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Development of Weighted Distributions of REPs for Dioxin-Like Compounds: Implications for Risk Assessment
Citation:
Haws, L. C., M. J. DEVITO, N. J. Walker, L. S. BIRNBAUM, K. M. Unice, M. A. Harris, A. Tachovsky, W. H. FARLAND, B. F. Finley, AND D. STASKAL. Development of Weighted Distributions of REPs for Dioxin-Like Compounds: Implications for Risk Assessment. Presented at Society of Toxicology Annual Meeting, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
In their recent reevaluation of the TEF methodology, the WHO expert panel indicated that consideration should be given to developing weighted distributions of REP values to establish TEFs for each dioxin-like compound (DLC). As such, we developed a consensus-based weighting framework where greater emphasis is placed on those REP values from studies of higher quality and those that are believed to be more relevant for assessment of human health risks.
Description:
In their recent reevaluation of the TEF methodology, the WHO expert panel indicated that consideration should be given to developing weighted distributions of REP values to establish TEFs for each dioxin-like compound (DLC). As such, we developed a consensus-based weighting framework where greater emphasis is placed on those REP values from studies of higher quality and those that are believed to be more relevant for assessment of human health risks. In this case study, the impact of using weighted REP distributions was evaluated by calculating fish ingestion dose estimates using three approaches: WHO TEFs, point estimate TEFs based on a series of consistent percentiles from the weighted and unweighted distributions, and using the full weighted and unweighted distributions in a Monte Carlo analysis. Preliminary results indicate that while unweighted distributions tend to yield higher dose estimates than do weighted distributions, the differences are within an order of magnitude regardless of whether a consistent percentile is chosen or the full distribution is used in a Monte Carlo analysis. Dose estimates calculated using the WHO TEFs were found to be consistent with dose estimates calculated using the 50th percentile of the weighted and unweighted distributions; however, at higher percentiles, dose estimates determined based on the unweighted and weighted distributions were 1-2 orders of magnitude higher than estimates using WHO TEFs. These results indicate that use of distributions, particularly when the upper percentiles were utilized as relative potency metrics, had a greater impact on the dose estimates than did the weighting process alone. Overall, these findings suggest that use of weighted distributions of REPs could have significant implications for assessing human health risks.