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ToxSci Advance Access originally published online on August 24, 2005
Toxicological Sciences 2006 89(1):4-30; doi:10.1093/toxsci/kfi294
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

REVIEW

Development of a Refined Database of Mammalian Relative Potency Estimates for Dioxin-like Compounds

Laurie C. Haws*,1, Steave H. Su{dagger}, Mark Harris{ddagger}, Michael J. DeVito§, Nigel J. Walker, William H. Farland||, Brent Finley||| and Linda S. Birnbaum§

* ChemRisk, 8024 Mesa Dr., #126, Austin, Texas 78731; {dagger} Exponent, Inc., 420 Lexington Ave., Suite 1740, New York, New York 10170; {ddagger} ChemRisk, 10375 Richwood Ave., Suite 350, Houston, TX 77042; § U.S. Environmental Protection Agency, ORD NHEERL ETD, MD-B143-01, Research Triangle Park, North Carolina 27709; National Institute of Environmental Health Sciences, Environmental Toxicology Program, P.O. Box 12233, Mail Drop EC-34, Research Triangle Park, North Carolina 27709; || U.S. Environmental Protection Agency, Office of Research and Development, 1200 Pennsylvania Avenue, MC 8101 R, Washington, District of Columbia 20460; and ||| ChemRisk, 25 Jessie St., Suite 1900, San Francisco, CA 94105

Received June 13, 2005; accepted August 17, 2005

The toxic equivalency factor (TEF) approach has been widely accepted as the most feasible method available at present for evaluating potential health risks associated with exposure to mixtures of dioxin-like compounds (DLCs). The current mammalian TEFs for the DLCs were established by the World Health Organization (WHO) following the meeting of an international expert panel in June of 1997. The TEFs recommended by WHO were determined based on a consensus of scientific judgment and were presented as point estimates. However, the relative potency estimates (REPs) underlying the TEFs were derived from a heterogeneous data set and often span several orders of magnitude. In this article, we present a refined database of mammalian REPs that we believe will facilitate better characterization of the variability and uncertainty inherent in the data. The initial step involved reviewing the REP database used by the WHO panel during its review in 1997. A set of criteria was developed to identify REPs that were determined to be the most representative measure of a biological response and of adequate quality for use in quantitative analyses. REPs were determined to be inappropriate for use in quantitative analyses if any of the established exclusion criteria were met. Comparison of data records to the established exclusion criteria resulted in the identification of a substantial number of REPs believed to be inappropriate for use in quantitative analyses. Next, studies published after 1997 were added to the database. The availability of such a refined database will improve risk assessment for this class of compounds by including additional information from new studies and facilitating the use of quantitative approaches in the further development of TEFs.

Key Words: dioxin; polychlorinated dibenzo-p-dioxins; polychlorinated dibenzofurans; polychlorinated biphenyls; toxic equivalency factor (TEF); relative potency (REP).


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