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THE 2005 WORLD HEALTH ORGANIZATION RE-EVALUATION OF HUMAN AND MAMMALIAN TOXIC EQUIVALENCY FACTORS FOR DIOXINS AND DIOXIN-LIKE COMPOUNDS
VAN DER BERG, M., L. S. BIRNBAUM, M. DENISON, M. J. DEVITO, W. H. FARLAND, M. FEELEY, H. FIEDLER, H. HAKANSSON, A. HANBERG, L. HAWS, M. ROSE, S. H. SAFE, D. SCHRENK, C. TOHYAMA, A. TRITSCHER, J. TUOMISTO, M. TYSKLIND, N. WALKER, AND R. E. PETERSON. THE 2005 WORLD HEALTH ORGANIZATION RE-EVALUATION OF HUMAN AND MAMMALIAN TOXIC EQUIVALENCY FACTORS FOR DIOXINS AND DIOXIN-LIKE COMPOUNDS. TOXICOLOGICAL SCIENCES. Oxford University Press, Cary, NC, 93(2):223-241, (2006).
To present findings from a 2005 WHO-IPCS expert meeting during which the toxic equivalency factors (TEFs) for dioxin like compounds were re-evaluated
In June 2005 a WHO-IPCS expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin like compounds, including some polychlorinated biphenyls (PCBs), were re-evaluated. For this re-evaluation process the refined TEF database recently published by Haws and coworkers (Toxicol. Sci. 2006, 89:4-30) was used as a starting point. Decisions about a TEF value were made based on a combination of unweighted relative effect potency (REP) distributions from this database, expert judgement and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this re-evaluation it was decided to use half order of magnitude increments on a logarithmic scale of 0.03, 0.1, 0.3 etc. Changes were decided by the expert panel for 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) (TEF=0.3), octachlorodibenzo-p-dioxin (OCDD) and octachlorodibenzofuran (OCDF) (TEFs=0.0003), and one single TEF value (0.00003) for all relevant mono-ortho substituted PCBs. Additivity, an important prerequisite of the TEF concept was again confirmed by results from recent in vivo mixture studies. Some experimental evidence shows that non dioxin-like arylhydrocarbon receptor (AhR) agonists/antagonists are able to impact the overall toxic potency of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds and this needs to be investigated further. Certain individual and groups of compounds were identified for possible future inclusion in the TEF concept, including 3,4,4'-PCB (PCB 37), polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans (PBDFs), mixed polyhalogenated dibenzobenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes and polybrominated biphenyls (PBBs). Concern was expressed about direct application of the TEF/TEQ approach to abiotic matrices such as soil, sediment etc., for direct application in human risk assessment. This is problematic , as the present TEF scheme and TEQ methodology is primarily intended for estimating exposure and risks via oral ingestion (e.g., by dietary intake). A number of future approaches to determine alternative or additional TEFs were also identified. These included the use of a probabilistic methodology to determine TEFs that better describe the associated levels of uncertainty and 'systemic' TEFs for blood and adipose tissue and total Toxic equivalency (TEQ) for body burden.