Bisphenol A

At a Glance

Bisphenol A (BPA) is an endocrine-disrupting compound and a reproductive toxicant. It’s one of the most common chemicals we’re exposed to each day, and it’s in everything from food and drink containers to dental fillings. BPA can disrupt the hormone system, particularly when exposures occur during prenatal development and infancy. The FDA has banned BPA from baby bottles and infant formula packaging.

What is BPA?

BPA is a synthetic estrogen that can disrupt the hormone system. It is an unstable, lipophilic (fat-seeking) compound that can leach into food products, especially when heated,[1] and food products contaminated with this chemical are thought to be a major source of BPA exposure.[2],[3] Some BPA alternatives, such as bisphenol S (BPS), have come on the market, but have not been proven safe, as they, too, may cause endocrine disruption.[4],[5]

Where is BPA found?

BPA is common in many everyday products, including polycarbonate plastic (widely used in clear plastic containers, eyeglasses, and other household products), dental sealants, thermal receipts, consumer products such as CDs and sports equipment, and epoxy resins used to line food cans.[6] Significant levels have also been measured in ambient air,[7] house dust,[8] and river and drinking water.[9]

BPA can be ingested into the body through food and drink packaged in materials containing BPA. Studies have found rapid increases in BPA levels in urine and blood samples taken from subjects who intentionally increased their intake of food and drinks packaged in BPA-containing products.[10], [11]  Another study demonstrated that limiting the intake of commercially packaged food significantly decreased BPA levels in the body.[12]

While food is a major source of BPA, studies of fasting individuals indicate that other sources of BPA exist in everyday environments.[13] BPA has been shown to rapidly absorb into the skin upon brief contact with items such as BPA-containing thermal receipts.[14]

What evidence links BPA to breast cancer?

BPA is ubiquitous in our environment. It is a reproductive toxicant on California’s Proposition 65 Chemicals of Concern list.[15] Many studies have revealed the accumulating evidence linking BPA exposure to breast cancer.

  • Although BPA has a rapid clearance rate from the body (hours to days),[16] studies have found it in blood and urine samples of pregnant women,[17],[18],[19] breast milk,[20], [21] amniotic fluid,[22] placental tissue and umbilical cord blood at birth,[23],[24] and the urine of premature infants.[25] This is quite concerning, considering the growing evidence linking BPA to adverse health effects.
  • Several studies on rats and mice have found that prenatal exposure to BPA can lead to abnormalities in mammary tissue development. These aberrations were observable during gestation and were maintained into adulthood.[26],[27],[28]
  • Many studies using both rat and mouse models have demonstrated that even brief exposures to doses of BPA on par with those measured in everyday settings during gestationor around the time of birth lead to changes in mammary tissue structure predictive of later development of tumors.[29],[30],[31]
  • Prenatal exposure of rats to BPA resulted in an increase in pre-cancerous lesions and abnormal cell groups[32], [33] as well as an increased number of mammary tumors following adult exposures to sub-threshold doses of known carcinogens.[34],[35] Later studies demonstrated that BPA alone also increased the growth of mammary tumors, without the addition of known carcinogens.[36]
  • Some data suggest that during the time between conception and birth, BPA alters the content and expression of several proteins in some cells, which ultimately modifies gene expression in the mammary gland.[37], [38]
  • Studies have shown that the mammary glands of mice exposed to BPA as newborns were more sensitive to estrogen and progesterone during puberty.[39],[40]
  • Some of the long-term effects of neonatal exposures to BPA may be dose dependent, with low- and high-dose exposures resulting in different timingand profiles of changes in gene expression in cells of the mammary gland. In one study, low-dose exposures had the most profound effect on rat mammary glands during the period just before reproductive maturity, while higher doses had more delayed effects, altering gene expression in the mammary tissues of mature adults.[41]
  • Prenatal exposure of mice to BPA may reduce the immune responses that commonly target developing cancer cells.[42]
  • Exposure to low levels of BPA in normal and cancerous human breast cells led to altered gene expression including cell death, rapid increase in cell formation, and the initiation of cancer formation.[43],[44],[45]In the presence of BPA, highly aggressive tumors were developed in cells from the non-cancerous breast of women diagnosed with breast cancer.[46]

Who is most likely to be exposed to BPA?

