The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds.
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.
Van den Berg
Martin
M
World Health Organization Collaborating Centre for Research on Environmental Health Risk Assessment and Institute for Risk Assessment Sciences, Science and University Medical Center, Universiteit Utrecht, The Netherlands. m.vandenberg@iras.uu.nl
Birnbaum
Linda S
LS
Denison
Michael
M
De Vito
Mike
M
Farland
William
W
Feeley
Mark
M
Fiedler
Heidelore
H
Hakansson
Helen
H
Hanberg
Annika
A
Haws
Laurie
L
Rose
Martin
M
Safe
Stephen
S
Schrenk
Dieter
D
Tohyama
Chiharu
C
Tritscher
Angelika
A
Tuomisto
Jouko
J
Tysklind
Mats
M
Walker
Nigel
N
Peterson
Richard E
RE
D000818:Animals; D001572:Benzofurans / Q000633:toxicity; D004147:Dioxins / Q000633:toxicity*; D023381:Endpoint Determination; D006801:Humans; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D011336:Probability; D018570:Risk Assessment; D014944:World Health Organization
D001572:Benzofurans; D004147:Dioxins; D011078:Polychlorinated Biphenyls; C038890:2,3,4,7,8-pentachlorodibenzofuran