Environmental Medicine Update

by Marianne Marchese, ND

Breast Cancer and Bisphenol A

Introduction

Bisphenol A (BPA) is a chemical used in the manufacture of polycarbonate plastic, a type of plastic used for baby bottles and water bottles. It is used in the plastic lining of metal food cans, dental sealants, and the carbonless paper receipts that most cashiers hand out after a purchase at the store.¹ Most people in the US are exposed to BPA daily, whether they know it or not. It is estimated that as many as 90% of the US population has detectable levels of BPA in the bloodstream.² BPA has estrogenlike effects in the body and is considered an estrogen-mimicking chemical with links to breast cancer.

What is Bisphenol A?

Bisphenol A was developed in 1891 and recognized as a synthetic estrogen in the 1930s. In the 1950s, it was discovered that it could be used to make two kinds of plastics: polycarbonate and epoxy resins.³ BPA-based polycarbonates are used in products such as baby bottles, water bottles, medical equipment, toys, CDs/DVDs, cell phones, and consumer electronics. Epoxy resins containing BPA are used as liners for most food and beverage cans, adhesives, industrial protective coatings, and automotive primers. BPA is also used to make dental sealants and flame retardants.³ BPA can leach from plastics into food and water, creating an unsuspected source of exposure. Heating of cans to sterilize food, the presence of acidic food or beverages in cans or polycarbonate plastic bottles, and repeated washing of polycarbonate products have all been shown to increase the rate of leaching of BPA.⁴ In November 2008, the Journal Sentinel published a study that it performed on 10 products for infants billed as microwave safe. The Journal Sentinel found that heating the plastic containers in an oven or microwave caused BPA to leach.⁵ More important, it found that BPA leached from plastic containers with the recycling numbers 1,2,5, and 7 – in the past, it was thought only plastic containers with the number 7 on the bottom leached BPA. This leaching means that people are exposed through food and water; such exposure can build up in the body over time.

Most people in the US have detectable levels of BPA in their bodies. The Centers for Disease Control and Prevention (CDC) recently released the Fourth National Report on Human Exposure to Environmental Chemicals. CDC scientists measured BPA in the urine of 2517 participants aged 6 years and older who took part in the agency’s National Health and Nutrition Examination Survey (NHANES) during 2003–2004. (See www.cdc.gov/nchs/nhanes.htm.) They found BPA in the urine of nearly all the people tested, which indicates widespread exposure in the US population. In this study, the 95th percentile value of BPA concentrations was 8.3 μg/g creatinine. The ratio of the 95th percentile to 50th percentile of BPA concentrations for women ages 16 to 49 years was 3.6, indicating that BPA concentrations in the most exposed members of the population were nearly four times greater than the population median. But do these levels in the body cause adverse health effects?

Health Effects of Bisphenol A

The Endocrine Disruption Exchange (TEDX) recently published a scientific review summarizing studies looking at the effects of BPA at levels of 1 ppb (1 mg/kg/day) or less. This level is considered low-dose exposure. The Environmental Protection Agency (EPA) has set the lowest observed adverse effect level (LOAEL) for BPA at 50mg/kg/day. TEDX chose to review studies on the health effects of BPA at 1 ppb or less, a level well below the EPA’s LOAEL. The results of this study showed that low-dose exposure to BPA is linked to changes in the testes, penis, prostate, and sperm function. In females, BPA was shown to affect the development of eggs, embryos, and breast tissue. BPA altered the organization and functioning of brain tissue and the behavior of animals. Exposure to BPA was correlated with polycystic ovarian syndrome, an increase in miscarriages, and a decrease in successful births. BPA can change pancreatic function and is linked with diabetes and cardiovascular disease. These are only a few of the health effects linked to low-dose BPA exposure. TEDX’s full report on BPA can be viewed at www.endocrinedisruption.com/endocrine.TEDXList.overview.php.

Hormones and Bisphenol A

One of the ways that BPA affects human health is by altering hormones in the body. BPA has been reported to cause thyroid hormone disruption, alter follicle stimulating hormone, and increase total testosterone.⁶ It is also known to affect estrogen in the body, acting as an estrogen mimicker and possessing estrogenlike properties. BPA is often described as a weak estrogen because the dose needed to stimulate breast–cancer cell growth is 100,000 times higher than estradiol, the main estrogen receptor found on breast cancer cells.⁴ However, BPA has been shown to alter cell function and prolactin secretion at very low doses, less than 1 part per trillion.⁴ Despite BPA’s having lower estrogenicity than estradiol, in in vivo studies its estrogenicity is only 100-fold lower than that of diethylstilbesterol (DES).⁷ A study comparing the estrogenicity of BPA and DES found that when a mouse was exposed in utero to both, it had higher risk of breast cancer as an adult.⁸ Even though BPA is a weak estrogen, it can have estrogenlike effects similar to those of DES. A recent animal study showed that the active metabolite of BPA called 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene (MBP) is more estrogenic than its parent BPA.⁹ The estrogenicity of MBP metabolite appeared to be severalfold to several thousandfold stronger than that of BPA. BPA is metabolized in the liver by the CYP450 enzymes, and methylation and glucuronidation. It is postulated that when the detoxification pathways of the liver don’t work efficiently, then perhaps the more estrogenic metabolite of BPA is formed.⁹ Many factors account for the hormone-disrupting effects of BPA in animals, humans, and cell lines. Numerous studies have documented the links to specific health conditions. Given the estrogenicity of BPA, it is important to consider its links to breast cancer.

