Chemicals from a bottle: Bisphenol-A

Bisphenol-A (BPA) made headlines late in 2007 when Mountain Equipment Co-op (MEC) suspended sales of bottles made using the chemical. MEC cited growing consumer concern that BPA may leach from polycarbonate bottles (1). In the last six months retailers such as Walmart, Lululemon and Canadian Tire have all pulled or stopped stocking selected BPA-containing products, and regulatory bodies have re-evaluated their safety.

Katja Gorup, plastic, 2008
Certains droits réservés.

Bisphenol-A (BPA) had already been shown to imitate hormones, but many thought environmental BPA exposure too low to induce disruptive effects. If the amount of science pooled towards BPA in the last year is any indication of its current importance, then it ranks as one of the highest-concern chemicals. Between April 2007 and April 2008, nearly 400 articles related to the effects of BPA on our health or on the environment were published. This staggering amount of research makes a thorough review of the topic difficult, and many papers expand the range of health effects BPA may have, without determining if the effects are biologically relevant. The keystone of any scientific consensus would be a large, well-designed human study linking environmental exposure to BPA to a significant health problem, but this has yet to be carried out. More recent articles, however, point to an even wider range of potential health risks associated with BPA.

What is BPA?BPA was first described over 100 years ago, and it is made by condensing acetone and phenol, with an acid catalyst. Acetone is a common solvent, known for its use as nail polish remover. Phenol is a common aromatic chemical used in plastics and pharmaceuticals. For over 50 years BPA has been used for many plastics applications, although recently it has been mostly used for polycarbonate synthesis and epoxy resins.

Polycarbonate plastic is a tough, versatile material and can be manufactured as appealing transparent, lightweight and non-staining containers. Compact discs, protective lens-wear and sports gear, laboratory equipment and reusable drinking bottles are some of the more common items made of this plastic. Epoxy resins are used to line most cans, aiding in the preservation of foods and beverages, and also in the linings of water supply pipelines.

Plastics derived from BPA are undoubtedly useful, and because of their usefulness and adaptability, they are ubiquitous. Exposure to BPA is therefore ubiquitous as well.

The daily amount of human exposure to BPA is typically very small and comes mostly from diet, as it leaches from plastic bottles and canned food. Questions about the effects of BPA on human and mammalian health revolve around the effect of low daily doses.

BPA ExposureHow much BPA are you exposed to everyday? In absolute amounts, very little – micrograms per kilogram of bodyweight each day. But low-level exposure is the relevant measure for potential health effects of BPA. The National Toxicology Program has compiled tables of both the possible ingested BPA and excreted BPA from known human studies and other estimates (2). (Table 1.)

Both the United States Environmental Protection Agency and the European Food Safety Authority have established a tolerable daily intake of 50µg/kg/day.

Reported Health EffectsAs mentioned, BPA does not have high acute toxicity when exposure to the chemical is limited. Studies in rodents, using amounts of BPA far in excess of what is possible through human diet, show the chemical does have severe effects on birthrate, survival, development and onset of puberty. Although high-doses of BPA are undoubtedly a health hazard, the BPA controversy concerns low-dose effects. Do dietary intakes of BPA pose a significant health risk?

Several limitations in the field of BPA science have made it difficult to draw a definite conclusion about the effects of exposure to low amounts of BPA. Given that many regulatory bodies give no greater weighting to independent studies than to industry-sponsored research, the real health costs of low-level BPA exposure is sometimes hard to estimate. However the research used by some plastic industry lobbyists to defend BPA has in some instances been superseded by more recent and contradictory research. The lack of human studies on the effects of low doses of BPA also forces authorities to draw conclusions from animal studies. Although this is a long accepted practise, lobbying from either side of these decisions regularly demand more conclusive research be done using data from humans. Some of the experimental design has been questioned, particularly in regards to the unknown long-term effects of low-level BPA on fetal and pubertal animals, and the route of administration of BPA.

