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Ronald H. White,¹ Ila Cote,² Lauren Zeise,³ Mary Fox,¹ Francesca Dominici,¹ Thomas A. Burke,¹ Paul D. White,⁴ Dale B. Hattis,⁵ and Jonathan M. Samet¹

¹Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; ²U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ³California Environmental Protection Agency, Office of Environmental Health Hazard Assessment, Sacramento, California, USA; ⁴U.S. Environmental Protection Agency, Washington, DC, USA; ⁵Clark University, Worcester, Massachusetts, USA

Abstract
Low-dose extrapolation model selection for evaluating the health effects of environmental pollutants is a key component of the risk assessment process. At a workshop held in Baltimore, Maryland, on 23–24 April 2007, sponsored by U.S. Environmental Protection Agency and Johns Hopkins Risk Sciences and Public Policy Institute, a multidisciplinary group of experts reviewed the state of the science regarding low-dose extrapolation modeling and its application in environmental health risk assessments. Participants identified discussion topics based on a literature review, which included examples for which human responses to ambient exposures have been extensively characterized for cancer and/or noncancer outcomes. Topics included the need for formalized approaches and criteria to assess the evidence for mode of action (MOA) , the use of human versus animal data, the use of MOA information in biologically based models, and the implications of interindividual variability, background disease processes, and background exposures in threshold versus nonthreshold model choice. Participants recommended approaches that differ from current practice for extrapolating high-dose animal data to low-dose human exposures, including categorical approaches for integrating information on MOA, statistical approaches such as model averaging, and inference-based models that explicitly consider uncertainty and interindividual variability. Key words: dose–response function, environmental health, low-dose extrapolation, risk assessment, workshop report. Environ Health Perspect 117:283–287 (2009) . doi:10.1289/ehp.11502 available via http://dx.doi.org/ [Online 19 September 2008]

Address correspondence to R.H. White, Department of Epidemiology, Risk Sciences and Public Policy Institute, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Room W6035, Baltimore, MD 21205 USA. Telephone: (443) 287-5324. Fax: (410) 955-0863. E-mail: rwhite@jhsph.edu

We thank the workshop participants for their contributions to this effort. In addition, we acknowledge R. Chari for assistance with background research and R. Nachman for assistance with manuscript preparation and workshop logistics.

Funding for the workshop was provided under EPA order no. EP06H002881.

The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.

The authors declare they have no competing financial interests.

Received 24 March 2008 ; accepted 19 September 2008.