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ToxSci Advance Access originally published online on July 7, 2006
Toxicological Sciences 2006 93(2):223-241; doi:10.1093/toxsci/kfl055
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

REVIEW

The 2005 World Health Organization Reevaluation of Human and Mammalian Toxic Equivalency Factors for Dioxins and Dioxin-Like Compounds

Martin Van den Berga,1, Linda S. Birnbaumb, Michael Denisonc, Mike De Vitob, William Farlandd, Mark Feeleye, Heidelore Fiedlerf, Helen Hakanssong, Annika Hanbergg, Laurie Hawsh, Martin Rosei, Stephen Safej, Dieter Schrenkk, Chiharu Tohyamal, Angelika Tritscherm, Jouko Tuomiston, Mats Tysklindo, Nigel Walkerp and Richard E. Petersonq

a World Health Organization Collaborating Centre for Research on Environmental Health Risk Assessment and Institute for Risk Assessment Sciences, Faculties of Veterinary Medicine, Science and University Medical Center, Universiteit Utrecht, PO Box 80177, 3508 TD Utrecht, The Netherlands; b National Health & Environmental Effects Research Laboratory, United States Environmental Protection Agency Research Triangle Park, North Carolina 27709; c Department of Environmental Toxicology, University of California at Davis, Davis, California 95616-8501; d Office of Research and Development, U.S. Environmental Protection Agency (EPA), NW, Washington, District of Columbia 20460; e Chemical Health Hazard Assessment Division, Bureau of Chemical Safety, Health Canada, Tunney's Pasture, Ottawa, Ontario K1A OL2, Canada; f United Nations Environment Program Chemicals, International Environment House, CH-1219 Châtelaine (GE), Switzerland; g Institute of Environmental Medicine, Karolinska Institutet, Unit of Environmental Health Risk Assessment, S-171 77 Stockholm, Sweden; h ChemRisk, Austin, Texas; i Central Science Laboratory, Sand Hutton, YO41 1LZ York, United Kingdom; j Veterinary Physiology and Pharmacology, Texas A&M University, Texas 77843-4466; k Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Kaiserslautern 67663, Germany; l Division of Environmental Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; m International Programme on Chemical Safety, World Health Organization, 1211 Geneva 27, Switzerland; n National Public Health Institute, Department of Environmental Health, FI-70701 Kuopio, Finland; o Environmental Chemistry, Umeå University, SE-901 87 Sweden; p National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709; and q School of Pharmacy and Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, 53705, USA

Received April 10, 2006; accepted May 20, 2006

In June 2005, a World Health Organization (WHO)-International Programme on Chemical Safety expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin-like compounds, including some polychlorinated biphenyls (PCBs), were reevaluated. For this reevaluation process, the refined TEF database recently published by Haws et al. (2006, Toxicol. Sci. 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 judgment, and point estimates. Previous TEFs were assigned in increments of 0.01, 0.05, 0.1, etc., but for this reevaluation, 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 (PeCDF) (TEF = 0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF = 0.03), octachlorodibenzo-p-dioxin and octachlorodibenzofuran (TEFs = 0.0003), 3,4,4',5-tetrachlorbiphenyl (PCB 81) (TEF = 0.0003), 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) (TEF = 0.03), and a 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 aryl hydrocarbon receptor 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'-TCB (PCB 37), polybrominated dibenzo-p-dioxins and dibenzofurans, mixed polyhalogenated dibenzo-p-dioxins and dibenzofurans, polyhalogenated naphthalenes, and polybrominated biphenyls. Concern was expressed about direct application of the TEF/total toxic equivalency (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 are 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 TEQ for body burden.

Key Words: dioxins; dibenzofurans; PCBs; TEFs; reevaluation; WHO.


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