BPA exposure is widespread and present in many parts of our everyday environment. Individuals who consume foods packaged in cans or use polycarbonate water bottles or baby bottles may have higher exposures. Individuals who work with thermal cash register receipts may absorb BPA through their skin.

Who is most vulnerable to the health of effects of BPA?

Studies on rats and mice have found that BPA exposure during pregnancy has been shown to significantly impact fetal development.[47],[48],[49],[50],[51],[52],[53],[54]

BPA has been found to reduce the effectiveness of common chemotherapy agents (cisplatin, doxirubicin and vinblastin) in blocking the proliferation of human breast cancer cells when tested in vitro.[55], [56]

What are the top tips to avoid exposure?

Luckily, clearance of BPA from the body is quite rapid. One study demonstrated that just a three-day period of limiting intake of packaged foods decreased the concentrations of BPA found in urine by an average 65 percent.[57]

Beginning to make these simple changes can help prevent exposure:

  • Avoid canned foods. Where fresh alternatives are not available, choose frozen.
  • Avoid clear, shatterproof plastic food and drink containers (sometimes labeled with the recycling code 7).
  • Avoid handling thermal receipts.
  • Choose BPA-free baby bottles and child cups. It is important to be aware that the alternatives to BPA have not been adequately tested. Glass and stainless steel containers are your safest bet. BPA-free labels unfortunately do not always mean the product is safe.

[1] Brotons, J.A., Olea-Serrano, M.F., Villalobos, M., Pedraza, V., Olea, N. (1995). Xenoestrogens released from lacquer coatings in food cans. Environ Health Perspect, 103, 608-12.

[2] Lakind, J.S., Naiman, D.Q. (2011). Daily intake of bisphenol A and potential sources of exposure: 2005-2006 National Health and Nutrition Examination Survey. J Expo Sci Environ Epidemiol, 21, 272-9.

[3] Vandenberg, L.N., Hauser, R., Marcus, M., Olea, N., Welshons, W.V. (2007). Human exposure to bisphenol A (BPA). Reprod Toxicol, 24, 139-77.

[4] Rochester, J.R., Bolden, & A.L. (2015). Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environmental Health Perspectives (online). 1;123(7):643.

[5] Ji, K., Hong, S., Kho, Y. & Choi, K. Effects of bisphenol S exposure on endocrine functions and reproduction of zebrafish. Environmental science & technology. 2013 Jul 11;47(15):8793-800.

[6] OEHHA: Office of Environmental Health Hazard Assessment. Chemicals: Bisphenol-A. Available online: http://oehha.ca.gov/chemicals/bisphenol-a (Accessed October, 2016).

[7] Matsumoto H, Adachi S, Suzuki Y. Bisphenol A in ambient air particulates responsible for the proliferation of MCF-7 human breast cancer cells and Its concentration changes over 6 months. Arch Environ Contam Toxicol. 2005;48:459-66.

[8] Rudel RA, Camann DE, Spengler JD, Korn LR, Brody JG. Phthalates, alkylphenols, pesticides, polybrominated diphenyl ethers, and other endocrine-disrupting compounds in indoor air and dust. Environ Sci Technol. 2003;37:4543-53.

[9] Rodriguez-Mozaz S, de Alda ML, Barceló D. Analysis of bisphenol A in natural waters by means of an optical immunosensor. Water Res. 2005;39:5071-9.

[10] Carwile JL, Luu HT, Bassett LS, et al. Polycarbonate bottle use and urinary bisphenol A concentrations. Environ Health Perspect. 2009;117:1368-72.

[11] Smith R, Lourie. Slow Death by Rubber Duck: The Secret Danger of Everyday Things. 2009. Counterpoint: Berkeley, CA.

