| A Clash of Old and New Scientific Concepts in Toxicity, with Important Implications for Public Health John Peterson Myers,1 R. Thomas Zoeller,2 and Frederick S. vom Saal3 1Environmental Health Sciences, Charlottesville, Virginia, USA; 2Biology Department, University of Massachusetts, Amherst, Massachusetts, USA; 3Division of Biological Sciences, University of Missouri, Columbia, Missouri, USA Abstract
Background: A core assumption of current toxicologic procedures used to establish health standards for chemical exposures is that testing the safety of chemicals at high doses can be used to predict the effects of low-dose exposures, such as those common in the general population. This assumption is based on the precept that “the dose makes the poison”: higher doses will cause greater effects. Objectives: We challenge the validity of assuming that high-dose testing can be used to predict low-dose effects for contaminants that behave like hormones. We review data from endocrinology and toxicology that falsify this assumption and summarize current mechanistic understanding of how low doses can lead to effects unpredictable from high-dose experiments. Discussion: Falsification of this assumption raises profound issues for regulatory toxicology. Many exposure standards are based on this assumption. Rejecting the assumption will require that these standards be reevaluated and that procedures employed to set health standards be changed. The consequences of these changes may be significant for public health because of the range of health conditions now plausibly linked to exposure to endocrine-disrupting contaminants. Conclusions: We recommend that procedures to establish acceptable exposure levels for endocrine-disrupting compounds incorporate the inability for high-dose tests to predict low-dose results. Setting acceptable levels of exposure must include testing for health consequences at prevalent levels of human exposure, not extrapolations from the effects observed in high-dose experiments. Scientists trained in endocrinology must be engaged systematically in standard setting for endocrine-disrupting compounds. Key words: biphasic, bisphenol A, dose–response curve, inverted U, low dose, nonmonotonic, regulatory toxicology. Environ Health Perspect 117:1652–1655 (2009) . doi:10.1289/ehp.0900887 available via http://dx.doi.org/ [Online 30 July 2009]
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 We thank L. Birnbaum, P. Ehrlich, D. Epel, P. Hunt, D. Kennedy, P. Lee, and S. Vogel for comments on the manuscript. J.P.M. is CEO/chief scientist for Environmental Health Sciences (EHS) , a not-for-profit organization that receives support from several private foundations (listed at http://www.environmentalhealthnews.org/about.html) to support EHS’s mission to advance public understanding of environmental health sciences. In addition to serving on the faculty of the University of Missouri, F.v.S. is CEO of XenoAnalytical LLC, a small private laboratory that performs assays of xenobiotic compounds. R.T.Z. declares he has no competing financial interests. Received 10 April 2009 ; accepted 29 July 2009.
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