Bisphenol A

Definition

Bisphenol A is an organic synthetic compound with the chemical formula (CH3)2C(C6H4OH)2. Bisphenol A, also called BPA, is classified as a high production volume (HPV) chemical, which means that it is produced or imported into the United States in quantities greater than 1 million pounds or 500 tons per year. As of 2018, about 6.8 million tons of BPA are produced each year worldwide; about a third of this total is made in the United States. Other names for BPA are p,p'-Isopropylidene bisphenol; diphenylpropane; and 2,2-Bis (4-hydroxyphenyl) propane.

Description

Bisphenol A is a colorless, white, or cream-colored solid at room temperature with a mild chemical or medicinal odor. It may take the form of flakes or crystals. It can be dissolved in acetic acid, turpentine, and other organic solvents but is poorly soluble in water. It has a melting point of 307°F–314°F (153°C–157°C) and a boiling point (at standard atmospheric pressure) of 681°F (360.5°C). BPA can also form a potentially explosive dust.

Bisphenol A is biodegradable; it has a half-life in air of less than one day and a half-life in soil and water of about 4.5 days. It is an important pollutant, however, because of the sheer amount of BPA that is manufactured and later discarded; the compound is nearly ubiquitous in the human environment.




A tiffin box or food carrier made of colorful BPA plastic materials in Thailand.





A tiffin box or food carrier made of colorful BPA plastic materials in Thailand.
(Quality Stock Arts/Shutterstock.com)
Origins

Bisphenol A was first made in 1891 by the Russian chemist Alexander Dianin (1851–1918), who condensed a 2:1 mixture of phenol and acetone in the presence of hydrochloric acid. Its synthesis was not reported, however, until 1905, when Theodor Zincke (1843–1928), a German chemist, published the results of his experiment in an academic journal. BPA received little scientific or medical attention, however, until 1938, when Charles Dodds (1899–1973), a British biochemist who was looking for a synthetic estrogen, recognized that BPA has estrogenic properties; he later discovered a more powerful estrogenic compound—diethylstilbestrol or DES.

BPA, however, was never developed for use as a drug; instead, industrial chemists in Switzerland and the United States found in 1953 that BPA could be used to synthesize epoxy resins. After the synthesizing process was patented in 1955, BPA became widely used on an industrial scale to make resins used as protective coatings on metal equipment, piping, steel drums, and the linings of food cans, as well as adhesives used for flooring. Epoxy resins made from BPA were also used eventually to make dental sealants and composites (materials used in fillings).

The next stage in the development of BPA for use in consumer products also began in 1953, when the German scientist Hermann Schnell discovered that BPA would react with phosgene (carbonyl dichloride) to form a polymerized hard plastic called polycarbonate. Patented in Germany under the name Makrolon and later in the United States under the trade name Lexan, polycarbonate proved to have a wide range of medical, military, construction, and general consumer applications. It is a good electrical insulator; it is also flame-retardant and heat-resistant. Optical-quality polycarbonate is clear as well as hard and can be used to make shatter-resistant windows, eyeglass lenses, swimming goggles, and safety visors.

Demographics

Due to the large-scale production of BPA since the 1950s and the growing number of uses for both the resins and polycarbonate plastics made from it, most people in the world have been exposed to some type of material made from BPA. Most consumers, however, have low levels of exposure to BPA, primarily from eating foods or drinking beverages from cans lined with resins made from BPA or polycarbonate bottles made from BPA. Other common forms of exposure include dental work, most often the application of sealants to prevent cavities or the use of composite resins to make tooth fillings. Workers in factories that produce bisphenol A or use it to manufacture resins and polycarbonates, however, have higher levels of exposure to BPA and may inhale its dust or develop contact dermatitis from touching it. One study sponsored by the Centers for Disease Control and Prevention (CDC) and the National Institute for Occupational Safety and Health (NIOSH) reported in 2017 that workers in industries producing BPA, BPA-based resins, or BPAfilled wax were exposed to levels of BPA as much as 70 times higher than levels outside the plants.

The widespread use of bisphenol A in consumer goods, coupled with its early history as a xenoestrogen, a synthetic compound that imitates the activity of the female hormone estrogen, led to a series of investigations into its safety beginning in the 1990s.

Investigations and controversies

It was not until 1993 that BPA's role as a xenoestrogen sparked another round of investigations. In that year, endocrinologist David Feldman at Stanford University discovered that BPA was present inside polycarbonate flasks used to culture yeast cells. The flasks had been sterilized at high temperatures, and Feldman was able to confirm that the bisphenol A in the culture medium came from the polycarbonate flasks and not from the yeast cells. The discovery that heat exposure could cause BPA to leach (be dissolved by a percolating liquid) into the contents of polycarbonate containers was followed by findings that BPA can also leach into the environment from the epoxy resins used to line tin cans and from items made of plastics containing BPA that were discarded in landfills. Last, it was found that plastics made from BPA contain some free unpolymerized molecules of the compound, which contributes to its solubility in groundwater.