[12] Rudel RA, Gray JM, Engel CL, et al. Food packaging and bisphenol A and bis(2-ethyhexyl) phthalate exposure: findings from a dietary intervention. Environ Health Perspect. 2011;119:914-20.

[13] Stahlhut RW, Welshons WV, Swan SH. Bisphenol A data in NHANES suggest longer than expected half-life, substantial nonfood exposure, or both. Environ Health Perspect. 2009;117:784-9.

[14] Vom Saal FS, Welshons, WV. Evidence that bisphenol a (BPA) can be accurately measured without contamination in human serum and urine and that BPA causes numerous hazards from multiple routes of exposure. Molec Cell Endocr. 2014; 398:101-13.

[15] OEHHA: Office of Environmental Health Hazard Assessment. Chemicals Considered or Listed Under Proposition 65: Bisphenol A. Available online: http://oehha.ca.gov/proposition-65/chemicals/bisphenol-bpa (accessed October, 2016).

[16] Stahlhut RW, Welshons WV, Swan SH. Bisphenol A data in NHANES suggest longer than expected half-life, substantial nonfood exposure, or both. Environ Health Perspect. 2009;117:784-9.

[17] Ye X, Pierik FH, Angerer J, et al. Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa). Int J Hyg Environ Health. 2009;212:481-91.

[18] Padmanabhan V, Siefert K, Ransom S, et al. Maternal bisphenol-A levels at delivery: a looming problem? J Perinatol. 2008;28:258-63.

[19] Teeguarden JG, Twaddle NC, Churchwell MI, Doerge DR. Urine and serum biomonitoring of exposure to environmental estrogens I: Bisphenol A in pregnant women. Food Chem Toxicol. 2016;92:129-42.

[20] Kuruto-Niwa R, Ito T, Goto H, Nakamura H, Nozawa R, Terao Y. Estrogenic activity of the chlorinated derivatives of estrogens and flavonoids using a GFP expression system. Environ Toxicol Pharmacol. 2007;23:121-8.

[21] Sun Y, Irie M, Kishikawa N, Wada M, Kuroda N, Nakashima K. Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection. Biomed Chromatogr. 2004;18:501-7.

[22] Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod. 2002;17:2839-41.

[23] Environmental Working Group. Guide to BPA. 2009.

[24] Schönfelder G, Wittfoht W, Hopp H, Talsness CE, Paul M, Chahoud I. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect. 2002;110:A703-7.

[25] Calafat AM, Weuve J, Ye X, et al. Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ Health Perspect. 2009;117:639-44.

[26] Vandenberg LN, Maffini MV, Wadia PR, Sonnenschein C, Rubin BS, Soto AM. Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland. Endocrinology. 2007;148:116-27.

[27] Vandenberg LN, Maffini MV, Schaeberle CM, et al. Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod Toxicol. 2008;26:210-19.

[28] Betancourt AM, Mobley JA, Russo J, Lamartiniere CA. Proteomic analysis in mammary glands of rat offspring exposed in utero to bisphenol A. J Proteomics. 2010;73:1241-53.

[29] Markey CM, Luque EH, Munoz de Toro M, Sonneschein C, Soto AM. In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod. 2001;65:1215-23.

[30] Maffini MV, Rubin BS, Sonnenschein C, Soto AM. Endocrine disruptors and reproductive health: the case of bisphenol-A. Mol Cell Endocrinol. 2006;254-255:179-86.

[31] Muñoz-de-Toro M, Markey CM, Wadia PR, et al. Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology. 2005;146:4138-47.

[32] Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM. Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod Toxicol. 2007;23:383-90.

[33] Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats. Environ Health Perspect. 2013;121:1040-6.

[34] Durando M, Kass L, Piva J, et al. Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ Health Perspect. 2007;115:80-6.

[35] Jenkins S, Raghuraman N, Eltoum I, Carpenter M, Russo J, Lamartiniere CA. Oral exposure to bisphenol a increases dimethylbenzanthracene-induced mammary cancer in rats. Environ Health Perspect. 2009;117:910-15.

