Are the FDA's recent claims about BPA accurate?
In this article, I am going to examine a topic that has recently faced significant controversy:
The detrimental effects of a chemical known as bisphenol A, also known as BPA.
BPA is considered an endocrine disrupting chemical (EDC), and is commonly found in plastic products, such as food packaging, beverage bottles, and toys. A growing number of studies have identified BPA as having detrimental effects on the body at low doses, especially during development.
However, the conclusions of a recent large collaborative project that measured the effects of BPA called CLARITY (Consortium Linking Academic and Regulatory Insights on Toxicity of BPA) revealed, at first glance, quite the opposite.
The CLARITY consortium is a collaborative research project between the FDA, the NIH, and the National Toxicology Program (NTP) that was created to study the effects of BPA exposure at different doses during development and adulthood in rats. CLARITY has two components. The first part was the Core Study which consisted of a two year guideline study measuring potential toxic effects of BPA in rats; this was conducted according to federal validated protocols and guidelines for toxicity testing. The second part of the study involves studies conducted by independent university researchers that test a wide variety of additional endpoints.
Based on interim results of CLARITY-BPA Core Study released in 2018 (the final report is set to be published in fall, 2019), the FDA claimed that there is “no risk of health effects from BPA at typical human exposure levels, even if people are exposed to BPA throughout their lives.”
After reading the FDA’s claim, I wondered about the discrepancy between previous endocrinology scientific literature on BPA and the conclusions from the CLARITY core study. After perusing the details of the CLARITY core data and examining scientists’ responses to CLARITY, I discovered a number of errors within the study methodology and the conclusions drawn by its authors. Below, are the three most disturbing flaws of the CLARITY core study.
1. The authors of the study failed to acknowledge the statistically significant effects of BPA at low doses, disregarding them as ‘sporadic’
The results of CLARITY found that BPA at low doses demonstrated several serious effects, including:
An increased incidence of mamillary adenocarcinoma
Inflammation of the prostate
Kidney disease in females
Increased body weight in adult females
Despite these statistically significant effects, the authors of the study concluded that BPA produced ‘minimal effects that were indistinguishable from the background.’ They concluded this because they did not find the same effects of BPA at high doses or dose responsiveness (an increasing incidence with increasing doses of BPA). It is disconcerting that low dose BPA effects were disregarded given the well-documented knowledge that endocrine disrupting chemicals are known to exhibit significant effects at small doses and in a non-linear fashion. According to an article published in Nature by endocrinology research experts who criticized the CLARITY core study conclusions, there was no “scientific basis for the FDA to dismiss adverse outcomes at low doses.”
2. The presence of confounding variables
The CLARITY study involved comparing a control group of rats, which were not exposed to BPA against a variable group of rats that were exposed to BPA through gavage (the administration of drugs by force typically by placing a tube down the throat to the stomach).
Ironically, In the 90 day pilot study leading up to the actual CLARITY study, the rats in the control group (those NOT exposed to BPA) were incidentally found to have BPA metabolites in their serum and feces when tested. This revealed that the control group was somehow exposed to BPA from an unknown source. The source was never discovered and this confounding problem was never addressed in the actual CLARITY trials. Obviously, if a control group is exposed to the very chemical that is being researched in a trial, this major confounder is likely to result in inaccurate conclusions.
3. The CLARITY study reveals replication flaws within guideline studies
CLARITY is considered a ‘guideline’ study. Guideline studies are large, federally funded studies that use ‘validated protocols, agreed upon international groups, that typically examine overt signs of toxicity.’ Guideline studies are expensive, and supposedly so well-organized that they are deemed reproducible. Therefore, they are usually never repeated. The FDA usually bases its health statements on toxicity on the results of a single guideline study.
The CLARITY study unintentionally tested the reproducibility of another specific guideline study - one measuring the effects of ethinyl estradiol. CLARITY did so by including a positive control group of rats that received ethinyl estradiol, a known EDC, against the effects of BPA. Positive controls ‘ensure that a response to a stimulus can be detected in a biological system.’ Interestingly, in CLARITY the effects of ethinyl estradiol, particularly at low doses, were different than the effects found in the guideline study dedicated to identifying ethinyl estradiol’s effects. In other words, the results of the guideline study testing ethinyl estradiol effects were not reproduced by the CLARITY study. Based on this discovery, the claimed reproducibility of guideline studies may not be as valid as previously assumed.
Why is this Important?
I wrote this article not to necessarily highlight the possibility that BPA may be harmful to humans at current levels of exposure, although this is an important possibility. Still, the possibility remains that BPA at current exposure levels has no effect. After all, the final CLARITY-BPA report does not reach completion until the fall of 2019.
Rather, I wrote this article to underscore the potential fallibility of large authorities that decide upon health-related guidelines. As explained above, the FDA made a statement about BPA safety without thoroughly examining the relevant data. Since the criticisms have surfaced about the major flaws of CLARITY-BPA interim results, the FDA has since removed its most recent claim about BPA on its website. When I searched the FDA’s website, the page describing the FDA’s claim of BPA’s safety based upon CLARITY’s results was no longer to be found: https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm064437.htm.
The FDA is the same institution that determines whether medications and medical devices should be approved. This example highlights the need for individuals, especially scientists, to continue to stay vigilant and to have the wherewithal to scrutinize scientific methods and conclusions, even when they come from authoritative sources, and especially when they relate to individuals’ health.
“In questions of science, the authority of a thousand is not worth the humble reasoning of a single individual.”