| An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment Frederick S. vom Saal1 and Claude Hughes2,3 1Division of Biological Sciences, University of Missouri, Columbia, Missouri, USA; 2Department of Medical and Scientific Services, Quintiles, Research Triangle Park, North Carolina, USA; 3Department of Biology, East Carolina University, Greenville, North Carolina, USA Abstract
Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent report prepared by the Harvard Center for Risk Analysis and funded by the American Plastics Council concluded that evidence for low-dose effects of BPA is weak on the basis of a review of only 19 studies ; the report was issued after a delay of 2.5 years. A current comprehensive review of the literature reveals that the opposite is true. As of December 2004, there were 115 published in vivo studies concerning low-dose effects of BPA, and 94 of these report significant effects. In 31 publications with vertebrate and invertebrate animals, significant effects occurred below the predicted "safe" or reference dose of 50 µg/kg/day BPA. An estrogenic mode of action of BPA is confirmed by in vitro experiments, which describe disruption of cell function at 10- 12 M or 0.23 ppt. Nonetheless, chemical manufacturers continue to discount these published findings because no industry-funded studies have reported significant effects of low doses of BPA, although > 90% of government-funded studies have reported significant effects. Some industry-funded studies have ignored the results of positive controls, and many studies reporting no significant effects used a strain of rat that is inappropriate for the study of estrogenic responses. We propose that a new risk assessment for BPA is needed based on a) the extensive new literature reporting adverse effects in animals at doses below the current reference dose ; b) the high rate of leaching of BPA from food and beverage containers, leading to widespread human exposure ; c) reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice ; and d) recent epidemiologic evidence that BPA is related to disease in women. Key words: bisphenol A, dose response, endocrine disruptors, low dose, nonmonotonic, risk assessment scientific integrity. Environ Health Perspect 113:926-933 (2005) . doi:10.1289/ehp.7713 available via http://dx.doi.org/ [Online 13 April 2005]
Address correspondence to F.S. vom Saal, Division of Biological Sciences, 105 Lefevre Hall, University of Missouri-Columbia, Columbia, MO 65211 USA. Telephone: (573) 882-4367. Fax: (573) 884-5020. E-mail: vomsaalf@missouri.edu We thank J.P. Myers for comments during the preparation of the manuscript. Funding during the preparation of the manuscript was provided by National Institute of Environmental Health Sciences grant ES11283 to F.S. The authors declare they have no competing financial interests. Received 2 November 2004 ; accepted 12 April 2005.
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