By Jocelyn Duffy
In a recent Grand Rounds webinar on bisphenol-A (BPA), the FDA dismissed research findings that showed low levels of BPA exposure caused serious health effects in an animal model. In a webinarorganized by Carnegie Mellon University’s Institute for Green Science and Environmental Health Sciences, a group of leading BPA researchers strongly disagreed with this dismissal.
“Research from many investigators in many labs have shown that BPA exposure has serious health risks,” said Terry Collins, director of Carnegie Mellon’s Institute for Green Science and Teresa Heinz Professor of Green Chemistry. “And as we detailed in our recent IGS review of BPA distribution, there appears to be no life-significant pocket of the ecosphere that is not already contaminated by BPA.
“Endocrine disrupting chemicals, among which BPA is a poster child, disrupt normal development and could be stealing away the health and reproductive ability of our species, even rapidly,” Collins added. “A recent report by Hagai Levine, Shanna Swan and colleagues describing an analysis of the literature on sperm count decline in Western man proves that this theft is well underway, where developmental disruptors are top suspects. The meta-analysis study and its ominous implications for humanity have been superbly explained by Daniel Noah Halpern in GQ magazine. It was our duty to provide a forum where this amazing research could be discussed openly.”
To address the claims made in the FDA Grand Rounds, IGS and EHS assembled a panel of some of the nation’s leading authorities and researchers studying how endocrine disrupting chemicals like BPA impact health. The panelists included Jerrold J. Heindel, former scientific program administrator in the Division of Extramural Research and Training at the U.S. National Institute of Environmental Health Sciences and current director or the Commonweal Program on Endocrine Disruption Strategies; Laura Vandenberg, associate professor of Environmental Health Sciences at the University of Massachusetts at Amherst; Gail S. Prins, the Michael Reese Professor of Urology and Physiology at the University of Illinois at Chicago; and Patricia Hunt, the Meyer Distinguished Professor in the School of Molecular Biosciences at Washington State University.
When regulatory agencies like the FDA make recommendations, they are usually based on a type of study called a guideline study that follows federally approved guideline protocols. These studies are often seen as unnuanced, and their results are can be at odds with what is found in independent labs that use different protocols. Guideline studies assume that the effects of exposure will worsen as the amount of exposure increases. Independent researchers often find that this isn’t the case, sometimes the most significant effects can happen at low doses and not be seen at higher doses.
To address this discrepancy, the FDA, the National Institute of Environmental Health Sciences and the National Toxicology Program launched the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) program six years ago. CLARITY-BPA was intended to combine findings from a standard FDA guideline study with results from 14 independent studies funded by the National Institute of Environmental Health Sciences.
“Clarity was founded to help resolve a major conundrum facing efforts to determine whether low doses of BPA? – those experienced by many people in the U.S. and around the world – are safe,” said panel moderator Pete Myers, an adjunct professor of chemistry at Carnegie Mellon, a member of the Institute for Green Science and chief scientist of Environmental Health Sciences. “Guideline studies conducted by industry for regulatory authorities report that those levels are safe. Many studies from university labs around the world and some government agencies in Europe find differently.”
While the guideline and independent studies addressed different levels of exposure to BPA, the lowest-level exposure – 2.5 micrograms per kilogram per day is the dose with the most contention. This amount is similar to what an average American adult could expect to encounter in their daily life – from touching BPA coatings on receipts, plastic bottles, food and beverage containers and thousands of other consumer products.
In a Sept. 13 Grand Rounds webinar presented by Dr. K. Barry Delclos, the FDA presented an analysis of the study decidedly favoring the guideline study approach. They dismissed the low dose effects because the effects were not seen in high doses.
The consensus among the Carnegie Mellon/EHS expert panel was much different. The experts felt that the available data did not reflect any claim for safety of BPA at low doses. Rather, it showed that exposure to BPA at low levels is not safe. The FDA core studies found serious health effects including increases in breast cancer, prostate inflammation and kidney nephropathy at the lowest doses studied.
“Ignoring the effects of low doses is wrong,” Vandenberg said.”Especially when we are talking about cancer, observing increased disease in animals is concerning at any dose.”
Results from all of the 14 independent CLARITY-BPA studies have not yet been published, those that have been published, nor has a comprehensive CLARITY-BPA report. But in the independent studies that have been published, researchers found the low-level exposure to BPA resulted in elevated prostate cancer risk, reduced ovarian follicle numbers and health, changes in brain regions that regulate anxiety, altered expression of genes in sex-specific regions of the brain, and increased severity of heart muscle damage in young females, among many other effects. Of the 75 health-related endpoints where significant changes were noted in the FDA core studies and published independent CLARITY-BPA studies, more than half occurred only at low dose exposures to BPA.
The panel also noted that the CLARITY-BPA studies had many flaws, including using historical controls that didn’t account for environmental exposure to BPA for the guideline study and the possible contamination of the rat model used for all studies.
Despite these challenges, the researchers still believe that the findings remain a cause for concern. They hope regulatory agencies will continue to work with independent researchers to collect data to get a fuller picture of how chemicals like BPA can impact health and certainly that the FDA will recommend that the public be better protected from BPA.
Carnegie Mellon University