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Overview of current TEFs as it relates to current PCB exposures: What is needed?
Citation:
KODAVANTI, PRASADA RAO S. AND L. S. BIRNBAUM. Overview of current TEFs as it relates to current PCB exposures: What is needed? . Presented at 5th PCB Workshop , Iowa City, IA, May 18 - 22, 2008.
Impact/Purpose:
A new scheme for toxic equivalence based on neurotoxic endpoints has been developed recently, which may be considered in addition to current TEFs based on AhR for the human health risk assessment of halogenated chemical mixtures.
Description:
The toxic equivalency factor (TEF) approach is one of the ways to assess the risk associated with exposure to complex mixture of polychlorinated biphenyls (PCBs) and structurally related chemicals. This method is based on mode of action with the assumption that all chemicals in the mixture mediate the adverse effects through the Aryl hydrocarbon receptor (AhR). The toxic potential of each chemical in the mixture is compared against tetrachloro-dibenzo-dioxin (TCDD), which is the most potent ligand for AhR, resulting in a TEF value. The toxic equivalency (TEQ) value for the mixture is derived from the addition of all the concentration-weighted TEF values for chemicals in that mixture. This approach serves well if all chemicals in the mixture have TCDD like effects. However, there are many reports showing that all of the nervous system effects are not mediated through AhR. Environmental mixtures are composed of many chemicals and dioxin-like chemicals are often a very small part of these mixtures. Among PCBs, non-dioxin like PCBs are >99% total mass. Although there are reports indicating different PCB congeners interact in an additive manner, some studies showed nonadditivity, both antagonistic and synergistic. Recent reports indicate that the critical effect for PCBs and other related chemicals is on the developing nervous system, where neurite outgrowth was affected at picomolar concentrations. Structurally related chemicals such as polybrominated diphenyl ethers that coexist with non-dioxin like PCBs exert effects on the nervous system at similar concentrations both in vitro and in vivo. Based on the critical effect on the developing nervous system and greater amounts of non-dioxin like chemicals in the mixtures, TEFs based on AhR activity may not be sufficient to predict the risk associated with exposure to PCBs and structurally related chemicals.