Conclusive environmental effects were discovered at a laboratory led by Patricia Hunt and Terry Hassold, experts in chromosomal errors. Workers in their laboratory routinely used harsh chemical cleaners on polycarbonate mouse cages and water bottles. Chromosomal errors in dividing cells increased from 2% to 40%. In 2003 the laboratory published a study showing that the accidental exposure to BPA liberated from damaged equipment had caused the marked increase (3), and that by changing the cleaning methods the effect was mitigated.

In January 2008 the mechanism by which BPA binds and disrupts estrogen-related receptors was described (4). The particular receptor which was used in the study is expressed strongly in developing mammalian brain tissue. The downstream consequences of the disruption caused by BPA are yet to be described, as the specific function of the receptor in the study is not known. Nonetheless, disruption to a receptor that is expressed in developing brain tissue, and that interacts with estrogen, critical for sexual differentiation and development, is good cause for concern. Studies have suggested that BPA may alter sexual differentiation in the brains of rats (5), leading to changes in gender-related behaviour, at doses around 20µg/kg/day, and as low as 0.025µg/kg/day (6). Other brain-related effects may include changes at dopamine receptors (7) important for motivation and motor control, and studies have reported possible effects on neuronal cell death and the mechanisms of learning and memory.

There is additional evidence that urinary tract development and mammary tissue may be affected by exposure to BPA (8). Other putative effects, such as a link between BPA and obesity, are still speculative, though exposure to BPA does increase fatty tissue and cholesterol in mice (9).

BPA also seems to pose extra risk to fetal, newborn and infant development, as the metabolic processing of BPA in early life is less efficient. Adults are more able to metabolize toxins such as BPA from the bloodstream, and the exposure per kilogram of bodyweight is much lower.

Chemical Controversies and RegulationsSince MEC took action to remove the potentially harmful bottles, other studies of chemical leaching have also made headlines, perhaps most notably the one entitled “Volatile Vinyl: The New Shower Curtain’s Chemical Smell” (10). This report claims that many volatile organic compounds from PVC shower curtains may be a health risk, as are small amounts of compounds already known to be a risk. But there is something of a renewal of interest in chemical exposure and pollution in North America. Activists have capitalized on their success at drawing attention to visible chemical pollution and its health effects, environmental pollution and the thousands of chemicals people are exposed to from everyday items.

In lieu of definitive evidence linking BPA to human health effects, governments worldwide are beginning to apply precautionary approaches to the handling of BPA. On April 18 this year, the Canadian government designated bisphenol-A “toxic to human health” as part of Canada’s Chemical Management Plan. Canada is now poised to become the first country to significantly limit the use of BPA. In his speech announcing the move (11), Health Minister Tony Clement noted that polycarbonate baby bottles would be banned, and that funding from the Chemical Management Plan would be dedicated to research and assisting industry. No other national or regional governments have announced a similar ban, although some cities in the US have announced symbolic bans.

The next decade will see a huge increase in chemical assessments as governments respond to the 2006 Strategic Approach to International Chemical Management (SAICM) (12). The broad goal of the SAICM is to ensure that by 2020 chemicals are produced and used in ways that reduce health and environmental impacts. If this goal is to be realized, then the way chemicals such as BPA are handled and assessed by regulators will drastically change as well. This may restrict the use of chemicals, but it will also create an opportunity to innovate safe alternatives.

Advice for Handling BPABecause BPA seems to pose risk mostly to infants, polycarbonate feeding bottles and cans of infant formula lined with BPA-plastics are the likely riskiest sources. Simple steps can be taken to reduce BPA-leakage from feeding bottles, mostly by keeping liquids at low temperatures and taking care not to overheat or damage the plastic during cleaning. Infant formula is a more controversial source, because of the use of epoxy resins in container linings. While the heating process used in preserving cans of formula may aid migration of BPA into the powder, the nutritional benefits of infant formula outweigh that risk in the minds of regulators. Health Canada has recommended that consumers do not change their diet based on the presence of BPA in canned goods, as the amounts leaching into canned foods are in the low parts per billion. There may need to be innovations in the packaging used for infant formulas, or a change to non-BPA alternatives. Breast-feeding may also reduce BPA exposure, although there are no reliable studies into the amount of BPA transferred by breast-milk.

