You are here:
DEVELOPMENT OF WEIGHTED DISTRIBUTIONS OF REPS FOR DIOXIN-LIKE COMPOUNDS
Citation:
HAWS, L. C., N. J. WALKER, M. J. DEVITO, L. S. BIRNBAUM, K. M. UNICE, P. K. SCOTT, M. A. HARRIS, W. H. FARLAND, B. L. FINLEY, AND D. STASKAL. DEVELOPMENT OF WEIGHTED DISTRIBUTIONS OF REPS FOR DIOXIN-LIKE COMPOUNDS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.
Description:
Potential health risks associated with exposure to mixtures of dioxin-like compounds are currently assessed using a toxic equivalency factor (TEF) approach. Recently, both the WH0 and NAS reviewed the TEF methodology and acknowledged the importance of better characterizing variability and uncertainty inherent in the TEFs. This is important because the single point estimate TEFs recommended by WHO are based on underlying REP values that represent a heterogeneous data set and range across several orders of magnitude. Both the WHO and NAS indicated that use of distributions of REPs would provide a means of characterizing the variability and uncertainty inherent in the TEFs. Development of a framework to quantitatively weight studies based on quality and relevance to human health risk assessment is a central component of developing distributions of REPs for each congener. As such, the aim of this investigation was to develop a transparent and reproducible weighting scheme, to apply it to the REP (Haws et al, 2006) database, and to evaluate the impact on the distributions. The consensus-based weighting scheme incorporates several different measures of study quality and relevance including REP derivation method and quality, pharmacokinetics, study type, and endpoint. Multiple iterations and numerical scales were assessed to determine the impact on the REP distributions. This weighting scheme provides an approach for placing greater emphasis on those REP values that are believed to be more well suited for health risk assessment purposes Application of the weighting scheme to PCB126 and 2,3,4,7,8-PeCDF, the two most data-rich congeners, had very little impact on the overall distribution. Other congeners were assessed as well. Although the weighting scheme did not have a significant impact on the overall distributions, the use of such a scheme yields a more transparent, reproducible, and consistent method for deriving TEFs from the underlying REP data. (This abstract does not reflect Agency policy.)