Fact-checking the Bisphenol-A (BPA) Story
Hat tip to Pat for starting the thread on BPA and to Jon for finding the detailed related Citizen article. It is a great issue to track the progress of because the answer is not obvious, the science is evolving and the topic is emotionally charged. Public discussion of it will likely draw out extreme views by anti-toxin heath/environmental advocates on one side and pro-business/chemical industry supporters on the other side. Such an ideologically prone discussion will require careful and critical analysis of the data and claims.
Out of interest, I searched the PubMed database for “bisphenol A” and found 225 journal articles from 1960 to the present.
(Keep in mind, that the following is just a layman’s analysis, and that the published articles have been taken at face value.) It is interesting that, as early as the 1960s, there were titles like “Sensitivity to bisphenol A” (Gaul, LE. Arch Dermatol. 1960 Dec;82:1003) and “Metabolism of bisphenol A in the rat” (Knaak JB, Sullivan LJ. Toxicol Appl Pharmacol. 1966 Mar;8(2):175-84). Unfortunately, the articles and abstracts for these sources are not online to see what their findings were back then.
Much of what the Citizen article said checks out. Many BPA-related articles have observed the detrimental effects of BPA as an estrogenic compound in animal and tissue studies. As well, a number of articles surveyed the environmental levels of BPA in water systems, sewage effluent and landfill ooze (they called it “leachate”), but the consensus view articulated is that the greatest exposure mechanism for humans is, in fact, leaching from polycarbonate bottle and food containers.
Over time, there does seem to be a changing view of the risks of BPA to human health, but it is not entirely clear in the article trail whether this really reflects new findings, changing attitudes or influence from interest groups. My inexpert analysis based on my review is that scientific evidence is building, although conclusions cannot be indisputably made yet. An example of this change in view can be seen by comparing these two fairly recent articles:
Kamrin MA. “Bisphenol A: a scientific evaluation.” MedGenMed. 2004 Sep 3;6(3):7.
“Comparing these acceptable intakes with the best exposure estimates reveals that human doses of BPA from migration of the compound into food and drink are orders of magnitude lower than acceptable daily intakes. Thus, it is very unlikely that humans, including infants and young children, are at risk from the presence of BPA in consumer products.”
Bradley EL, Read WA, Castle L. “Investigation into the migration potential of coating materials from cookware products.” Food Addit Contam. 2007 Mar;24(3):326-35.
“Potential consumer exposure was calculated. None of the substances identified had the potential to exceed their tolerable daily intake (TDI) value. To confirm these worst-case calculations, the migration of certain phthalates and of bisphenol A was measured into food simulants. Migration levels were very low.”
to these even more recent ones:
Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV. “Human exposure to bisphenol A (BPA).” Reprod Toxicol. 2007 Aug-Sep;24(2):139-77.
“We have reviewed the few epidemiological studies available that explore biological markers of BPA exposure and human health outcomes. We have examined several studies of levels of BPA released from consumer products as well as the levels measured in wastewater, drinking water, air and dust. Lastly, we have reviewed acute metabolic studies and the information available about BPA metabolism in animal models. The reported levels of BPA in human fluids are higher than the BPA concentrations reported to stimulate molecular endpoints in vitro and appear to be within an order of magnitude of the levels needed to induce effects in animal models.”
Le HH, Carlson EM, Chua JP, Belcher SM. “Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons.” Toxicol Lett. 2008 Jan 30;176(2):149-56.
“To test the hypothesis that bioactive BPA was released from polycarbonate bottles used for consumption of water and other beverages, we evaluated whether BPA migrated into water stored in new or used high-quality polycarbonate bottles used by consumers. Using a sensitive and quantitative competitive enzyme-linked immunosorbent assay, BPA was found to migrate from polycarbonate water bottles at rates ranging from 0.20ng/h to 0.79ng/h. At room temperature the migration of BPA was independent of whether or not the bottle had been previously used. Exposure to boiling water (100 degrees C) increased the rate of BPA migration by up to 55-fold. The estrogenic bioactivity of the BPA-like immunoreactivity released into the water samples was confirmed using an in vitro assay of rapid estrogen signaling and neurotoxicity in developing cerebellar neurons. The amounts of BPA found to migrate from polycarbonate drinking bottles should be considered as a contributing source to the total “[endocrine disrupting chemical] EDC-burden” to which some individuals are exposed.”
Although there continues to be a debate:
Kamrin MA. “The ‘low dose’ hypothesis: validity and implications for human risk.” Int J Toxicol. 2007 Jan-Feb;26(1):13-23.
