TY - JOUR
T1 - State-of-the-science workshop report
T2 - Issues and approaches in low-dose-response extrapolation for environmental health risk assessment
AU - White, Ronald
AU - Cote, Ila
AU - Zeise, Lauren
AU - Fox, Mary
AU - Dominici, Francesca
AU - Burke, Thomas
AU - White, Paul D.
AU - Hattis, Dale B.
AU - Samet, Jonathan M.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Dose-response function
KW - Environmental health
KW - Low-dose entrapolation
KW - Risk assessment
KW - Workshop report
UR - http://www.scopus.com/inward/record.url?scp=59349119247&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59349119247&partnerID=8YFLogxK
U2 - 10.1289/ehp.11502
DO - 10.1289/ehp.11502
M3 - Article
C2 - 19270800
AN - SCOPUS:59349119247
SN - 0091-6765
VL - 117
SP - 283
EP - 287
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 2
ER -