What You and Your Patients Need to Know About Bisphenol A
Bisphenol A (BPA) is an environmental estrogen that can affect development and health by disrupting normal hormonal signaling. Estrogen, working at very low blood concentrations, triggers responses in cells and tissues and is critical during fetal development and in normal health and reproduction. BPA binds to the same cellular receptors as estrogen and may lead to detrimental health effects.
In June of this year, the American Medical Association formally recognized BPA as an endocrine-disrupting agent. Physicians can play an important role in educating their patients about this pervasive environmental contaminant. The first steps are to understand the potential health risks of BPA and how to limit those risks through simple lifestyle changes.
BPA is used in the production of polycarbonate plastics and epoxy resins. Many consumer products, such as some reusable water bottles, baby bottles, toys, cell phones, and DVDs, contain BPA. BPA is also found in the inner linings of metal food cans.1 The epoxy lining protects the metal can from rust and corrosion which may taint the food. It is present in various medical devices as well, including incubators, blood oxygenators, and dialysis machines. Given its wide uses, BPA ranks among the highest volume chemicals manufactured worldwide.
Although present in countless products, none of which is intended for consumption, the primary route of exposure is through ingestion. BPA has been shown to leach from products that contain it, such as food cans, into the foodstuffs stored in the container.1,2 When the food is then consumed, BPA enters the body through the digestive tract.
A 2007 survey by the Centers for Disease Control found that approximately 92% of Americans have detectable levels of BPA in their bodies.3 The survey is considered representative of the United States population even though it included only people older than six years old. It is notable, however, that the children (ages 6-11 years) in this study displayed the highest levels of BPA of all populations investigated. BPA has been found in placental tissue and fetal blood as well, indicating that fetuses are being exposed as a result of maternal exposure.4 An additional study looked at the levels of BPA in infants – specifically in premature infants housed in Neonatal Intensive Care Units.5 It was found that these infants displayed the highest level of BPA in their bodies of all populations.
Exposure to BPA has been studied on many levels, from effects on individual cells, to tissues and whole organisms. While most health studies regarding exposure to BPA are done in laboratory animals, the few human epidemiological studies reveal a relationship between BPA exposure and polycystic ovary syndrome, repeated miscarriage, and heart disease.6-8 Additionally, BPA causes a human breast cancer cell line to proliferate, suggesting that estrogen-sensitive tissues and cells in the human body may react similarly.9
Many animal studies focus on the effect of BPA exposure during fetal development as this is a time when cells and tissues are especially susceptible to alterations in the hormonal environment. Not only does BPA disrupt proper functioning of the placenta during gestation, but offspring of animals that are exposed to BPA during pregnancy exhibit many deleterious health effects.10 Male offspring have enlarged prostates and malformed urethra.11, 12 Moreover, they are at a higher risk of developing prostate cancer. BPA exposure alters the genital tract of female offspring.11, 12 Exposed females also enter puberty earlier.12 Exposure affects brain development and, as a result, some behavioral differences typically seen between males and females are lost in offspring exposed to BPA in the uterus.13
Based on the clear effects of BPA exposure on the development of fetuses in animals, similar effects on human development are plausible. Indeed, BPA has been found in the bloodstream, placenta, cord blood, and fetal blood of humans at levels that are within the range studied in many of the animal models.5
While hundreds of studies, most focusing on animal models, point to the harmful health effects of BPA, there has been controversy over the past decade and a half regarding safety of the compound in humans. Nevertheless, scientific review panels have determined that some detrimental health effects may occur in humans.14-16 Likely human health effects that have been vetted through these review panels include advanced puberty in females14, 15 , effects on the brain and behavior15, 16, mammary gland and prostate abnormalities, and reproductive effects in males and females.
Beyond the immediate developmental effects of BPA exposure in utero, evidence is beginning elucidate long-term effects of early-life exposure to BPA, potentially through the modification of epigenetic programming via altered DNA methylation.16, 17 One study suggests that such detrimental modifications may be counteracted by maternal nutrient supplementation.18 Nevertheless, these changes may result in alterations that are passed on transgenerationally, resulting in adverse health effects in subsequent generations who, themselves, may not have been directly exposed to BPA.17, 19
Given the putative adverse health effects of BPA exposure, the U.S. Environmental Protection Agency added BPA to its “Chemicals of Concern” list under the Toxic Substances Control Act in 2010.20 The U.S. Department of Health and Human Services website also posted “Information for Parents” on how to minimize their infant’s exposure to BPA.21
Humans are typically exposed to about 0.001 milligrams of BPA per kilogram of body weight per day. This is 50 times lower than the ‘safe’ limit set by the EPA and the Food and Drug Administration. Unfortunately, this level of exposure is still significantly higher than the low doses that have been shown to cause adverse health effects.
The concern of exposure is highest when fetuses, infants, and children are considered because of the adverse effects of BPA on normal developmental processes early in life.
