title: State-of-the-science workshop report: issues and approaches in low-dose-response extrapolation for environmental health risk assessment.
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.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. rwhite@jhsph.edu
authors.forename: Ronald H
authors.initials: RH
authors.lastname: White
authors.forename: Ila
authors.initials: I
authors.lastname: Cote
authors.forename: Lauren
authors.initials: L
authors.lastname: Zeise
authors.forename: Mary
authors.initials: M
authors.lastname: Fox
authors.forename: Francesca
authors.initials: F
authors.lastname: Dominici
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Burke
authors.forename: Paul D
authors.initials: PD
authors.lastname: White
authors.forename: Dale B
authors.initials: DB
authors.lastname: Hattis
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Samet
mesh_terms: D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects*; D008396:Maryland; D009369:Neoplasms; D018570:Risk Assessment / Q000379:methods*; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D004785:Environmental Pollutants