by Sarah Vogel

Sometimes there is a study that changes everything.  On Tuesday, January 12, 2010, PLoS ONE, an open access scientific journal, published a large epidemiological study that could become the straw that breaks the political logjam over the safety of bisphenol A (BPA).  Researchers at the University of Exeter in the U.K. reported a significant association between levels of BPA in human urine and cardiovascular disease diagnosis.  The findings were significant and robust.  Moreover, the study replicated findings published in 2009 by the same research team.  [see Melzer D, Lang IA, Galloway TS (2009) Association of bisphenol A with diabetes and other abnormalities reply. Journal of the American Medical Association 301: 721–722.]  These studies are the first of their kind and they are alarming.  

The Centers for Disease Control and Prevention’s (CDC) U.S. National Health and Nutrition Survey (NHANES) made this recent research possible. This national survey, begun in the early 1960s, collects health and nutrition information from a representative subpopulation of the US.  Its goal is to provide health statistics for the country— snap shots of American’s health used to guide public health policy and interventions.  Over time focus of NHANES has changed to reflect important new areas of public health concern including, most recently, BPA.

Thanks to the high quality of both the NHANES data and the UK researchers’ work, these studies ought to convince FDA that it’s time to make a decision about the safety of BPA.

NHANES is cross-sectional by design, which means individuals are surveyed at one point in time.  Each survey year a new random sample of Americans is selected.  One-third of the NHANES sample populations in 2003-04 and 2005-06 were randomly selected to provide a urine sample.  These urine samples were then analyzed for BPA.  The UK researchers then compared BPA urine levels with cardiovascular disease diagnosis, collected through interviews and defined as angina, heart attack or coronary heart disease.  The large number of subjects in the study population allowed the U.K. researchers to adjust for many possible confounding factors of cardiovascular disease. 

Studies of this design can be easily dismissed.  The American Chemistry Council (ACC) has already done so, and steadfastly upholds the safety of BPA.  Common criticisms of cross- sectional studies are that they reflect only one point in time—a far cry from determining cause and effect.  Moreover, the use of NHANES data means relying on self-reports of disease, rather than blinded, quantitative diagnosis.  But these studies have notable strengths that cannot be overlooked. First, they allow researchers to examine the health effects of low-dose chemical exposure quickly and, because of the major investment made by the CDC, cheaply.  The CDC makes its high-quality NHANES biomonitoring data publicly available to researchers for free, which provides enormous public value.

Second, this study overcame technical and moral challenges to conducting human research on chemical exposures.  The gold standard in science is the double-blind, randomized, placebo controlled study.   To conduct such a study, one would need to find a representative control population without BPA exposure.  Yet, the CDC’s data finds that over 90% of Americans are exposed to the compound.  There is also the obvious moral problem.  Researchers cannot knowingly and ethically expose humans to BPA.   The next best step is to conduct longitudinal studies that follow individuals over time to provide temporal context for the relationship between exposure and disease.  These are necessary, but such studies are very time consuming and expensive.   

This brings us back to the debate about BPA safety.  Thirteen years of extensive laboratory research on the effects of low-level BPA exposure—levels below the current safety standard—have raised serious concerns about the effects of BPA on reproductive, behavioral and metabolic development and function.  However, the regulatory status quo for BPA is that it is safe.  The Food and Drug Administration began a process to re-evaluate the safety of BPA in 2007-08, but the agency has yet to reach a decision. A delay was welcomed, however, due to the poor quality of the initial draft assessment.  That was in 2008.  Things have changed.   Under new leadership, the FDA is taking seriously the BPA assessment, and is expected to be looking at the complete body of scientific literature on the chemical—including, one would suspect, this recent epidemiological study.  Make no mistake, the task before the agency is political minefield.  They must answer a seemingly simple question regarding a complex body of research:  is BPA safe? 

The current status quo of BPA safety is based on handful of regulatory toxicity tests that for too long have been conflated with the best available science for decision-making.  While these regulatory studies are large in size with many doses, they, like all studies, are limited by the questions they ask, the doses used, the effects measured, the animals selected, etc.  They represent just one piece of a large and complex puzzle the agency must put together in evaluating BPA’s safety.  The hundreds of other published studies must also be considered.  Many of these are small and examine very specific modes of action or endpoints. These too are pieces of the puzzle.  The picture that emerges as the agency puts the pieces of this jigsaw puzzle together will not be complete—science is driven by uncertainty.   Yet, the agency must also be acutely aware that the body of research on BPA is unusually extensive. 

Here is the question the agency must answer for the public, chemical producers and retailers:  “Is  there reasonable certainty in the minds of credible scientists that the substance is not harmful under the intended conditions of use?”  This is a first step.  If the answer is no, this will send a strong signal to producers, retailers, and chemical manufacturers that safer alternatives need to be developed.  This development of alternatives is the next step and one that is already being taken by some manufacturers.  However, the alternatives must also be determined to be safe.  As with the assessment of BPA’s safety, this must be determined based on what is known.  This means that a safe alternative is not simply one that is “not BPA.”   Too often alternatives replace known hazards with little to no data.  It’s an illogical process that generates tremendous distortions in the marketplace.  Read more about this problem and steps towards reforming chemicals management here

The agency cannot take both of these steps at the same time.  First, they must make an assessment of BPA’s safety.  There is ample data to do so today.  More research planned by NIEHS will continue to fill in the endless data gaps. It will also help refine the critical next steps, such as using the BPA evaluative process as a model for reforming the use of science in regulatory decision making, and informing data needs for safety assessments in the future.  But, these next steps can only be reached once the agency completes its first task.  Is BPA safe?

Sarah Vogel received her PhD from  Columbia University in the Department of Sociomedical Sciences’ Center for the History and Ethics of Public Health and Medicine; her dissertation was entitled “Politics of Plastic: the economic, political and scientific history of bisphenol A.” She holds master’s degrees in public health and environmental management from Yale University. She authored the case study “Battles Over Bisphenol A” at