TEF concept and ecology
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How should TEFs be applied in ecological examinations?
9.4.5. Examination of the TEF Methodology in Wildlife
Many wildlife species also exhibit toxic effects associated with exposure to halogenated aromatic hydrocarbons. Early life stage (ELS) or sac fry mortality in fish, characterized by edema, structural malformations, and growth reduction prior to fry mortality can be induced in trout species following exposure to dioxin-like PCDDs, PCDFs, and PCBs (Walker and Peterson, 1991). Binary combinations of a variety of PCDDs, PCDFs, and both dioxin and non-dioxin-like PCB congeners injected into fertilized trout eggs were also capable of inducing ELS mortality, with the majority of interactions between the congeners described as strictly additive (Zabel et al., 1995). When a synthetic complex mixture of PCDDs, PCDFs, and PCBs, in congener ratios that approximated Great Lakes fish residues, was tested in the ELS mortality assay, the lethal potency observed for the mixture, compared to TCDD, deviated less than twofold from an additivity approach (Walker et al., 1996). Recently, the TCDD TEQ of an environmental complex mixture of PCDDs, PCDFs, and PCBs extracted from lake trout and applied to the ELS bioassay could also be predicted by an additivity approach (Tillitt and Wright, 1997). These results suggest that additional halogenated aromatic compounds, including non-dioxin-like PCBs, present in fish do not significantly detract from an additivity response for this AhR-mediated event.
There are also numerous studies that have examined the effects of environmental mixtures in marine mammals and avian species (Ross, 2000; Giesy and Kannan, 1998; Ross et al., 1996; Shipp et al., 1998a,b; Restum et al., 1998; Summer et al., 1996a,b). Ross and colleagues examined captive harbor seals fed herring from either the Atlantic Ocean (low levels of PCDDs/PCDFs/PCBs) or the Baltic Sea (high levels of PCDDs/PCDFs/PCBs). The seals fed herring from the Baltic Sea displayed immunotoxic responses including impaired natural killer cell activity and antibody responses to specific antigens. These effects were correlated with the TEQ concentrations in the herring. Using mink as a model, Aulerich, Bursian, and colleagues have also examined the TEF methodology. Minks were fed diets containing carp from Saginaw Bay to provide exposures of 0.25, 0.5, or 1 ppm PCB in the diet. In a series of reports, the authors demonstrated that the diet induced dioxin-like effects ranging from enzyme induction to reproductive and developmental effects, and that these effects were correlated with the dietary intake of TEQs (Giesy and Kannan, 1998). Similar studies in White Leghorn hens also demonstrated that the TEQ approach provided accurate estimates of the potency of the mixtures (Summer et al., 1996).
In summary, current experimental evidence suggests that for PCDDs, PCDFs, coplanar dioxin-like PCBs, and strictly AhR-mediated events, the concept of TEF additivity adequately estimates the dioxin-like toxicity of either synthetic mixtures or environmental extracts, despite the variations in relative contributions of each congener. Addition of the more prevalent mono-and di-ortho-substituted PCBs to a mixture, at least in the case of environmental extracts and wildlife, does not seem to significantly detract from this assumption of additivity. Interactions other than additivity (antagonism, synergism) have been observed with a variety of effects (teratogenicity, immunotoxicity, hepatic porphyrin accumulation, thyroid hormone metabolism) in both binary combinations and complex synthetic mixtures of dioxin and partial or non-Ah receptor agonists (commercial PCBs, PCB 153). However, it appears that at these high-dose exposures, multiple mechanisms of action not under the direct control of the Ah receptor are responsible for these nonadditive effects.
Additional research efforts should focus on complex mixtures common to both environmental and human samples and the interactions observed with biological and toxicological events known to be under Ah receptor control. In the interim, the additive approach with TEFs derived by scientific consensus of all available data appears to offer a good estimation of the dioxin-like toxicity potential of complex mixtures, keeping in mind that other effects may be elicited by non-dioxin-like components of the mixture.
- TEF concept
- Ah receptor ligands
- TEF concept in environmental health assessment
- TEF concept and uncertainty analysis
- Additivity of TEFs
- TEF concept and ecology
- TEF concept and Ah receptor
- Estimating TEF values