Health Risks from Dioxin and Related Compounds Evaluation of the EPA Reassessment (2006) / Chapter Skim
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3 Toxic Equivalency Factors
3 Toxic Equivalency Factors
Pages 75-89
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From page 75... ...
, only 4 of the 122 previously defined as 2,3,7,8-tetrachlorodibenzo 1 The Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds (EPA 2003a, Part I; 2003b, Part II; 2003c, Part III)
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From page 76... ...
. Summation of the calculated TEQs for all active TCDD-related compounds in a sample extract yields the total TEQ for the specific sample extract.
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From page 77... ...
. Whether all TCDDrelated compounds produce these effects is unknown.
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From page 78... ...
. The committee agrees that end-point-specific TEFs should be used in those situations in which one is interested in assessing the effects of a sample on a specific end point; however, for general monitoring or screening approaches (that is, for TCDD-related compounds in food and environmental samples)
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From page 79... ...
TOXIC EQUIVALENCY FACTORS 79 end points should be considered, TEF values that are based on all end points should be used. Use of TEFs for DLC Body Burdens Perhaps the issue of greatest concern in this section of the Reassessment is whether the current WHO TEFs, which were developed to assess the relative toxic potency of a mixture to which an animal is directly exposed by dietary intake, are appropriate for the assessment of internal TEQ concentrations and potential toxic effects.
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From page 80... ...
, as has the ability of a lower-affinity synthetic PCDF, such as 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF) , to inhibit TCDD-induced CYP1A1, teratogenicity, immunotoxicity, and porphyria in rodent models in vivo (Astroff et al.
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From page 81... ...
In addition to ligand binding, the REP of TCDD and related compounds to induce AHR-dependent gene expression in human cells is also reduced by up to 10-fold (Roberts et al. 1990; Harper et al.
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From page 82... ...
, and some of these have also been shown to produce TCDD-like effects. However, the primary issue for the lack of consideration of these other TCDD-related compounds in the current assessment is that insufficient data are available on these chemicals, there are no currently determined or validated REPs and TEFs, and questions remain about the presence and persistence of these chemicals in the environment, food, and organisms.
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From page 83... ...
could be expected to produce AHR-dependent effects or inhibit the overall toxic and biological effects produced by a defined amount of TEQ calculated from TCDD-related compounds present in a sample extract. In most published studies, these metabolically labile non-DLC AHR agonists do not produce AHR-dependent toxicity; however, a few studies have reported the ability of some of these chemicals to produce TCDD-like toxic effects.
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From page 84... ...
Non-DLC AHR agonists could affect the TCDD-related compounds dose-response relationships for short biological responses (that is, gene induction) and contribute to an additive response for the end points.
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From page 85... ...
· Application of TEFs adequately predicted the increased incidence of liver tumors in rats (hepatocellular carcinoma and cholangiocarcinoma) induced by exposure to a mixture of TCDD, 3,3',4,4',5-PCB, and 2,3,4,7,8
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From page 86... ...
Consistent with the recommendations of the 2000 EPA SAB Panel, this committee also suggests that it would be appropriate for the Reassessment to note that end-point-specific TEFs/TEQs might be derived as data become available and that those specific values be used when that end point is being considered. It should also be made clear that general monitoring or screening approaches (that is, for TCDD-related compounds in food and
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From page 87... ...
· Rodent-to-human prediction. Although the REP of dioxins, other than TCDD, and DLCs in rodent models is predictive of REP in humans from a qualitative rank-order potency point of view, some species-specific differences in AHR ligand binding affinity of TCDD, other dioxins, and DLCs have been observed.
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From page 88... ...
The assumption that non-DLC AHR agonists with a short biological half-life do not interfere with DLC-dependent TEQ predictions for mixtures is controversial and remains to be confirmed. Although receptor binding kinetic evaluations suggest that these chemicals could interfere with TCDD, other dioxins, and DLCs if at high concentrations in blood and tissue, few of these metabolically labile non-DLC AHR agonists have been observed to directly produce AHR-dependent toxicity.
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From page 89... ...
TOXIC EQUIVALENCY FACTORS 89 tions and to what extent could or should internal WHO TEF factors be established in the future? EPA should consider the outcome of the IPCS TEF update meeting and incorporate the issues and changes into the Reassessment.
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