As Canada seems likely to be the first country to ban any BPA plastics, it does so with active consent from retailers and consumers. Because a watertight scientific consensus has not emerged, it is critical that the precautionary principle is applied and these products are removed or diminished in the community. The risks do not apply evenly; they overwhelmingly affect the unborn, infants and youth, a group not usually empowered to decide how much of a particular chemical they would like to ingest. If BPA is conclusively shown to be a risk, then to remove it now would show fortunate insight. If no harm can be proven, then it will be seen as a small price to pay in the name of health and safety.

Meanwhile BPA will remain part of the environment for many years to come. It is extremely unlikely that all polycarbonate plastics will need to be removed from society, as many pose no ingestion risk. Polycarbonate plastics will continue to be a useful and lucrative material for the foreseeable future. Losing baby bottles and can linings from the list of uses for polycarbonate plastic is a reasonable compromise.

Health Canada has guidelines for handling polycarbonate bottles, as well as details about the Chemical Management Plan, on-line at www.chemicalsubstanceschimiques.gc.ca

References

(1) Mountain Equipment Co-op, http://www.mec.ca/Main/content_text.jsp?FOLDER%3C%3Efolder_id=2534374302881801&CONTENT%3C%3Ecnt_id=10134198674101533 (2008)
(2) Draft NTP Brief on Bisphenol-A, April 14 2008. Available at http://cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pdf
(3) Hunt, P.A., K.E. Koehler, M. Susiarjo, C.A. Hodges, A. Ilagan, R.C. Voigt, S. Thomas, B.F. Thomas, and T.J. Hassold. “Bisphenol a exposure causes meiotic aneuploidy in the female mouse.” Current Biology 13.7 (2003): 546-53.
(4) Okada, Hiroyuki, Takatoshi Tokunaga, Xiaohui Liu, Sayaka Takayanagi, Ayami Matsushima, and Yasuyuki Shimohigashi. “Direct Evidence Revealing Structural Elements Essential for the High Binding Ability of Bisphenol A to Human Estrogen-Related Receptor-?”. Environmental Health Perspectives 116.1 (2008): 32–38.
(5) Kubo, K., O. Arai, M. Omura, R. Watanabe, R. Ogata, and S. Aou. “Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats.” Neurosciences Research 45.3 (2003):345-56.
(6) Rubin, Beverly S., Jenny R. Lenkowski, Cheryl M.Schaeberle, Laura N. Vandenberg, Paul M. Ronsheim, and Ana M. Soto. “Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A.” Endocrinology 147.8 (2006): 3681-3691
(7) Suzuki T., K. Mizuo, H. Nakazawa, Y. Funae, S. Fushiki, S. Fukushima, T. Shirai, and M. Narita. “Prenatal and neonatal exposure to bisphenol-A enhances the central dopamine D1 receptor-mediated action in mice: enhancement of the methamphetamine-induced abuse state.” Neuroscience 117.3 (2003): 639-644.
(8) Timms, BG., K.L. Howdeshell, L. Barton, S. Bradley, C.A. Richter, and F.S. vom Saal. “Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra.” Proceedings of the National Academy of Science 102.19 (2005): 7014-7019
(9) Miyawaki, Joji, Kenshi Sakayama, Hideo Kato, Haruyasu Yamamoto and Hiroshi Masuno. “Perinatal and Postnatal Exposure to Bisphenol A Increases Adipose Tissue Mass and Serum Cholesterol Level in Mice” Journal of Atherosclerosis and Thrombosis 14.5 (2007): 245-252.
(10) Lester, Stephen, Michael Schade, and Caitlin Weigand. “Volatile Vinyl”. June 2008. Center for Health, Environment and Justice. June 15th 2008. http://www.toxicnation.ca/files/toxicnation/report/VolatileVinylReport.pdf
(11) “Minister’s remarks on Bisphenol-A”. April 2008. Health Canada. June 15th 2008. http://www.hc-sc.gc.ca/ahc-asc/minist/speeches-discours/2008_04_18-eng.php
(12) “Strategic Approach to International Chemical Management”, http://www.chem.unep.ch/saicm/