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Harvard Center for Risk Analysis Expert Panel Finds No Consistent Affirmative Evidence of Low-Dose BPA Effects

September 3, 2004

Summary

An expert scientific panel convened by the Harvard Center for Risk Analysis has concluded that the weight of evidence does not support low-dose effects from Bisphenol A (BPA). Using a comprehensive and systematic framework for their evaluation, the panel found no consistent affirmative evidence of low-dose effects for any endpoint. Reported low-dose effects in laboratory animals, due to their inconsistency, cannot be generalized to humans. In addition, the evidence does not support estrogenicity as a biologically plausible mechanism for low doses of BPA. The panel's results confirm the conclusion reached by every government and scientific body worldwide that has reviewed the evidence for low-dose effects of BPA - the "low-dose hypothesis" is unproven. The comprehensive review provides additional compelling reassurance that there is not a basis for human health concerns from exposure to low doses of BPA.

Weight of Evidence Does Not Support Low-Dose BPA Effects

Since the mid-1990's, claims have been made that extremely low doses of BPA can cause adverse health effects by disruption of normal hormonal functions. According to this so-called "low-dose hypothesis," BPA acts as a synthetic estrogen to cause adverse reproductive and developmental effects at doses far lower than levels shown to cause no effect in conventional toxicity tests. The low-dose claims have generally been based on small-scale studies using non-validated protocols, and the results have not been independently replicated(1). In addition, the claimed low-dose effects have not been found in much larger-scale multigeneration studies that specifically examined low doses(2) .

To resolve any remaining uncertainties from conflicting data and interpretations, the Harvard Center for Risk Analysis(3) convened an expert scientific panel(4) to evaluate the weight of evidence for low-dose reproductive and developmental effects of BPA. To guide their assessment, the panel used a comprehensive and systematic framework that assessed reported low-dose effects against three key criteria: consistency, generalizability across species to humans subjected to environmentally relevant exposures, and biological plausibility.

Low-dose effects reported in the scientific literature examined by the panel failed to meet one or more of the three key criteria. Consequently, in their overall conclusion:

"[T]he panel found no consistent affirmative evidence of low-dose BPA effects for any endpoint. It found that inconsistent responses by various rodent test species also raised doubts as to the generalizability of results to humans. And differences in the pattern of responses to BPA compared to known estrogenic compounds cast doubt on estrogenicity as a low-dose mechanism for BPA."

The panel found that BPA does not exhibit several key characteristics that are typical of estrogenic agents, indicating that BPA is unlikely to be exhibiting estrogenic characteristics in studies that claim low-dose reproductive effects. In any case, the panel noted that the inconsistency of effects across species casts doubt on whether effects reported in mice, even if real, could be extrapolated to humans. A summary of the weight of the evidence evaluation and conclusions is provided in the August 2004 issue of Risk in Perspective, published by the Harvard Center or Risk Analysis. Full details of the study will be published in the October 2004 issue of the peer-reviewed scientific journal Human and Ecological Risk Assessment.(5) Copyright 2004 From Human and Ecological Risk Assessment by George M. Gray. Reproduced by permission of Taylor & Francis, Inc., http://www.taylorandfrancis.com.

Harvard Panel Confirms Conclusions of Government and Scientific Bodies Worldwide

Various government and scientific bodies worldwide have also reviewed the evidence for low-dose effects, in particular from BPA. In every case, based on the weight of the evidence, the "low-dose hypothesis" for BPA has not been accepted. Notable examples include assessments by the European Commission's Scientific Committee on Toxicity, Ecotoxicity and the Environment, Scientific Committee on Food, United States Environmental Protection Agency, and the Japanese Ministry of Health, Labor and Welfare. The results from the Harvard panel fully confirm these earlier conclusions.

Safety of Bisphenol A Reaffirmed

The breadth of evidence examined and the use of a comprehensive and systematic evaluation framework adds significant strength to the Harvard panel's conclusions. These conclusions provide compelling reassurance that there is no basis for human health concerns from exposure to low doses of BPA.

1. For more information on replication of reported low-dose effects, see "Low-Dose Hypothesis Again Not Replicated: Reproducibility is Key Factor in Assessment of Potential Endocrine Disruptors" at http://www.bisphenol-a.org/whatsNew/20021011LowDoseHypothesis.html.

2. For more information on BPA multigeneration studies, see "Definitive Peer-Reviewed Study Reports No Low-Dose Effects" at http://www.bisphenol-a.org/whatsNew/20020702DefinitivePeer.html.

3. The Harvard Center for Risk Analysis (HCRA), part of the Harvard University School of Public Health, was launched in 1989 with the mission to promote public health by using decision sciences to take a broader view. By applying these analytic methods to a wide range of risk issues, and by comparing various risk management strategies, HCRA hopes to empower informed public responses to health, safety and environmental challenges by identifying policies that will achieve the greatest benefits with the most efficient use of limited resources. For more information on HCRA, see http://www.hcra.harvard.edu.

4. The panel was chaired by Donald Mattison, former medical director of the March of Dimes and currently Senior Advisor to the Directors of the Center for Research for Mothers and Children at the National Institute of Child Health and Human Development. Other panel members included Gerald Cunha (Department of Anatomy, University of California, San Francisco), Claude Hughes (Quintile Inc.), Ernest E. McConnell (ToxPath Inc.), Lorenz Rhomberg (Gradient Corp.), I. Glenn Sipes (Department of Pharmacology and Toxicology, University of Arizona), Paul Foster (currently at National Institute of Environmental Health Sciences), Marvin Meistrich (University of Texas at Houston), Heniz Nau (Veterinary Medical University of Hannover), and Richard Sherins (Genetics and IVF Institute), along with George Gray and Joshua Cohen (Harvard Center for Risk Analysis).

5. Gray, G. M., Cohen, J. T., Cunha, G., Hughes, C., McConnell, E. E., Rhomberg, L., Sipes, I. G., and Mattison, D., "Weight of the evidence evaluation of low-dose reproductive and developmental effects of bisphenol A", Human and Ecological Risk Assessment, 10(5):875-921 (2004). Copyright 2004 From Human and Ecological Risk Assessment by George M. Gray. Reproduced by permission of Taylor & Francis, Inc., http://www.taylorandfrancis.com.