In 2003 and 2004, scientists from the Centers for Disease Control and Prevention (CDC) measured the levels of BPA in the urine of 2,500 Americans over six years of age who participated in the National Health and Nutrition Examination Survey (NHANES). It was found that 93% of the subjects had measurable levels of BPA, which indicated how widespread the compound is in consumer products made and used in the United States. Finding measurable levels of BPA, however, does not necessarily indicate negative health effects. But in 2008, the NTP undertook another review of bisphenol A for four reasons: 1) its status as an HPV chemical; 2) the evidence from the NHANES study that almost all Americans are exposed to BPA; 3) the publication of scientific papers documenting BPA effects on animal reproduction and development; and 4) the growing level of public concern about the possible effects of BPA in humans.

The 2008 NTP study concluded that because adult humans metabolize bisphenol A more efficiently as they age, the greater concern is that exposure to BPA may have more significant effects in children than in adults, specifically, effects on the development of the brain and the prostate gland, as well as the potential for behavioral disorders. The report stated that bisphenol A may alter human development. But with the exception of minimal concern for workplace exposures to BPA, the researchers stated that adult exposures to BPA in the workplace was not particularly worrisome.

The 2008 NTP report touched off a flood of newspaper articles and worldwide concern about the safety of polycarbonates and resins made from BPA in baby bottles, pacifiers, toys, and other objects that small children might put in their mouths. Between 2010 and 2012, such countries as Denmark, France, Australia, and Turkey banned the use of baby bottles made from polycarbonates, as did the European Food Safety Authority (EFSA).

In the United States, the FDA amended its food packaging regulations in 2012 to no longer approve BPA-based polycarbonate resins in baby bottles and cups. This change was followed in 2013 by a similar amendment to disallow the use of BPA-based epoxy resins as coatings in packaging for infant formula. The wording of the FDA statements is significant, as the agency noted that its amendments were based on information that the food packaging industry had voluntarily abandoned the use of materials containing BPA—not on safety considerations. “An amendment of the food additive regulations based on abandonment is not based on safety, but is based on the fac that the regulatory authorization is no longer necessary for the specific use of the food additive because that use has been permanently and completely abandoned.”

As of 2018, concern about the activity of BPA as an endocrine disruptor was ongoing. The scientific papers that were published prior to the 2008 NTP report comprised animal studies that reported such findings as lowered sperm counts in male mice and frogs; damage to both sperm and eggs in minnows; and changes in mating behavior in deer mice. BPA was found to cross the placental barrier in rats and mice and has been detected in human maternal and fetal serum and in human placental tissue. It was not yet known, however, whether BPA affects human fetal development or how it might do so. The European Food Safety Authority (EFSA) stated in 2015 that its experts “concluded that scientific knowledge of how BPA behaves in humans was still unclear and there was no single explanation for how BPA potentially affects humans.” A reevaluation of the EFSA position on the potential endocrine disruption hazards of BPA was scheduled to begin at some time in 2018.

The search for acceptable substitutes for BPA in food packaging began as early as 1998, when the Japanese canning industry began voluntarily to replace can liners made of BPA epoxy resins with polyethylene terephthalate (PET), which is BPA-free. A subsequent study carried out in South Korea proposed the use of either 1,4-cyclohexanedimethanol (CHDM) or terephthalic acid (TPA) as suitable replacements for BPA.

Purpose

Polycarbonate products, which account for almost three-fourths of bisphenol A production, are used in construction (glazing, dome lights, noise barriers); data storage (CDs, DVDs, Blu-ray discs); safety and security (safety lenses in eyeglasses and protective visors and helmets for use in baseball, hockey, snowboarding, and other sports); electronic equipment (housing units for cell phones, laptops, tablets, and other mobile devices); medical devices (incubators, laboratory equipment, etc.); automobile and aircraft parts, including cockpit canopies for fighter jets; and niche applications such as lightweight luggage, fountain pens, security wrapping for small items, and police riot shields. Manufacturers of food and beverage containers, however, were as of 2018 investigating the use of polycarbonates made with phenols other than BPA.

Epoxy resins, which account for about one-fifth of BPA production, are widely used to line pipes and storage tanks; to produce circuit boards and paints; and to provide protective linings in food and beverage cans.

Free (non-polymerized) BPA is used to make thermal paper used to provide customer receipts at the point of sale. Because the BPA in this type of paper is not polymerized, it can be transferred to skin when the paper is touched. There is additional concern that BPA from this paper could be introduced into the body by hand-to-mouth contact.

