Bisphenol A | Breast Cancer UK

Bisphenol A

What is Bisphenol A?

Bisphenol A (BPA) is a man-made chemical first synthesised in 1891. The chemical structure of BPA shows similarity to that of Diethylstilboestrol (DES) (1), formerly used as a drug to treat women with gynaecological problems and to help prevent miscarriage and which is now classified as a group I carcinogen by the International Agency for Research on Cancer (IARC). 

BPA was identified as being an artificial oestrogen as early as 1930 (2).  Use of BPA for plastics production was not discovered until after World War One, when it was found to react with phosgene and yield a clear, hard plastic polycarbonate.

Over 3 billion kilograms of BPA are produced each year and in 2010, it was estimated to be worth around £350,000 an hour to the global economy (3).  The production of BPA has increased by 500% in the last three decades and continues to rise. 

Where is it found?

BPA is used in the manufacture of polycarbonate plastic food and drink packaging, and in epoxy resins that line some metal cans of food and drink.  BPA is also used as an additive in polyvinyl chloride (PVC) plastics. It is found in CDs, mobile phone and computer casings, glasses, dental sealants, medical devices (4) and thermal till receipts, where it's used as a colour developer.

Why should we be concerned?

BPA is able to migrate.  It can rub off onto hands, leach into food and drink contents (5) and is absorbed through the skin.

Exposure to ultraviolet light, high temperatures (such as those used in sterilisation processes), or to acidic conditions (for example, in a can of tinned tomatoes), will increase leaching.

BPA is ubiquitous.  It is found all over the planet in ecosystems and wildlife (6). It is estimated to be present in over 93% of the adult population (7) and has been found in human urine samples (8),  human serum (9), sweat (10), placental tissue (11), ovarian follicular fluid and evidence suggests it accumulates over time in human amniotic fluid (12).  It has also been found in human breast milk (13), which confirms its presence in the breast, and at even higher levels in liver, brain and human fat tissue (14).

There is sufficient evidence to suggest that dietary exposure is the main route of human exposure to BPA, along with regular contact with thermal receipt paper (15).

Whilst proponents of BPA claim that it is safe to use because human levels of exposure are low, evidence suggests that BPA is harmful even at very low levels of exposure (16, 17).   BPA gives rise to ‘non monotonic’ dose responses, which means that it has varying effects at different doses.  Therefore, the application of so-called Tolerable Daily Intakes (TDIs) (18) of BPA, which have been predicted from higher doses to permit its continued use in everyday products may well be unsafe for the consumer.  

How is BPA linked with breast cancer? 

There is a significant amount of scientific evidence that shows even low level exposure BPA has an adverse effect on the development of breast tissue. Laboratory experiments show that BPA has the ability to transform normal breast cells into cells of a more cancerous or overall malignant nature (19, 20, 21). Animal studies show that exposure to BPA in the womb, or during early life, can increase breast density, cell growth and increase susceptibility to tumours (22, 23, 24, 25, 26, 27).  BPA has also been found to trigger DNA strand breaks, to interfere with cell division (28, 29) and with chemotherapy, making it less effective against breast cancers (30).

Like DES, BPA is a synthetic oestrogen and is able to bind to oestrogen receptors both within and on the cell surface.  BPA is therefore able to influence how genes and cells behave.  Mammary tissues are primed to respond to the presence of oestrogen in order to develop and grow and, therefore, bind easily to BPA. 

Links to other diseases

As well as being linked to breast cancer, BPA is also linked to a range of other conditions including obesity (31), heart disease and cardiovascular problems (32, 33), infertility (34), diabetes (35) and recurrent miscarriage (36).

What is the current regulatory position on BPA? 

The European Commission decided to ban the use of BPA in baby bottles in March 2011 (37), because of concerns about the adverse effect of BPA on human health. It continues to be used, however, in a  wide range of other food and drinks packaging.  

France took unilateral action in December 2012 to ban the use of BPA in food and drinks packaging and in thermal receipt paper (38).  The ban, which came into force in January 2015, has since been partially overturned by the country’s courts (39). Sweden, Denmark and Belgium have also taken measures to reduce the use of BPA, in products marketed at children under three years old.

The EU will adopt a new regulation in September, 2016, which specifies a limit of 0.05mg/kg for BPA in materials that come into contact with food, "to protect human health". The current limit is 0.6mg/kg. Currently, the European Commission member state REACH Committee is considering a proposed restriction on placing on the market of thermal paper containing BPA.

The European Food Safety Authority's (EFSA) most recent review of BPA exposure and toxicity concluded that “BPA poses no health risk to consumers of any age group (including unborn children, infants and adolescents) at current exposure levels”, but acknowledged  that high levels of exposure may adversely affect the kidney, liver and mammary gland, and recommended the TDI be reduced from 50 µg/kg of bw/day to 4 µg/kg of bw/day (40). They also stated that there are "remaining uncertainties about BPA’s toxic effects" and a further re-evaluation will be carried out when the results of long-term research by the US National Toxicology Program are available for evaluation, in one or two years time. 

