Development of a refined database of mammalian relative potency estimates for dioxin-like compounds.

The toxic equivalency factor (TEF) approach has been widely accepted as the most feasible method available at present for evaluating potential health risks associated with exposure to mixtures of dioxin-like compounds (DLCs). The current mammalian TEFs for the DLCs were established by the World Health Organization (WHO) following the meeting of an international expert panel in June of 1997. The TEFs recommended by WHO were determined based on a consensus of scientific judgment and were presented as point estimates. However, the relative potency estimates (REPs) underlying the TEFs were derived from a heterogeneous data set and often span several orders of magnitude. In this article, we present a refined database of mammalian REPs that we believe will facilitate better characterization of the variability and uncertainty inherent in the data. The initial step involved reviewing the REP database used by the WHO panel during its review in 1997. A set of criteria was developed to identify REPs that were determined to be the most representative measure of a biological response and of adequate quality for use in quantitative analyses. REPs were determined to be inappropriate for use in quantitative analyses if any of the established exclusion criteria were met. Comparison of data records to the established exclusion criteria resulted in the identification of a substantial number of REPs believed to be inappropriate for use in quantitative analyses. Next, studies published after 1997 were added to the database. The availability of such a refined database will improve risk assessment for this class of compounds by including additional information from new studies and facilitating the use of quantitative approaches in the further development of TEFs.

[1]  G. Lucier,et al.  Receptor-mediated events and the evaluation of the Environmental Protection Agency (EPA) of dioxin risks. , 1995, Mutation research.

[2]  S. Safe,et al.  Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). , 1990, Critical reviews in toxicology.

[3]  J K Haseman,et al.  The comparative toxicity of chlorinated dibenzo-p-dioxins in mice and guinea pigs. , 1978, Toxicology and applied pharmacology.

[4]  P. Harper,et al.  The Ah receptor: mediator of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. , 1994, Toxicology letters.

[5]  George Eadon,et al.  Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures , 1986, Environmental health perspectives.

[6]  C. Schlatter,et al.  Subchronic relay toxicity study with a mixture of polychlorinated dioxins (PCDDs) and polychlorinated furans (PCDFs) , 1989 .

[7]  D. Barnes,et al.  Reexamination of data used for establishing toxicity equivalence factors (TEFs) for chlorinated dibenzo-p-dioxins and dibenzofurans (CDDs and CDFs) , 1989 .

[8]  A. Kozubík,et al.  Aryl hydrocarbon receptor-activating polychlorinated biphenyls and their hydroxylated metabolites induce cell proliferation in contact-inhibited rat liver epithelial cells. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  Abraham Nyska,et al.  Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds” , 2004, Environmental health perspectives.

[10]  D. Barnes,et al.  Interim procedures for estimating risks associated with exposures to mixtures of chlorinated dibenzodioxins and dibenzofurans (CDDs and CDFs) , 1986 .

[11]  L. Birnbaum,et al.  Toxicity equivalency factors for PCBs? , 1991, Quality assurance.

[12]  S. Safe,et al.  Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. , 1994, Critical reviews in toxicology.

[13]  L. Birnbaum The mechanism of dioxin toxicity: relationship to risk assessment. , 1994, Environmental health perspectives.

[14]  L. Kaminsky,et al.  Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the love canal. , 1989, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[15]  Linda S. Birnbaum,et al.  Toxic equivalency factors for dioxin-like PCBs , 1994 .

[16]  L. Birnbaum,et al.  Non-carcinogenic effects of TCDD in animals , 2000, Food additives and contaminants.

[17]  L. Birnbaum TEFs: A Practical Approach to a Real-World Problem , 1999 .

[18]  M. DeVito,et al.  Use of toxic equivalency factors for risk assessment for dioxins and related compounds. , 1995, Toxicology.

[19]  O. Hankinson The aryl hydrocarbon receptor complex. , 1995, Annual review of pharmacology and toxicology.

[20]  Robert L. Jones,et al.  Concentrations of environmental chemicals associated with neurodevelopmental effects in U.S. population. , 2005, Neurotoxicology.

[21]  P. Scott,et al.  The Use of Toxic Equivalency Factor Distributions in Probabilistic Risk Assessments for Dioxins, Furans, and PCBs , 2003, Journal of toxicology and environmental health. Part A.

[22]  V. K. Rowe,et al.  Toxicology of chlorinated dibenzo-p-dioxins. , 1973, Environmental health perspectives.

[23]  M. DeVito,et al.  Toxicology of Dioxins and Related Chemicals , 1994 .

[24]  Helmut Greim,et al.  The international toxicity equivalency factor (I-TEF) method of risk assessment for complex mixtures of dioxins and related compounds , 1990 .

[25]  R Rej,et al.  Subchronic oral toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the guinea pig: comparisons with a PCB-containing transformer fluid pyrolysate. , 1986, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[26]  S. Safe,et al.  Polychlorinated biphenyls: correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs). , 1985, Journal of toxicology and environmental health.

[27]  P. Dyke,et al.  Changes to the TEF schemes can have significant impacts on regulation and management of PCDD/F and PCB. , 2002, Chemosphere.

[28]  A. Szakolcai,et al.  Chlorinated dioxins and dibenzofurans in Ontario - analysing and controlling the risks: Development of scientific criteria document leading to multi-media standards for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo polychlorinated dibenzofurans (PCDFs) , 1986 .

[29]  D. Barnes,et al.  Interim procedures for estimating risks associated with exposures to mixtures of chlorinated dibenzo-p-dioxins and-dibenzofurans (CDDs and CDFs) and 1989 update , 1989 .

[30]  L. Birnbaum,et al.  Comparative ability of various PCBs, PCDFs, and TCDD to induce cytochrome P450 1A1 and 1A2 activity following 4 weeks of treatment. , 1993, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[31]  M. DeVito,et al.  Dose–Response Relationships for Polyhalogenated Dioxins and Dibenzofurans Following Subchronic Treatment in Mice , 1997 .

[32]  Safe,et al.  Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. , 1998, Environmental health perspectives.

[33]  Nigel J Walker,et al.  Evaluation of toxic equivalency factors for induction of cytochromes P450 CYP1A1 and CYP1A2 enzyme activity by dioxin-like compounds. , 2004, Toxicology and applied pharmacology.