ToxSci Advance Access published online on July 7, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl055
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 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
* To whom correspondence should be addressed. 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 (PeCDF) (TEF=0.3), 1,2,3,7,8-pentachlorodibenzofuran (PeCDF) (TEF=0.03), octachlorodibenzo-p-dioxin (OCDD) and octachlorodibenzofuran (OCDF) (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 nondioxin-like aryl hydrocarbon 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'-TCB (PCB 37), polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans (PBDFs), mixed polyhalogenated dibenzo-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.
Received April 10, 2006
Accepted May 20, 2006
Forum
The 2005 World Health Organization Re-evaluation of Human and Mammalian Toxic Equivalency Factors for Dioxins and Dioxin-like Compounds
Martin van den Berg 1 *,
Linda S. Birnbaum 2,
Michael Denison 3,
Mike De Vito 2,
William Farland 4,
Mark Feeley 5,
Heidelore Fiedler 6,
Helen Hakansson 7,
Annika Hanberg 7,
Laurie Haws 8,
Martin Rose 9,
Stephen Safe 10,
Dieter Schrenk 11,
Chiharu Tohyama 12,
Angelika Tritscher 13,
Jouko Tuomisto 14,
Mats Tysklind 15,
Nigel Walker 16,
and
Richard E. Peterson 17
2 USEPA, ORD NHEERL ETD, MD-B143-01,109 TW Alexander Drive, Research Triangle Park, NC 27709, USA
3 University of California Davis, Dept of Environmental Toxicology, One Shields Avenue 4241 Meyer Hall, Davis, CA 95616-8501, USA
4 Office of Research and Development, US Environmental Protection Agency (EPA), 1200 Pennsylvania Ave., NW, Washington DC 20460, USA
5 Chemical Health Hazard Assessment Division, Bureau of Chemical Safety, Health Canada, Sir Frederick Banting, Bldg. Postal Locator: 2204D1, Tunney's Pasture, Ottawa, ON K1A OL2, Canada
6 UNEP Chemicals, International Environment House, 11-13, chemin des Anémones, CH-1219 Châtelaine (GE), Switzerland
7 Institute of Environmental Medicine, Karolinska Institutet, Unit of Environmental Health Risk Assessment, Box 210, Nobels võg 13, S-171 77 Stockholm, Sweden
8 ChemRisk, 8024 Messa Dr., #126,Austin, Texas, USA
9 Central Science Laboratory, Sand Hutton, YO41 1LZ York, United Kingdom
10 Texas A&M University, Veterinary Physiology and Pharmacology, MS 4466 College Station, TX 77843-4466, USA
11 University of Kaiserslautern, Dept of Food Chemistry and Environmental Toxicology, Erwin-Schrodinger-Strasse 52, Kaiserslautern 67663, Germany
12 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
13 International Programme on Chemical Safety, World Health Organization, 1211 Geneva 27, Switzerland
14 National Public Health Institute, Dept of Environmental Health, P.O. Box 95, FI-70701 Kuopio, Finland
15 Environmental Chemistry, Umeå University, SE-901 87 Sweden
16 National Institute of Environmental Health Sciences, 111 TW Alexander Drive, P.O. Box 12233 Mail Drop EC-34, Research Triangle Park, NC 27709, USA
17 School of Pharmacy and Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, 53705, USA
Martin van den Berg, E-mail: m.vandenberg{at}iras.uu.nl
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. D. Burgoon, Q. Ding, A. N'jai, E. Dere, A. R. Burg, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Automated Dose-Response Analysis of the Relative Hepatic Gene Expression Potency of TCDF in C57BL/6 Mice Toxicol. Sci., November 1, 2009; 112(1): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Flippin, J. M. Hedge, M. J. DeVito, G. A. LeBlanc, and K. M. Crofton Predictive Modeling of a Mixture of Thyroid Hormone Disrupting Chemicals That Affect Production and Clearance of Thyroxine International Journal of Toxicology, September 1, 2009; 28(5): 368 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhang, P. Lei, X. Liu, X. Li, K. Walker, L. Kotha, C. Rowlands, and S. Safe The aryl hydrocarbon receptor as a target for estrogen receptor-negative breast cancer chemotherapy Endocr. Relat. Cancer, September 1, 2009; 16(3): 835 - 844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jiang, D. R. Bell, S. Clode, M. Q. Fan, A. Fernandes, P. M. D. Foster, G. Loizou, A. MacNicoll, B. G. Miller, M. Rose, et al. A Truncation in the Aryl Hydrocarbon Receptor of the CRL:WI(Han) Rat Does Not Affect the Developmental Toxicity of TCDD Toxicol. Sci., February 1, 2009; 107(2): 512 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Simon, C. R. Kirman, L. L. Aylward, R. A. Budinsky, J. C. Rowlands, and