“In the late 1990s, a “low dose” hypothesis was proposed based on studies that purported to show that hormonally active environmental agents were causing a variety of effects, mainly reproductive and developmental, at “low doses.” The supporters of this hypothesis claim that traditional “high-dose” toxicity studies are not adequate to assess adverse effects from these hormonally active agents in that they do not detect effects that are occurring at “low doses.” In addition, it is claimed that these “low dose” effects are occurring at levels comparable to those to which humans are being exposed. These claims have been controversial and expert panels evaluated the evidence behind them in the early 2000s. Although these panels generally concluded that such “low dose” effects were not conclusively established, proponents of the “low dose” hypothesis assert that a large number of more recent studies now provide clear support for their hypothesis. This review carefully examines both recent and older studies that have been cited to support the “low dose” hypothesis, including their relevance for the human population. These include in vivo and in vitro laboratory studies as well as a very limited number of epidemiological investigations. Based on the evidence, it is concluded that these “low dose” effects have yet to be established, that the studies purported to support these cannot be validly extrapolated to humans, and the doses at which the studies have been performed are significantly higher than the levels to which humans are exposed.”
Nevertheless, the entire Aug-Sep volume of Reproductive Toxicology is devoted to BPA and includes the Chapel Hill BPA expert panel consensus report discussed in the Citizen article:
vom Saal FS, Akingbemi BT, Belcher SM, et al. “Chapel Hill bisphenol A expert pane
l consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure.” Reprod Toxicol. 2007 Aug-Sep;24(2):131-8.
“The published scientific literature on human and animal exposure to low doses of BPA in relation to in vitro mechanistic studies reveals that human exposure to BPA is within the range that is predicted to be biologically active in over 95% of people sampled. The wide range of adverse effects of low dose BPA in laboratory animals exposed both during development and in adulthood is a great cause for concern with regard to the potential for similar adverse effects in humans. Recent trends in human diseases relate to adverse effects observed in experimental animals exposed to low doses of BPA. Specific examples include: the increase in prostate and breast cancer, uro-genital abnormalities in male babies, a decline in semen quality in men, early onset of puberty in girls, metabolic disorders including insulin resistant (type 2) diabetes and obesity, and neurobehavioral problems such as attention deficit hyperactivity disorder (ADHD).
There is extensive evidence that outcomes may not become apparent until long after BPA exposure during development has occurred. The issue of a very long latency for effects in utero to be observed is referred to as the developmental origins of adult health and disease (DOHaD) hypothesis. These developmental effects are irreversible and can occur due to low-dose exposure during brief sensitive periods in development, even though no BPA may be detected when the damage or disease is expressed. However, this does not diminish our concern for adult exposure, where many adverse outcomes are observed while exposure is occurring. Concern regarding exposure throughout life is based on evidence that there is a chronic, low level exposure of virtually everyone in developed countries to BPA. These findings indicate that acute studies in animals, particularly traditional toxicological studies that only involve the use of high doses of BPA, do not reflect the situation in humans.
The fact that very few epidemiological studies have been conducted to address the issue of the potential for BPA to impact human health is a concern, and more research is clearly needed. This also applies to wildlife, both aquatic and terrestrial. The formulation of hypotheses for the epidemiological and ecologists studies can be greatly facilitated by the extensive evidence from laboratory animal studies, particularly when common mechanisms that could plausibly mediate the responses are known to be very similar in the laboratory animal models, wildlife and humans.”
This concluding section of the report is useful as a caution and as an endorsement for further research, but it is far from a declaration. The observations are very speculative. BPA exposure is everywhere, developmental effects may take years to indicate, and some of the current disease trends in humans happen to be the same as the experimental effects in exposed laboratory animals. Those sound like excellent grounds for a hypothesis but not a conclusion.
The move to epidemiological studies seems to be the next logical step, but if “there is a chronic, low level exposure of virtually everyone in developed countries to BPA” (see above), then where is the control group? Regardless, some studies are laying the groundwork. For example:
Dekant W, Völkel W. “Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures.” Toxicol Appl Pharmacol. 2007 Dec 14.
“Human exposure to bisphenol A is controversially discussed. This review critically assesses methods for biomonitoring of bisphenol A exposures and reported concentrations of bisphenol A in blood and urine of non-occupationally (“environmentally”) exposed humans.”
Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. “Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004.” Environ Health Perspect. 2008 Jan;116(1):39-44.
“Urine concentrations of total BPA differed by race/ethnicity, age, sex, and household income. These first U.S. population representative concentration data for urinary BPA and tOP should help guide public health research priorities, including studies of exposure pathways, potential health effects, and risk assessment.”
For a more qualified review of the issue, a couple of articles on the Public Library of Science (PLoS) site cover this topic well:
Quitmeyer A, Roberts R. “Babies, Bottles, and Bisphenol A: The Story of a Scientist-Mother.” PLoS Biol. 2007 July; 5(7): e200.
Hawley RS, Warburton D. “Scrambling eggs in plastic bottles.” PLoS Genet. 2007 Jan;3(1):e6.
It will be interesting to see how this issue develops – rationally or emotionally – as more comprehensive studies and policy reviews (hat tip: Halden) are anticipated this year:
“Health Canada is aware of the concerns surrounding bisphenol A. … We are currently finalizing our studies on bisphenol A leaching from baby bottles as well as [our] review of the risks posed from bisphenol A and expect to publish the results of our review no later than May, 2008.”