It is clear that infants and children are burdened with the highest levels of BPA. This is likely due to several factors. First, the ability infants and children to metabolically detoxify contaminants such as BPA is not yet mature. While BPA will ultimately be removed from the blood through a liver-mediated process, BPA stays in the system of infants and children longer than in adults.16 Second, when compared to adults, infants and children consume proportionately more food when their overall body size is taken into account and therefore bodily concentrations are higher. The milk, formula, or food that is the main staple of an infant may be stored in containers (baby bottles, sippy cups) that are made with BPA.3, 22, 23 Infants and young children are also more likely to mouth plastic products, such as toys, that are not necessarily meant to be put in the mouth.
BPA can also pass from the mother to the fetus.5 In addition, breast milk can transmit BPA to an infant.24 Given this, it is not only the child, but the pregnant or nursing mother, that need to be protected from BPA exposure. Since the children cannot be responsible for making choices regarding BPA, clear information must be provided to parents (and potential parents) so that they can made the educated choices needed to protect themselves and their children.
Fortunately, BPA is metabolized and cleared from the body so decreasing daily exposure to BPA can make a difference in overall body levels.25, 26 In Japan, industries voluntarily reduced BPA use in their products between 1998 and 2003 and studies showed a dramatic decline in body levels of BPA in the population.27, 28 Educating your patients about a few simple lifestyle changes can make a difference in their overall BPA exposure and potentially reduce their risk for adverse health effects.
First, opting for fresh and frozen food rather than canned food is a big step. 22 While damage and age of food cans does not appear to greatly increase the amount of BPA leached into food, the initial packaging and sterilization techniques do release significant levels of BPA into canned food.22, 1
Second, minimizing the use of polycarbonate plastics food and beverage containers will also help. Polycarbonate plastics are usually hard, clear, and shatter-resistant. They may be labeled with recycle number 7, although not all number 7 products contain BPA.
Third, learning about the proper care and use of containers can curtail exposure. Heat and wear increases the leaching rate of BPA into the food or beverage stored in the container, so polycarbonate plastics should not be microwaved or put through the dishwasher and they should not be used if visibly scratched.29, 2
Parents and caregivers should also be provided information in protecting infants and children from unnecessary BPA contact. Powdered infant formula is usually not stored in containers made from BPA, but some premade liquid infant formulas are packaged in BPA-containing bottles, and such formula has been shown to be tainted.24 In September 2011, a report from the Breast Cancer Fund revealed that many children’s canned food items contained BPA.30
Children are also more likely to mouth plastic products, such as toys or the hard plastic portion of a pacifier. Caregivers should be mindful of products aimed at children that may contain BPA, such as sippy cups, tableware, and toys.3, 22, 26 Thankfully, manufacturers are increasingly labeling products as “BPA-free”. The American Medical Association adopted a new policy in 2011 supporting continued industry efforts to produce BPA-free baby products as well as a total ban on the sale of such products.
As of 2011, ten states have passed legislation limiting the use of BPA in products aimed at children. Pennsylvania has similar legislation, spearheaded by Representative Lawrence Curry, that is currently in the House Health Committee. In New Jersey, Senator Linda Greenstein introduced a related bill in 2010 that has been referred to the Senate Commerce Committee.
While the current BPA legislation is an important step, the direct education of patients about BPA and the simple steps that can be taken to minimize their BPA exposure may lead to health improvements within the community.
Rebecca Roberts, Ph. D., is an Associate Professor in the Department of Biology and Coordinator of the Biochemistry and Molecular Biology Program at Ursinus College in Collegeville, PA, where she studies the effect of hormonal regulation of the immune system, with a focus on the roles of estrogen and bisphenol A in Systemic Lupus Erythematosus. She has been active in educating the public about bisphenol A and recently presented expert testimony to the Pennsylvania House of Representatives Democratic Policy Committee regarding toxin-free toddler and baby products.
1. Goodson, A., H. Robin, W. Summerfield, and I. Cooper, 2004. Migration of bisphenol A from can coatings – effects of damage, storage conditions and heating. Food Addit Contam, v. 21(10), pp. 1015-26.
2. Brede, C., P. Fjeldal, I. Skjevrak, and H. Herikstad. 2003 Increased migration levels of bisphenol A from polycarbonate baby bottles after dishwashing, boiling and brushing. Food Addit Contam, v. 20(7), pp. 684-9.
3. Calafat AM, Ye X, Wong L-Y, Reidy JA, Needham LL, 2007. Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004. Environ Health Perspect, v. 116(1): doi:10.1289/ehp.10753
4. Calafat A.M., J. Weuve, X. Ye, L.T. Jia, H. Hu, S. Ringer, K. Huttner, and R. Hauser, 2009. Exposure to bisphenol A and other phenols in neonatal intensive care unit premature infants. Environ Health Perspect, v. 117, pp. 639-644.
