP
3.32(EXP)
*Water Solubility
120(EXP) at 25C
[edit] References
[edit] External links
- US FDA statement on bisphenol A
- Plastics chemical alters female brains
- Frontline Fooling With Nature, interview Fredrick Vom Saal, Ph.D.
- News report on effect through plastic bottles
- Bisphenol A. A Known Endocrine Disruptor WWF publication
- Plastics Industry Bisphenol A information site
- United States Environmental Protection Agency page on Bisphenol A
- An Endocrine/Estrogen Letter special Report on BPA
- News coverage of bisphenol A from EnvironmentalHealthNews.org
- The Toxic Origins of Disease, Liza Gross, PLoS Biology - an essay examining some of the evidence and effects.
- CHEMICAL FALLOUT: JOURNAL SENTINEL WATCHDOG REPORT, Milwaukee Journal Star newspaper article examining effects of Bisphenol A on lab animals and humans.
- Safe Use Of Plastic Food Packaging And Containers, Agri-Food & Veterinary, Authority of Singapore
- Human Exposure to Bisphenol A, Vandenberg, L.N., et al. via Living on Earth
- Hazard in a bottle Attempt to regulate BPA in California defeated (from The Economist)
- The Body Toxic: How the Hazardous Chemistry of Everyday Things Threatens Our Health and Well-being, talk by journalist, Nena Baker, in Portland, Oregon, Sept. 8, 2008.
- [2]Pubchem
- [3]KEGG Compound
