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A PRELIMINARY APPROACH TO CHARACTERIZING VARIABILITY AND UNCERTAINTY IN THE MAMMALIAN PCDD/F AND PCB TEFS
Citation:
Haws, L., M. Harris, S. Su, N. Walker, L S. Birnbaum, M J. DeVito, W. H. Farland, K. Connor, A. Santamaria, AND B. Finley. A PRELIMINARY APPROACH TO CHARACTERIZING VARIABILITY AND UNCERTAINTY IN THE MAMMALIAN PCDD/F AND PCB TEFS. Presented at Dioxin 2004, Berlin, Germany, Sept. 3-11, 2004.
Description:
The current toxic equivalency factors (TEFs) for PCDD/Fs and "dioxin-like" PCBs represent consensus-based values that were recommended by an international panel of experts convened by the World Health Organization (WHO) in June of 19971. As a part of the development of the mammalian TEFs, the WHO expert panel considered an extensive body of in vivo and in vitro studies compiled into a database of relative potency (REP) values by scientists at the Karolinska Institute in Stockholm Sweden (hereafter referred to as the Karolinska database). In deriving the TEFs from the underlying REP data, the WHO expert panel employed the following qualitative criteria: 1) in vivo studies were given greater weight than were in vitro studies and/or quantitative structure activity relationship (QSAR) data; 2) chronic studies were given greater weight than were subchronic studies, which were given greater weight than were subacute studies, which were given more weight than were acute studies; and 3) toxic responses were given more weight than were biochemical responses (e.g., enzyme induction)1. In accordance with the procedures for review established by the WHO expert panel, previously established TEFs for PCDD/Fs 2,3 and dioxin-like PCBs4 were retained unless there was sufficient data to support a change1. The final TEFs recommended by the WHO expert panel were determined based on scientific judgment and represent order-of-magnitude estimates of potency for each of the congeners relative to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD).
As has been indicated by a number of investigators, the REP values for many congeners are derived from a highly heterogeneous data set, and, for most TEFs, the range of underlying REP values often spans several orders of magnitude1,5,6,7. However, the degree to which the current "point estimate" TEFs introduce variability and uncertainty into the health risk assessment process cannot be characterized in a quantitative fashion. Such characterizations may be important in settings where numerous PCDD/F and PCB congeners contribute to potential health risk. We believe that the use of REP distributions, as a supplement to or in place of "point estimate" TEFs, might facilitate such characterizations. Specifically, use of a range of REP values, perhaps with a clearly identified "central tendency" (e.g., 50th percentile) and/or "upper bound" (e.g., 90th or 95th percentile), would permit more informed discussions regarding the degree to which the TEFs contribute to variability and uncertainty in health risk estimates. This is important given the widespread use of the TEFs by numerous governmental agencies and others to regulate or otherwise assess potential health risks associated with exposures to this class of compounds. In this analysis, we describe the derivation of REP distributions for certain PCDD/F and PCB congeners using a "refined" REP database that was developed for this purpose