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John Peterson Myers,¹ Frederick S. vom Saal,² Benson T. Akingbemi,³ Koji Arizono,⁴ Scott Belcher,⁵ Theo Colborn,⁶ Ibrahim Chahoud,⁷ D. Andrew Crain,⁸ Francesca Farabollini,⁹ Louis J. Guillette Jr.,¹⁰ Terry Hassold,¹¹ Shuk-mei Ho,¹² Patricia A. Hunt,¹¹ Taisen Iguchi,¹³ Susan Jobling,¹⁴ Jun Kanno,¹⁵ Hans Laufer,¹⁶ Michele Marcus,¹⁷ John A. McLachlan,¹⁸ Angel Nadal,¹⁹ Jörg Oehlmann,²⁰ Nicolás Olea,²¹ Paola Palanza,²² Stefano Parmigiani,²² Beverly S. Rubin,²³ Gilbert Schoenfelder,²⁴ Carlos Sonnenschein,²³ Ana M. Soto,²³ Chris E. Talsness,²⁵ Julia A. Taylor,² Laura N. Vandenberg,²³ John G. Vandenbergh,²⁶ Sarah Vogel,²⁷ Cheryl S. Watson,²⁸ Wade V. Welshons,²⁹ and R. Thomas Zoeller³⁰

¹Environmental Health Sciences, Charlottesville, Virginia, USA; ²Division of Biological Sciences, University of Missouri, Columbia, Missouri, USA; ³Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA; ⁴Faculty of Environmental and Symbiotic Science, Prefectural University of Kumamoto, Tsukide, Kumamoto, Japan; ⁵Department of Pharmacology and Cell Biophysics, Center for Environmental Genetics, University of Cincinnati, Cincinnati, Ohio, USA; ⁶The Endocrine Disruption Exchange, Paonia, Colorado, USA; ⁷Institut für Klinische Pharmakologie und Toxikologie Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; ⁸Department of Biology, Maryville College, Maryville, Tennessee, USA; ⁹Dipartimento di Fisiologia, Universitŕ di Siena, Siena, Italy; ¹⁰Department of Zoology, University of Florida, Gainesville, Florida, USA; ¹¹School of Molecular Biosciences, Washington State University, Pullman, Washington, USA; ¹²Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio, USA; ¹³National Institutes of Natural Science, Okazaki Institute for Integrative Bioscience, Bioenvironmental Science, Okazaki, Japan; ¹⁴Department of Biological Sciences, Brunel University, Uxbridge, United Kingdom; ¹⁵Division of Cellular and Molecular Toxicology, National Institute of Health Sciences, Tokyo, Japan; ¹⁶Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA; ¹⁷Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; ¹⁸Center for Bioenvironmental Research, Tulane and Xavier Universities, New Orleans, Louisiana, USA; ¹⁹Instituto de Bioingeniería and CIBERDEM, Universidad Miguel Hernández de Elche, Alicante, Spain; ²⁰Goethe University Frankfurt am Main, Department Aquatic Ecotoxicology, Frankfurt, Germany; ²¹Hospital Clínico, CIBERESP, University of Granada, Granada, Spain; ²²Dipartimento di Biologia Evolutiva e Funzionale, Universita' di Parma, Parma, Italy; ²³Tufts Medical School, Boston, Massachusetts, USA; ²⁴Institute of Pharmacology and Toxicology, University of Wuerzburg, Wuerzburg Germany; ²⁵Charité University Medical School Berlin, Berlin, Germany; ²⁶Department of Biology, North Carolina State University, Raleigh, North Carolina, USA; ²⁷Chemical Heritage Foundation, Philadelphia, Pennsylvania, USA; ²⁸Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA; ²⁹Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA; ³⁰Biology Department, University of Massachusetts, Amherst, Massachusetts, USA

Abstract
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]

Address correspondence to J.P. Myers, Environmental Health Sciences, 421 Park St., Charlottesville, VA 22902 USA. Telephone: (434) 220-0348. Fax: (434) 220-0347. E-mail: jpmyers@ehsic.org

The authors declare they have no competing financial interests.

Received 9 September 2008 ; accepted 22 October 2008.