The FDA Flunks

By Sarah Vogel

The Science Board Subcommittee on Food Contact Applications of BPA (Bisphenol A), the expert panel assigned to evaluate the FDAâs Draft Assessment on BPA, released a report Wednesday, October 29, 2008, highlighting a number of severe limitations of the agencyâs assessment.  Although judiciously written, the Subcommittee unequivocally gave the agency failing marks on the scientific quality and rigor of its recent assessment.  The Subcommitteeâs evaluation of what was by all accounts a poorly prepared report deserves considerable praise and attention.

Without going through the report point-by-point, letâs focus on the two fundamental parts of the safety assessment: the exposure assessment and the criteria used to assess studies of BPA.  

Exposure assessment: grade F
The Subcommittee found the FDAâs exposure assessment to be âseverelyâ limited (p. 13) due to its âlack of consideration of the totality of exposures from other sourcesâ, its limited size, geographical and temporal distribution, and unsupported assumptions about infant feeding and methods of heating formula (p. 5).   The extremely limited data in the exposure assessment provided no insight into the variability of exposure over time within a single individual or across populations.  This problem was further exacerbated by the presentation of the data in mean values with no distributions.  The Subcommittee makes it clear that the FDA needs to completely redo their exposure assessment using updated methods and available data on BPA.

Selection of Toxicological Studies: grade F
In its draft assessment, the FDA chose to largely ignore all of the scientific research on BPA save for two multi-generational studies funded by the chemical industry.  I wrote about this here and contributed to an evaluation of these âGood Laboratory Practiceâ studies here.  The major chemical trade association, the American Chemistry Council (ACC), declared these studies to be the gold standard of regulatory toxicology and the FDA accepted this position. 

But the Subcommittee came to a very different conclusion.  First, they found that the FDA failed to provide any explanation of the âRedbook 2000â protocols used by the agency and âdoes not articulate reasonable and appropriate scientific support for the criteria and methods employed in the draft assessment.â (p. 6) The Subcommittee disagreed outright with the FDAâs reliance on the two GLP studies and the agencyâs conclusion that the non-GLP studies should be excluded from the evaluation. 

The one exception to the FDAâs failure to include criteria for evaluating studies, which the Subcommittee accurately noted, was when the agency chose to disqualify a given study (p. 6). Although only briefly mentioned by the Subcommittee, this point begs a follow-up question not addressed in their report: was this just another aspect of a poorly conducted report or is this an example of intentional ineptitude at the agency?  The strategy of tearing down unfavorable data to avoid regulation is a well-known tactic of the tobacco and chemical industries.  (Check out David Michaelsâ Doubt is Their Product). This is an extremely important point to consider because it raises an important question: can the current FDA conduct a transparent, high quality scientific assessment of BPA? 

The Subcommittee found that those non-GLP studies found to be âadequateâ by the Center for the Evaluation of Risks to Human Reproduction should be included in the assessment.  In addition, they concluded that several studies published after the release of the FDAâs assessment needed consideration, including the epidemiological study published by Lang et al. 2008 that found a correlation between urinary BPA levels in adults and coronary heart disease and diabetes[1].   While the Subcommittee noted the limitations of the study, it found that these findings were of concern and âconsideration of this study is warrantedâ (p. 8).   The Subcommittee also mentioned two other studies recently published papers that deserve consideration in the assessment (p. 8)[2]. 

In its final summary, the Subcommittee pin-pointed a key issue to emerge in this debate about BPA:  âthe need for application of state-of-the-art risk assessment methodâ¦which will enable utilizing all appropriate scientific information available on the potential toxicity of BPA.â  This method should include the use of âacademic and government-sponsored studies that are not necessarily GLP-compliantâ (p. 13).  This may be the most important conclusion of the report, but what the Subcommittee doesnât weigh in on is the question that bears repeating: is the FDA capable of such an assessment? 

There is reason to doubt the agencyâs abilities. During the question and answer session at the September 16 meeting, one member of the Subcommittee asked the representative from the FDA about their decision to exclude in the assessment a study found to be âadequateâ by the CERHR panel.  The response from the FDA official was that while she considered the findings âinterestingâ there was nothing they could do with them âquantitatively.â  This answer neither inspires confidence nor reflects the level of scientific rigor and leadership we must demand of our regulatory agencies.

The next steps
The charge to the FDA is to determine if BPA is safe.  Safety, according to the agency âmeans that there is reasonable certainty in the minds of credible scientists that the substance is not harmful under the intended conditions of use.â  The Subcommittee found that the FDAâs safety margin is currently âinadequateâ and its assessment poorly conducted.  Determining BPAâs safety is not a matter of needing more scientific research.  There are already over 700 studies on this chemical.  âCredibleâ minds at the NTP and a consensus of BPA researchers have determined that there are a number of serious risks of exposure to BPA at the levels of human exposure.  The challenge to credible scientists and regulators now is to determine the level and magnitude of the risks presented by current BPA exposure at all developmental stages in life. 

But the challenge presented by this debate over BPA safety extends beyond this one chemical and must be faced by the public, members of Congress and the in-coming Executive Office.   In light of the poor quality of the FDAâs report and serious concerns about the chemical and plastics industryâs involvement in drafting the assessment, can we be assured that the FDA will use the best available science to protect the publicâs health?  Or do we need to consider serious reforms at the agency?

 

Sarah Vogel received her PhD from  Columbia University in the Department of Sociomedical Sciencesâ Center for the History and Ethics of Public Health and Medicine; her dissertation was entitled âPolitics of Plastic: the economic, political and scientific history of bisphenol A.â She holds masterâs degrees in public health and environmental management from Yale University. She authored the case study âBattles Over Bisphenol Aâ at DefendingScience.org.

[1] I. A. Lang et al., "Association of Urinary Bisphenol a Concentration with Medical Disorders and Laboratory Abnormalities in Adults," JAMA 300, no. 11 (2008).
[2] C. Leranth et al., "Bisphenol a Prevents the Synaptogenic Response to Estradiol in Hippocampus and Prefrontal Cortex of Ovariectomized Nonhuman Primates," Proc Natl Acad Sci U S A 105, no. 37 (2008), D. C. Dolinoy et al., "Metastable Epialleles, Imprinting, and the Fetal Origins of Adult Diseases," Pediatr Res 61, no. 5 Pt 2 (2007).