Why Public Health Agencies Cannot Depend on Good Laboratory Practices as a Criterion for Selecting Data: The Case of Bisphenol A
Myers, John Peterson, vom Saal, Frederick S., Akingbemi, Benson T., Arizono, Koji, Belcher, Scott, Colborn, Theo, Chahoud, Ibrahim, Crain, D. Andrew, Farabollini, Francesca, Guillette, Louis J., Jr., Hassold, Terry, Ho, Shuk-mei, Hunt, Patricia A., Iguchi, Taisen, Jobling, Susan, Kanno, Jun, Laufer, Hans, Marcus, Michele, McLachlan, John A., Nadal, Angel, Oehlmann, Jorg, Olea, Nicolas, Palanza, Paola, Parmigiani, Stefano, Rubin, Beverly S., Schoenfelder, Gilbert, Sonnenschein, Carlos, Soto, Ana M., Talsness, Chris E., Taylor, Julia A., Vandenberg, Laura N., Vandenbergh, John G., Vogel, Sarah, Watson, Cheryl S., Welshons, Wade V., Zoeller, R. Thomas, Environmental Health Perspectives
BACKGROUND: In their safety evaluations of bisphenol A (BPA), the U.S. Food and Drug Administration (FDA) and a counterpart in Europe, the European Food Safety Authority (EFSA), have given special prominence to two industry-funded studies that adhered to standards defined by Good Laboratory Practices (GLP). These same agencies have given much less weight in risk assessments to a large number of independently replicated non-GLP studies conducted with government funding by the leading experts in various fields of science from around the world.
OBJECTIVES: We reviewed differences between industry-funded GLP studies of BPA conducted by commercial laboratories for regulatory purposes and non-GLP studies conducted in academic and government laboratories to identify hazards and molecular mechanisms mediating adverse effects. We examined the methods and results in the GLP studies that were pivotal in the draft decision of the U.S. FDA declaring BPA safe in relation to findings from studies that were competitive for U.S. National Institutes of Health (NIH) funding, peer-reviewed for publication in leading journals, subject to independent replication, but rejected by the U.S. FDA for regulatory purposes.
DISCUSSION: Although the U.S. FDA and EFSA have deemed two industry-funded GLP studies of BPA to be superior to hundreds of studies funded by the U.S. NIH and NIH counterparts in other countries, the GLP studies on which the agencies based their decisions have serious conceptual and methodologic flaws. In addition, the U.S. FDA and EFSA have mistakenly assumed that GLP yields valid and reliable scientific findings (i.e., "good science"). Their rationale for favoring GLP studies over hundreds of publically funded studies ignores the central factor in determining the reliability and validity of scientific findings, namely, independent replication, and use of the most appropriate and sensitive state-of-the-art assays, neither of which is an expectation of industry-funded GLP research.
CONCLUSIONS: Public health decisions should be based on studies using appropriate protocols with appropriate controls and the most sensitive assays, not GLP. Relevant NIH-funded research using state-of-the-art techniques should play a prominent role in safety evaluations of chemicals.
KEY WORDS: bisphenol A, endocrine disruptors, FDA, Food and Drug Administration, GLP, good laboratory practices, low-dose, nonmonotonic, positive control. Environ Health Perspect 117:309-315 (2009). doi:10.1289/ehp.0800173 available via http://dx.doi.org/ [Online 22 October 2008]
Regulatory agencies in the United States and the European Union (EU) have justified the decision to declare the estrogenic chemical bisphenol A (BPA) safe at current levels of human exposure based on a few studies conducted using Good Laboratory Practices (GLP). In contrast, these agencies have rejected for consideration in their risk assessment of BPA hundreds of laboratory animal and mechanistic cell culture studies conducted by academic and government scientists reporting harm at very low doses of BPA. These studies were rejected primarily because they were not conducted using GLP. We suggest that decisions based on this logic are misguided and will result in continued risk to public health from exposure to BPA, as well as other manmade chemicals.
GLP is a federal rule for conducting research on the health effects or safety testing of drugs or chemicals submitted by private research companies for regulatory purposes. The GLP outlines basic guidelines for conducting scientific research, including the care and feeding of laboratory animals, standards for facility maintenance, calibration and care of equipment, personnel requirements, inspections, study protocols, and collection and storage of raw data (Goldman 1988). These regulations were developed in response to widespread misconduct by private research companies; this misconduct was possible because their data usually do not go through the rigorous, multistage scientific review that is normal for academic data funded by federal agencies and published in the peer-reviewed literature. …