Causes and symptoms/effects

Causes

Bisphenol A can enter the human or natural environment in a number of possible ways:

Symptoms/effects

Bisphenol A has been reported by NIOSH to have the following effects in workers exposed to it:

Protective measures and treatment

NIOSH recommends the following protective measures and treatment for workers exposed to BPA, particularly dust containing the compound:

KEY TERMS
Acetone—
An organic solvent used in the production of bisphenol A. It is familiar to most people as the active ingredient in nail polish remover and paint thinner.
Carcinogen—
Any substance, form of radiation, or radioactive material that promotes the evelopment of cancer.
Contact dermatitis—
A localized rash or irritation of the skin caused by contact with a foreign substance, usually an allergen or a chemical irritant.
Endocrine disruptor—
Any chemical that can interfere with the endocrine system in the human body or the hormones it produces naturally. BPA is considered an endocrine disruptor.
Endocrine system—
The body system that produces and secretes hormones that regulate such processes as development, reproduction, energy balance, and response to stress. It includes such organs as the pancreas, thyroid gland, pituitary gland, pineal gland, adrenal glands, and the ovaries (in women) and testes (in men).
High production volume (HPV) chemical—
Any chemical produced or imported into the United States in quantities greater than 1 million pounds or 500 tons per year. BPA is classified as an HPV chemical.
Leach—
To remove a chemical compound from a substance by the action of a percolating liquid. BPA can leach from polycarbonate containers under conditions of high heat, the presence of ethanol, and the age of the container.
Monomer—
A molecule of low molecular weight capable of reacting with other molecules of low molecular weight to form large molecules called polymers.
Phenol—
An acid used in the manufacture of plastics. It was originally made from coal tar but subsequently made primarily from petroleum.
Phosgene—
A colorless gas used in the manufacture of polycarbonate plastics from BPA. Also known as carbonyl dichloride, phosgene became infamous during World War I for its use as a chemical weapon; it caused the death of an estimated 85,000 French and British soldiers. Because of its obvious safety issues, phosgene is usually produced within the same plant where it is used, and extreme care is taken to contain it.
Polycarbonate—
A type of thermoplastic polymer made from BPA that contains carbonate groups in its structure. Its clarity and toughness have led to its use in a wide variety of safety applications as well as general consumer goods.
Polymer—
Any of a class of very large natural or synthetic molecules formed from multiples of monomers.
Resin—
A solid or sticky (viscous) substance of either plant-derived or synthetic origin that can be converted into polymers. Many trees secrete resins in response to injury to protect themselves from insect invasion. BPA is used to make epoxy resins among other products.
Thermoplastics—
Polymer plastics that become pliable when heated above a specific temperature and become solid upon cooling.
Xenoestrogens—
Naturally occurring or synthetic compounds that have estrogen-like properties. BPA is a synthetic xenoestrogen.

Diagnosis

The level of a person's exposure to BPA can be measured from samples of urine (the most common method), blood serum, or sweat. As of 2018, however, there was no indication that measurable levels of BPA in human body fluids can be used to predict long-term health effects.

Prevention

The NIEHS suggests that parents who are concerned about the greater susceptibility of newborns and infants to the effects of BPA can take the following steps to reduce children's exposure to the chemical:

Precautionary regulations

Government regulations regarding the manufacture, use of, and exposure to bisphenol A in North America and Europe as of 2018 were as follows:

See also Acetone ; Food safety ; Toxicology .

Resources

BOOKS

Cotruvo, Joseph. Drinking Water Contaminants Guidebook. Boca Raton, FL: Taylor and Francis, 2018.

Gibert, Yann, editor. Bisphenol A: Sources, Risks of Environmental Exposure, and Human Health Effects. New York: Nova, 2015.

Vogel, Sara A. Is It Safe? BPA and the Struggle to Define the Safety of Chemicals. Berkeley: University of California Press, 2013.

PERIODICALS

Beausoleil, C., et al. “Regulatory Identification of BPA as an Endocrine Disruptor: Context and Methodology.” Molecular and Cellular Endocrinology. Published electronically February 6, 2018. doi: 10.1016/j.mce.2018. 02.001.

Chianese, R., et al. “Bisphenol A in Reproduction: Epigenetic Effects.” Current Medicinal Chemistry 25 (February 21, 2018): 748–70.

Fugolin, A. P. P., and C. S. Pfeifer. “New Resins for Dental Composites.” Journal of Dental Research 96 (September 2017): 1085–91.

Hines, C. J., et al. “Air, Hand Wipe, and Surface Wipe Sampling for Bisphenol A (BPA) among Workers in Industries that Manufacture and Use BPA in the United States.” Journal of Occupational and Environmental Hygiene 14 (November 2017): 882–97.