5. Schonfelder, G., W. Wittfoht, H. Hopp, C.E. Talsness, M. Paul, and I. Chahoud, 2002. Parent bisphenol A accumulation in the human maternal-fetal-placental unit. Environ Health Perspect, v. 110(11), pp. A703-7.
6. Takeuchi, T., O. Tsutsumi, Y. Ikezuki, Y. Takai, and Y. Taketani, 2004. Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. Endocr J., v. 51, pp. 165-169.
7. Sugiura-Ogasawara, M., Y. Ozaki, S. Sonta, T. Makino, and K. Suzumori, 2005. Exposure to bisphenol A is associated with recurrent miscarriage. Hum Reprod, v. 20, pp.2325-2329.
8. Melzer, D., Rice, N.E., Lewis, C., Henley, W.E., Galloway, T.S. (2010). Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 1003/06. PLoS One, v. 5(1), pp8673.
9. Singleton, D.W., Y. Feng, Y. Chen, S.J. Busch, A.V. Lee, A. Puga, and S.A. Khan, 2004.Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol, v. 221(1-2), pp. 47-55.
10. Lee, C.K., S.H. Kim, D.H. Moon, J.H. Kim, B.C. Son, D.H. Kim, C.H. Lee, H.D. Kim, J.W. Kim, J.E. Kim, and C.U. Lee, 2005. Effects of bisphenol A on the placental function and reproduction in rats. J Prev Med Pub Health. v. 38(3), pp. 330-336.
11. Markey, C.M., P.R. Wadia, B.S. Rubin, C. Sonnenscheine, and A.M. Soto, 2005. Long Term Effects of Fetal Exposure to Low Doses of the Xenoestrogen Bisphenol-A in the Female Mouse Genital Tract. Biol Reprod, v. 72(6), pp. 1344-51.
12. Nikaido, Y., K. Yoshizawa, N. Danbara, M. Tsujita-Kyutoku, T. uri, N. Uehara, and A.Tsubura, 2004. Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring. Reprod Toxicol, v. 18(6), pp. 803-811.
13. Rubin, B.S., J.R. Lenkowski, C.M. Schaeberle, L.N. Vandenberg, P.M. Ronsheim, and A.M. Soto, 2006. Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A. Endocrinology, v.147(8), pp. 3681-3691.
14. National Toxicology Program’s Report of the Endocrine Disruptors Low Dose Peer Review (2001).
15. U.S. Department of Health and Human Services, National Institutes of Health, National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction. NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A (NIH Publication No. 08-5994).
16. Vom Saal, F.S. 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. Reproductive Toxicology, v. 24, pp. 131-138.
17. Kudakovic, M. and F.A. Champagne, 2011. Epigenetic perspective on the developmental effects of bisphenol A. Brain, Behavior, and Immunity. V. 25(6), pp. 1084-93.
18. Dolinoy, D.C., D. Huang, and R.L. Jirtle, 2007. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. PNAS, v. 104(32), pp. 13056-13061.
19. Walker, D.M. and A.C. Gore, 2011. Transgenerational neuroendocrine disruption of reproduction. Nat Rev Endocrinol. v. 7(4), pp197-207.
20. U.S. Environmental Protection Agency, 2010. Bisphenol A (BPA) action plan summary.
21. U.S. Department of Health and Human Services, 2010. Bisphenol A (BPA) information for parents.
22. Vandenberg, L.N., R. Hauser, M. Marcus, N. Olea, and W.V. Welshons, 2007. Human exposure to bisphenol A (BPA). Reproductive Toxicology, v. 24, pp. 139-177.
23. Kuo, H.W. and W.H. Ding, 2004. Trace determination of bisphenol A and phytoestrogens in infant formula powders by gas chromatography-mass spectrometery. J. Chromatogr A, v. 1027, pp. 67-74.
24. Houlihan, J., 2007. Toxic plastics chemical in infant formula. Environmental Working Group.
25. Carwile JL, Luu HT, Bassett LS, Driscoll DA, Yuan C, Chang JY, Ye X, Calafat AM, Michels KB, 2009. Polycarbonate bottle use and urinary bisphenol A concentrations. Environ Health Perspect, v. 117(9), pp. 1368-1372.
26. Vökel, Wl, Kiraoglu, M., Fromme, H., 2011. Determination of free and total bisphenol A in urine of infants. Environ Res, v. 111(1), pp.143-148.
27. Matsumoto A KN, Kitagawa K, Isse T, Oyama T, Foureman GL, Morita M, Kawamoto T. 2003. Bisphenol A levels in human urine. Environ Health Perspect 111(1): 101-4.
28. Research Center for Chemical Risk Management (2005). Bisphenol A Risk Assessment Document. AIST Risk Assessment Document Comprehensive Chemical Substance Assessment and Management Program. Japan.
29. Lyons, G.. 2000. Bisphenol A: A Known Endocrine Disruptor. WWF European Toxics Programme: Godalming, Surrey. p. 37
30. Breast Cancer Fund (2011). BPA in Kids’ Canned Food.