T. F. Long Estimates of Cancer Potency of 2,3,4,7,8-Pentachlorodibenzofuran Using Both Nonlinear and Linear Approaches Toxicol. Sci., December 1, 2008; 106(2): 519 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Billiard, J. N. Meyer, D. M. Wassenberg, P. V. Hodson, and R. T. Di Giulio Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment Toxicol. Sci., September 1, 2008; 105(1): 5 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Zwiernik, S. Bursian, L. L. Aylward, D. P. Kay, J. Moore, C. Rowlands, K. Woodburn, M. Shotwell, J. S. Khim, J. P. Giesy, et al. Toxicokinetics Of 2,3,7,8-TCDF and 2,3,4,7,8-PeCDF in Mink (Mustela vison) at Ecologically Relevant Exposures Toxicol. Sci., September 1, 2008; 105(1): 33 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chevrier, B. Eskenazi, N. Holland, A. Bradman, and D. B. Barr Effects of Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides on Thyroid Function during Pregnancy Am. J. Epidemiol., August 1, 2008; 168(3): 298 - 310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N'Jai, D. R. Boverhof, E. Dere, L. D. Burgoon, Y. S. Tan, J. C. Rowlands, R. A. Budinsky, K. E. Stebbins, and T. R. Zacharewski Comparative Temporal Toxicogenomic Analysis of TCDD- and TCDF-Mediated Hepatic Effects in Immature Female C57BL/6 Mice Toxicol. Sci., June 1, 2008; 103(2): 285 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Silkworth, E. A. Carlson, C. McCulloch, K. Illouz, S. Goodwin, and T. R. Sutter Toxicogenomic Analysis of Gender, Chemical, and Dose Effects in Livers of TCDD- or Aroclor 1254-Exposed Rats Using a Multifactor Linear Model Toxicol. Sci., April 1, 2008; 102(2): 291 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Kopec, D. R. Boverhof, L. D. Burgoon, D. Ibrahim-Aibo, J. R. Harkema, C. Tashiro, B. Chittim, and T. R. Zacharewski Comparative Toxicogenomic Examination of the Hepatic Effects of PCB126 and TCDD in Immature, Ovariectomized C57BL/6 Mice Toxicol. Sci., March 1, 2008; 102(1): 61 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Wilkes, B. S. Hass, D. A. Buzatu, L. M. Pence, J. C. Archer, R. D. Beger, L. K. Schnackenberg, M. K. Halbert, L. Jennings, and R. L. Kodell Modeling and Assaying Dioxin-Like Biological Effects for both Dioxin-Like and Certain Non-Dioxin-Like Compounds Toxicol. Sci., March 1, 2008; 102(1): 187 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Bordajandi and M. J. Gonzalez Enantiomeric Fraction of Selected Chiral Polychlorinated Biphenyls in Cow, Goat, and Ewe Milk and Dairy Products by Heart-Cut Multidimensional Gas Chromatography: First Results J Dairy Sci, February 1, 2008; 91(2): 483 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yoshizawa, A. Heatherly, D. E. Malarkey, N. J. Walker, and A. Nyska A Critical Comparison of Murine Pathology and Epidemiological Data of TCDD, PCB126, and PeCDF Toxicol Pathol, December 1, 2007; 35(7): 865 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Burgoon Clearing the Standards Landscape: the Semantics of Terminology and their Impact on Toxicogenomics Toxicol. Sci., October 1, 2007; 99(2): 403 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Bell, S. Clode, M. Q. Fan, A. Fernandes, P. M. D. Foster, T. Jiang, G. Loizou, A. MacNicoll, B. G. Miller, M. Rose, et al. Relationships between Tissue Levels of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), mRNAs, and Toxicity in the Developing Male Wistar(Han) Rat Toxicol. Sci., October 1, 2007; 99(2): 591 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Bell, S. Clode, M. Q. Fan, A. Fernandes, P. M. D. Foster, T. Jiang, G. Loizou, A. MacNicoll, B. G. Miller, M. Rose, et al. Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Developing Male Wistar(Han) Rat. II: Chronic Dosing Causes Developmental Delay Toxicol. Sci., September 1, 2007; 99(1): 224 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Brown Jr, B. A. Mayes, J. B. Silkworth, and S. B. Hamilton Polychlorinated Biphenyls Modulated Tumorigenesis in Sprague Dawley Rats: Correlation with Mixed Function Oxidase Activities and Superoxide (O2* ) Formation Potentials and Implied Mode of Action Toxicol. Sci., August 1, 2007; 98(2): 375 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Okey An Aryl Hydrocarbon Receptor Odyssey to the Shores of Toxicology: The Deichmann Lecture, International Congress of Toxicology-XI Toxicol. Sci., July 1, 2007; 98(1): 5 - 38. [Abstract] [Full Text] [PDF]
|
|