Hines, C. J., et al. “Urinary Bisphenol A (BPA) Concentrations among Workers in Industries that Manufacture and Use BPA in the USA.” Annals of Work Exposures and Health 81 (March 2017): 164–82.

Liu, J., and J. W. Martin. “Prolonged Exposure to Bisphenol A from Single Dermal Contact Events.” Environmental Science and Technology 51 (September 5, 2017): 9940–49.

Masoner, J. R., et al. “Landfill Leachate as a Mirror of Today's Disposable Society: Pharmaceuticals and Other Contaminants of Emerging Concern in Final Leachate from Landfills in the Coterminous United States.” Environmental Toxicology and Chemistry 35 (April 2016): 906–18.

Nesan, D., L. C. Sewell, and D. M. Kurrasch. “Opening the Black Box of Endocrine Disruption of Brain Development: Lessons from the Characterization of Bisphenol A.” Hormones and Behavior. Published electronically January 3, 2018. doi: 10.1016/j.yhbeh.

Son, S., et al. “Cytotoxicity Measurement of Bisphenol A (BPA) and Its Substitutes Using Human Keratinocytes.” Environmental Research 164 (July 2018): 655–59.

WEBSITES

American Chemistry Council. “About BPA.” https://plastics.americanchemistry.com/Product-Groups-and-Stats/PolycarbonateBPA-Global-Group/AboutBPA.pdf (accessed April 23, 2018).

American Chemistry Council. “About BPA: Polycarbonate Plastic.” https://plastics.americanchemistry.com/Product-Groups-and-Stats/PolycarbonateBPA-Global-Group/About-BPA-Polycarbonate-Plastic.pdf (accessed April 23, 2018).

Centers for Disease Control and Prevention (CDC) National Biomonitoring Program. “Bisphenol A (BPA) Factsheet.” https://www.cdc.gov/biomonitoring/BisphenolA_FactSheet.html (accessed April 23, 2018).

European Food Safety Authority (EFSA). “Bisphenol A.” http://www.efsa.europa.eu/en/topics/topic/bisphenol (accessed April 23, 2018).

National Institute of Environmental Health Sciences (NIEHS). “Bisphenol A (BPA).” https://www.niehs.nih.gov/health/topics/agents/sya-bpa/index.cfm (accessed April 23, 2018).

National Library of Medicine PubChem Open Chemistry Database. “Bisphenol A.” https://pubchem.ncbi.nlm.nih.gov/compound/6623 (accessed April 23, 2018).

National Library of Medicine TOXNET. “HSDB: Bisphenol A.” https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~CiI6K7:1 (accessed April 23, 2018).

National Toxicology Program (NTP). “Bisphenol A Research Program.” https://ntp.niehs.nih.gov/results/areas/bpa/program.html (accessed April 23, 2018).

U.S. Food and Drug Administration (FDA). “Bisphenol A (BPA): Use in Food Contact Application.” https://www.fda.gov/newsevents/publichealthfocus/ucm064437.htm#summary (accessed April 23, 2018).

ORGANIZATIONS

Agency for Toxic Substances and Disease Registry (ATSDR), 4770 Buford Hwy. NE, Atlanta, GA, 30341, (800) 232-4636, https://wwwn.cdc.gov/dcs/ContactUs/Form , https://www.atsdr.cdc.gov .

American Chemistry Council, 700 Second St. NE, Washington, DC, (202) 249-7000, Fax: (202) 249-6100, https://www.americanchemistry.com/ .

Centers for Disease Control and Prevention (CDC), 1600 Clifton Rd., Atlanta, GA, 30329, (800) CDC-INFO, http://www.cdc.gov .

European Food Safety Authority (EFSA), Via Carlo Magno 1A, Parma, Italy, 43126 Parma, +39 0521 036111, http://www.efsa.europa.eu/en/contact/askefsa , http://www.efsa.europa.eu/ .

International Programme on Chemical Safety (IPCS), Avenue Appia 20, Geneva, Switzerland, 1202 Geneva, +41 22 791211, http://www.who.int/ipcs/en/ .

National Institute of Environmental Health Sciences (NIEHS), 111 T. W. Alexander Dr., Durham, NC, 27709, (919) 541-3345, Fax: (301) 480-2978, webcenter@niehs.nih.gov, https://www.niehs.nih.gov .

U.S. Environmental Protection Agency (EPA), 1200 Pennsylvania Ave. NW, Washington, DC, 20460, (202) 564-4700, https://www.epa.gov .

U.S. Food and Drug Administration (FDA), 10903 New Hampshire Ave., Silver Spring, MD, 20993, (888) 463-6332, https://www.fda.gov , https://www.fda.gov .

Rebecca J. Frey, Ph.D.

  This information is not a tool for self-diagnosis or a substitute for professional care.