by Sarah Vogel
Last Friday, January 15, 2010, senior officials from the Department of Health and Human Services, the FDA, and the National Institute of Environmental Health Sciences (NIEHS) held a press conference to detail the FDA’s next steps on the controversial chemical, bisphenol A (BPA). In a shift from its past policy, the FDA announced its agreement with the National Toxicology Program’s Monograph on BPA (conducted in 2007 and released in 2008), which found “some concern” for developmental effects on the brain, behavior and prostate in fetuses, infants and children.
Make no mistake, this is a significant change from the draft assessment issued by the FDA in 2008 that upheld the safety of BPA. In Friday’s announcement, they presented the public with reason to be cautious and the chemical producers with a signal that they would like to see the development of safer alternatives. It is also important to note that this was not a final decision. Rather, it was a first step and one that holds the promise of leading towards a more integrated use of science in regulatory decision-making.
In their 2008 draft assessment, the FDA based its decision of safety on two large studies funded by the chemical trade association. The agency’s logic at the time for relying on only two studies—when hundreds appeared in the published literature—was that they were conducted by laboratories certified as using Good Laboratory Practices (GLP). GLP guidelines provide necessary governmental oversight of private labs by establishing basic standards for conducting research. However, in the 2008 FDA draft assessment, the agency inappropriately conflated GLP studies with the best available science—the most relevant and reliable evidence for setting regulatory standards. This in turn meant that the agency at the time considered research funded through the NIH as insufficient for regulatory assessment.
The FDA’s recent announcement, therefore, signals an end to this very limited use of science in assessing chemical safety. The announcement also included another important piece of news: FDA will be undertaking a greater collaborative effort with NIEHS on BPA’s safety. From the moment she came to the FDA, Commissioner Hamburg announced reform of regulatory science as a priority. These latest developments suggest that the agency is starting to undertake this significant challenge.
What does it mean to reform regulatory science? In part, it involves updating methods and study designs and expanding the endpoints assessed in regulatory toxicity tests. For example, over the past four decades NIEHS has supported leading-edge research on the transplacental and low-dose effects of chemicals, including estrogenic compounds and endocrine disrupting chemicals. Yet, the study design used by the NTP to evaluate carcinogenesis does not include in utero exposure and reproductive toxicity tests continue to use very high exposures to evaluate effects at low levels. Ten years ago when the NTP evaluated low dose effects of endocrine disrupting chemicals, they concluded that the testing “paradigm” used in reproductive and developmental studies needed to be re-evaluated to consider exposure to endocrine disruptors.
As demonstrated by the case of BPA, scientific research over the past decade has pointed to new mechanisms of action, new endpoints and new areas of public health concern unexamined by regulatory toxicity tests. Re-evaluation of the testing paradigm is now long overdue and BPA provides the perfect opportunity for reform.
The NIEHS is spending $30 million over the next several years on key studies of BPA. Considering the time, effort and money spent on the evaluation of BPA, the outcome should contribute not only to a coordinated response across the regulatory agencies; it should also provide a case study for identifying priority areas for reforming regulatory science and the testing paradigm used to evaluate endocrine disruptors. These efforts will require formalized collaboration between regulatory agencies (FDA, EPA, CPSC and OSHA) and the NIEHS with input and support from the scientific community.
Where might this begin? One small step is with the NTP Monograph. The Monograph on BPA provided an in-depth, rigorous review of the existing scientific literature, but it will need updating as research is completed. It’s important to note, however, that there are specific limits to this report. Since the Monograph is part of the Center for Risks to Human Reproduction, only reproductive and developmental effects are evaluated. This leaves out some of the latest research on BPA’s effects on non-reproductive endpoints, such as insulin and metabolic regulation. As a result, there will need to be an evaluation of the existing literature on other endpoints, particularly those that might contribute to diseases of public health importance, including diabetes, obesity and cardiovascular disease.*
Strengthening and expanding the evaluative tools used by the NIEHS and prioritizing updates and reform of the testing paradigm will improve the scientific foundation upon which all agencies make regulatory decisions. At the end of December 2009, the EPA announced its Chemical Action Plans for priority chemicals, including BPA. These new plans are currently undergoing review at the Office of Management and Budget (OMB). The EPA’s decision on BPA could have a much broader impact on the use and exposure to this chemical. The agency will need a strong, rigorous, extensive and up-to-date evaluation of the existing literature from the NIEHS.
For an in-depth analysis on the FDA’s recent announcement and links to news reports on the issue, see this recent essay.
*This latter issue points to the need to expand the chemical profile reports issued by the NTP. This would follow a historical trend. For example, when the NTP was established in 1978 it took over responsibility of the Carcinogenesis Bioassay Program. Under the direction of David Rall, the program expanded into reproductive and developmental toxicity. Most recently, the Center for Risks to Human Reproduction was established in 1994 and issues monograph reports like the one on BPA.
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 DefendingScience.org.