In February 2016, the European Commission and member states agreed to classify BPA as a category 1B presumed reproductive toxicant (41), meaning it is a substance which can adversely affect the human reproductive system. The EC Committee’s decision follows that of the state of California, which last year added BPA to its proposition 65 list of chemicals that are known to cause cancer, birth defects or other reproductive harm (42). The new EU classification is important as it lends support to a proposal by the French REACH authority to classify BPA as a substance of very high concern (SVHC), according to REACH Article 57(a) (43). Listing of a substance as an SVHC is the first step in the procedure for restriction of its use and results in more stringent regulatory measures. There would also be an obligation to implement stronger preventative measures for professional use, principally by using substitutes.

Breast Cancer UK position

Breast Cancer UK submitted evidence to EFSA's consultations on BPA, expressing concern that studies relating to low dose exposures had been dismissed (Read Breast Cancer UK's submission to Part 1 and submission to Part 2), to the European Commission's roadmap on new measures for use of BPA in food packaging material (link to submission) and to the draft opinion of the Committee for Socio-economic Analysis proposing restrictions on the use of BPA in thermal paper (link to submission).

Breast Cancer UK is calling for:

  • a ban on the use of BPA in food and drinks packaging, on the basis that studies demonstrate that low dose exposures to BPA have been shown to have an adverse effect on the developing mammary gland;
  • BPA to be prohibited from use in all articles intended to come into contact with food and drink, and that it should be replaced with safer alternatives;
  • BPA to be prohibited from use in till and other printed receipt papers;
  • BPA to be prohibited in any products intended for children under three years old, and should be replaced with safer alternatives. 