Breast Cancer and Bisphenol

A

In 2010 the Breast Cancer Fund, a nonprofit group that looks at the scientific evidence linking chemical exposure to breast cancer, released a report called State of the Evidence. This report summarizes the scientific studies on radiation and chemicals in the environment and their links to breast cancer. In regard to BPA exposure, the report cites concerns for the development of breast cancer. Here is a summary of BPA links to breast cancer. The full report can be read at online.¹⁰

1. Several studies using both rat and mouse models have demonstrated that even brief exposures to BPA during gestation or around the time of birth lead to changes in mammary tissue predictive of later development of breast tumors (Maffini 2006; Markey 2001; Muñoz-de-Toro 2005).

2. Prenatal exposure of rats to BPA results in increases in the number of precancerous lesions and in situ tumors (carcinomas; Murray 2007a), as well as increased number of mammary tumors following adulthood exposures to low doses (Durando 2007; Jenkins 2009).

3. Studies using cultures of human breast cancer cells demonstrate that BPA acts through the same response pathways as the natural estrogen estradiol (Rivas 2002; Welshons 2006). BPA can interact weakly with the intracellular estrogen receptor (ER), and it can also alter breast cell responsiveness.

4. BPA has been shown to mimic estradiol in causing direct damage to the DNA of

cultured human breast cancer cells (Iso 2006).

As the evidence grows linking BPA to breast cancer, so does the evidence that BPA can interfere with chemotherapy treatment for breast cancer. A 2009 study showed that low-dose BPA can reduce the efficacy of chemotherapy agents in women with estrogen receptor positive and negative breast cancer.¹¹ This is specifically pronounced with the chemo agent cisplatin. BPA antagonizes cisplatin toxicity, offers resistance against cisplatin, thereby preventing drug-induced apoptosis of breast cancer cells.¹²

Is There an Alternative?

As evidence mounts showing adverse health effects of BPA, the call to remove this chemical from consumer products grows. Environmental groups, activists, physicians, and consumers are increasing the pressure on the government to begin to regulate BPA. Some states are taking matters into their own hands. Maine had already banned BPA use in food and beverage containers, and Oregon is considering a similar ban. Some manufactures are taking the initiative to create BPA-free bottles to stay a step ahead of the regulation. But what are they using instead of BPA? According to a New York Times article, BPA-free bottles contain bisphenol S (BPS).¹³ The article points out that the few tests conducted outside the US on BPS show that it has estrogenic activity – not as strong as that of BPA, but not a good sign. BPS is now used in the US to make polyethersulfone (PES) plastic. Some baby bottles marketed as BPA free use PES plastic. Although it is a good thing that manufacturers are pulling BPA out of bottles, they are not doing the proper testing on the chemicals replacing BPA. The system is broken. We must reverse the process: test first; then, and only then, should we allow only chemicals proven to be safe into consumer products.

Summary

Concerns about BPA have lingered for years. BPA is present in numerous household products such as canned foods, plastic containers and bottles, dental sealants, carbonless paper sales receipts, and more. It is almost impossible to avoid, even if you try, and it is present in the blood and urine of over 90% of the US population. BPA has known estrogenic effects in animals, cell cultures, and humans. More and more scientific studies are clearly making the connection to low-dose BPA and breast cancer risk. Avoiding the use of plastic bottles, canned food, and plastic food containers is a good start in reducing exposure to BPA. Getting this chemical and other estrogen-mimicking chemicals out of consumer products is the only way to truly eliminate exposure and stop the adverse health effects in humans.

Notes

1. vom Saal FS, Myers JP. Bisphenol A and risk of metabolic disorders. JAMA. 2008;300:1353–1355.

2. Lang IA, et al. Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008;300:1303–1310.

3. Steinmetz R et al. The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. Endocrinology. 1997;138(5):1780–1786.

4. vom Saal FS, Hughes C. An extensive new literature concerning low-dose effects of bisphenol-A shows the need for a new risk assessment. Environ Health Perspect. 2005;113(8):926–933.

5. Rust S, Kissinger M. BPA leaches from “safe” products. Journal Sentinel. Nov 15 2008. Available at: http://www.jsonline.com/watchdog/watchdogreports/34532034.html. Accessed May 19 2011.

6. Galloway T et al. Daily Bisphenol-A excretion and associations with sex hormone concentration: a result from the InCHIANTI Adult Population Study. Environ Health Perspect. 2010:118(11):1603–1608.

7. Nagel SC, et al. Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vitro bioactivity of the xenobiotic estrogens bisphenol A and 4-octylphenol. Environ Health Perspect. 1997;105:70–76.

8. Bromer JG et al. Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. FASEB J. 2010;24(7):2273–2280.

9. Yoshihara S et al. Potent estrogenic metabolites of bisphenol A and bisphenol B formed by rat liver S9 fraction: their structures and estrogenic potency. Toxicol Sci. 2004;78(1):50–59.

10. Grey J. State of the Evidence: the Connection Between Breast Cancer and the Environment. 6th ed. 2010. Available at: www.breastcancerfund.org/media/publications/state-of-the-evidence. Accessed May 20, 2011.

11. LaPensee EW et al. Bisphenol-A at low nanomolar doses confers chemoresistance in estrogen receptor-α-positive and negative breast cancer cells. Environ Health Perspect. 2009;117(2):175–180.

12. LaPensee EW et al. Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells. Cancer Lett. 2010;290(2):167–173.

13. Browning D. Hitting the bottle. New York Times. Epub May 8, 2011. www.nytimes.com/2011/05/09/opinion/09browning.html?_r=1&hp.