[36] Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats. Environ Health Perspect. 2013;121:1040-6.

[37] Wadia PR, Cabaton NJ, Borrero MD, et al. Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland. PLoS ONE. 2013;8:e63902.

[38] Ibrahim MAA, Elbakry RH, Bayomy NA. Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat. Int J Exp Pathol. 2016;97:27-36

[39] Wadia PR, Vandenberg LN, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM. Perinatal bisphenol A exposure increases estrogen sensitivity of the mammary gland in diverse mouse strains. Environ Health Perspect. 2007;115:592-8.

[40] Ayyanan A, Laribi O, Schuepbach-Mallepell S, et al. Perinatal exposure to bisphenol a increases adult mammary gland progesterone response and cell number. Mol Endocrinol. 2011;25:1915-23.

[41] Moral R, Wang R, Russo IH, Lamartiniere CA, Pereira J, Russo J. Effect of prenatal exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature. J Endocr. 2008;196:101-12.

[42] Fischer C, Mamillapalli R, Goetz LG, Jorgenson E, Ilagan Y, Taylor HS. Bisphenol A (BPA) Exposure In Utero Leads to Immunoregulatory Cytokine Dysregulation in the Mouse Mammary Gland: A Potential Mechanism Programming Breast Cancer Risk. Horm Cancer. 2016;7:241-51.

[43] Goodson WH, Luciani MG, Sayeed SA, Jaffee IM, Moore DH, Dairkee SH. Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women. Carcinogenesis. 2011;32:1724-33.

[44] Tilghman SL, Bratton MR, Segar HC, et al. Endocrine disruptor regulation of microRNA expression in breast carcinoma cells. PLoS ONE. 2012;7:e32754.

[45] Weng Y-I, Hsu P-Y, Liyanarachchi S, et al. Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010;248:111-21.

[46] Dairkee SH, Seok J, Champion S, et al. Bisphenol A induces a profile of tumor aggressiveness in high-risk cells from breast cancer patients. Cancer Res. 2008;68:2076-80.

[47] Maffini MV, Rubin BS, Sonnenschein C, Soto AM. Endocrine disruptors and reproductive health: the case of bisphenol-A. Mol Cell Endocrinol. 2006;254-255:179-86.

[48] Muñoz-de-Toro M, Markey CM, Wadia PR, et al. Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology. 2005;146:4138-47.

[49] Vandenberg LN, Maffini MV, Schaeberle CM, et al. Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod Toxicol. 2008;26:210-19.

[50] Betancourt AM, Mobley JA, Russo J, Lamartiniere CA. Proteomic analysis in mammary glands of rat offspring exposed in utero to bisphenol A. J Proteomics. 2010;73:1241-53.

[51] Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM. Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod Toxicol. 2007;23:383-90.

[52] Acevedo N, Davis B, Schaeberle CM, Sonnenschein C, Soto AM. Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats. Environ Health Perspect. 2013;121:1040-6.

[53] Wadia PR, Vandenberg LN, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM. Perinatal bisphenol A exposure increases estrogen sensitivity of the mammary gland in diverse mouse strains. Environ Health Perspect. 2007;115:592-8.

[54] Ayyanan A, Laribi O, Schuepbach-Mallepell S, et al. Perinatal exposure to bisphenol a increases adult mammary gland progesterone response and cell number. Mol Endocrinol. 2011;25:1915-23.

[55] Lapensee EW, Tuttle TR, Fox SR, Ben-Jonathan N. Bisphenol A at low nanomolar doses confers chemoresistance in estrogen receptor-alpha-positive and -negative breast cancer cells. Environ Health Perspect. 2009;117:175-80.

[56] LaPensee EW, LaPensee CR, Fox S, Schwemberger S, Afton S, Ben-Jonathan N. Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells. Cancer Lett. 2010;290:167-73.

[57] Rudel RA, Gray JM, Engel CL, et al. Food packaging and bisphenol A and bis(2-ethyhexyl) phthalate exposure: findings from a dietary intervention. Environ Health Perspect. 2011;119:914-20.

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