References

  1. Rubin, B.A. & Soto, A. (2009) 'Bisphenol A: Perinatal exposure and body weight' Molecular and Cellular Endocrinology 304(1-2): 55-62.
  2. Dodds E.C. and Lawson W. (2009). Synthetic estrogenic agents without the phenanthrene nucleus. Nature. 137: 996.
  3. Melzer, D. and Galloway, T. (2010). ‘Bisphenol A is everywhere – is it safe?’ New Scientist 2783: 26-27.(Link to extract)
  4. For example: auto-transfusion apparatus; filters; bypasses; tubing; pumps; instruments; surgical equipment; blood pathway circuits; and respiratory tubing circuits. These products are used on patients of all ages.
  5. Brotons, J. A., M. F. Olea-Serrano, et al. (1995). ‘Xenoestrogens released from lacquer coatings in food cans.’ Environmental Health Perspectives 103(6): 608-612.
  6. Corrales, J. et al. (2015). Global Assessment of Bisphenol A in the Environment: Review and Analysis of Its Occurrence and Bioaccumulation. Dose-Response An International Journal 13(3): 1-29.
  7.  Shankar, A., and Teppala, S. (2012). ‘Urinary Bisphenol A and Hypertension in a Multiethnic sample of US Adults.’ Journal of Environmental and Public Health 2012: 5; Shankar, A. S. et al. (2012). ‘Bisphenol A and Peripheral Arterial Disease: Results from the NHANES.’ Environmental Health Perspectives 120(9). Shankar, A., S. et al. (2012). ‘Urinary Bisphenol A Levels and Measures of Obesity: Results from the National Health and Nutrition Examination Survey 2003-2008.’ ISRN Endocrinology 2012: 965243; Shankar, A. and Teppala, S. (2011). ‘Relationship between urinary bisphenol A levels and diabetes mellitus.’ Journal of Clinical Endocrinology and Metabolism 96(12): 3822-3826.
  8. Calafat, A. M., Zsuzsanna Kuklenyik, et al. (2005). ‘Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population.’ Environmental Health Perspectives 113: 391-395.
  9. Takeuchi, T. and Tsutsumi, O. (2002). ‘Serum Bisphenol A concentrations showed gender differences, possibly linked to androgen levels.’ Biochem. Biochemical and Biophysical Research Communications 291: 76-78. (Link to Abstract)
  10. Genuis, S et al. (2012). ‘Human excretion of bisphenol A: blood, urine, and sweat (BUS) study.’ Journal of Environmental and Public Health 2012: article ID 185731.
  11. Schonfelder, G., B. Flick, et al. (2002). ‘In Utero exposure to low doses of bisphenol A lead to long term deleterious effects in the vagina.’ Neoplasia 4: 98-102.
  12. Ikezuki, Y., et al. (2002). ‘Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure.‘ Human Reproduction 17(11): 2839-2841. (Link to Abstract)
  13. Sun, Y. et al. (2004). ‘Determination of bisphenol A in human breast milk by HPLC with column-switching and fluorescence detection.’ Biomedical Chromatography 18(8): 501-507. (Link to Abstract)
  14. Fernandez, M. F. et al. (2007). ‘Bisphenol-A and chlorinated derivatives in adipose tissue of women.’ Reproductive Toxicology 24(2): 259-264. (Link to Abstract)
  15. European Food Safety Authority (2013). DRAFT Scientific Opinion on the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs – Part: exposure assessment 1:
  16. Vandenberg, L. N. et al. (2012). ‘Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses.’ Endocrine Reviews 33(3): 378-455.(Link to Abstract).
  17. Jenkins, S. et al. (2011). ‘Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in mammary carcinogenesis and metastasis in MMTV-erbB2 mice.’ Environmental Health Perspectives 119(11): 1604-1609.
  18. TDI is an estimate of the amount of a substance expressed on a body weight basis, which can be ingested daily over a lifetime without appreciable risk. 
  19. Fernandez, M. F. et al. (2007). ‘Bisphenol-A and chlorinated derivatives in adipose tissue of women.’ Reproductive Toxicology 24(2): 259-264. (Link to Abstract)
  20. Fernandez, S, V. et al. (2012). 'Expression and DNA methylation changes in human breast epithelial cells after bisphenol A (BPA) exposure.' International Journal of Oncology 41(1): 369–377.
  21. Goodson, W. H. et al. (2011). ‘Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women.’ Carcinogenesis 32(11): 1724-1733.
  22. Tharp, A. P. et al. (2012). ‘Bisphenol A alters the development of the rhesus monkey mammary gland.’ Proceedings of the National Academy of Sciences USA 109(21): 8190-8195.
  23. Jenkins, S. et al. (2012). 'Endocrine-active chemicals in mammary cancer causation and prevention.' Journal of Steroid Biochemistry and Molecular Biology.129(3-5): 191-200.
  24. Durando, M. et al. (2011). 'Prenatal exposure to bisphenol A promotes angiogenesis and alters steroid-mediated responses in the mammary glands of cycling rats.' Journal of Steroid Biochemistry and Molecular Biology 127(1-2):35-43. (Link to Abstract)
  25. Markey, C. M. et al. (2001). ‘In Utero Exposure to Bisphenol A Alters the Development and Tissue Organization of the Mouse Mammary Gland.’ Biology of Reproduction 65(4): 1215-1223.
  26. Soto, A. M. et al. (2008). ‘Does breast cancer start in the womb?’ Basic and Clinical Pharmacology and Toxicology 102(2): 125-133.
  27. Jenkins, S. et al. (2011). ‘Chronic oral exposure to bisphenol A results in a nonmonotonic dose response in mammary carcinogenesis and metastasis in MMTV-erbB2 mice.’ Environmental Health Perspectives 119(11): 1604-1609; Jenkins, S. et al. (2012). 'Endocrine-active chemicals in mammary cancer causation and prevention.' Journal of Steroid Biochemistry and Molecular Biology 129(3-5):191-200.
  28. Iso, T. et al. (2006). ‘DNA damage caused by bisphenol A and estradiol through estrogenic activity.’ Biological and Pharmaceutical Bulletin 29(2): 206-210. (Link to Abstract)
  29. George, O. et al. (2008). ‘Bisphenol A directly targets tubulin to disrupt spindle organisation in embryonic and somatic cells.’ ASC Chemical Biology 3(3):167-79.
  30. LaPensee, E. W. et al. (2010). ‘Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells.’ Cancer Letters 290(2): 167-173.
  31. Shankar, A., and Teppala, S. (2012). ‘Urinary Bisphenol A and Hypertension in a Multiethnic sample of US Adults.’ Journal of Environmental and Public Health 2012:(5).
  32. Melzer, D. et al. (2012). ‘Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women.’ Circulation 125(12): 1482-1490.
  33. Shankar, A. et al. (2012). ‘Bisphenol A and Peripheral Arterial Disease: Results from the NHANES.’ Environmental Health Perspectives 120(9).
  34. Salian, S. et al. (2011). ‘Perinatal exposure of rats to Bisphenol A affects fertility of male offspring--an overview.’ Reproductive Toxicology 3: 359-362. (Link to Abstract)
  35. Shankar, A. et al. (2011). ‘Relationship between urinary bisphenol A levels and diabetes mellitus.’ Journal of Clinical Endocrinology and Metabolism 96(12): 3822-3826.
  36. Sugiura-Ogasawara, M. et al. (2005). ‘Exposure to bisphenol A is associated with recurrent miscarriage.’ Human Reproduction 20(8): 2325-2329. (link to abstract)
  37. European Commission (2011) ‘Ban of Bisphenol A in baby bottles’. Health & Consumer Voice March 2011 Edition. (accessed March 29, 2016)
  38. The French law can be read here
  39. Robert, A. (2015). France overturns ban on BPA in export products. EurActive France; published September 30, 2015. (accessed March 29, 2016).
  40. EFSA (2015). European Food Safety Authority. No consumer health risk from bisphenol A exposure' exposure. January 21 press release. (accessed March 29, 2016)
  41. ENDs Europe (2016). BPA toxicity classification strengthened. (accessed March 29, 2016).
  42. OEHHA (2015). Changes to Proposition 65 list. Bisphenol A listed as known to the State of California to cause Reproductive toxicity. Effective May 11, 2015. (accessed March 29, 2016).
  43. ECHA (2016). European Chemicals Agency. Current SVHC intentions. (accessed March 29, 2016)

 


Page last updated 21 October 2016
 

Did you find this article useful?

1 2 3 4 5
This entry has not been rated yet.

Help us prevent breast cancer Make a donation now