Toxic equivalency factor (TEF) expresses the toxicity of dioxins, furans and PCBs in terms of the most toxic form of dioxin, 2,3,7,8-TCDD. The toxicity of the individual congeners may vary by orders of magnitude. With the TEFs, the toxicity of a mixture of dioxins and dioxin-like compounds can be expressed in a single number – the toxic equivalency (TEQ). It is a single figure resulting from the product of the concentration and individual TEF values of each congener. The TEF/TEQ concept has been developed to facilitate risk assessment and regulatory control. While the initial and current set of TEFs only apply to dioxins and dioxin-like chemicals (DLCs), the concept can theoretically be applied to any group of chemicals satisfying the extensive similarity criteria used with dioxins, primarily that the main mechanism of action is shared across the group. Thus far, only the DLCs have had such a high degree of evidence of toxicological similarity. There have been several systems over the years in operation, such as the International Toxic Equivalents for dioxins and furans only, represented as I-TEQDF, as well as several country-specific TEFs. The present World Health Organization scheme, represented as WHO-TEQDFP, which includes PCBs is now universally accepted.
Chemical mixtures and additivity Humans and wildlife are rarely exposed to solitary contaminants, but rather to complex mixtures of potentially harmful compounds. Dioxins and DLCs are no exception. This is important to consider when assessing toxicity because the effects of chemicals in a mixture are often different from when acting alone. These differences can take place on the chemical level, where the properties of the compounds themselves change due to the interaction, creating a new dose at the target tissue and a quantitatively different effect. They may also act together (simple similar action) or independently on the organism at the receptor during uptake, when transported throughout the body, or during metabolism, to produce a joint effect. Joint effects are described as being additive (using dose, response/risk, or measured effect), synergistic, or antagonistic. A dose-additive response occurs when the mixture effect is determined by the sum of the component chemical doses, each weighted by its relative toxic potency. A risk-additive response occurs when the mixture response is the sum of component risks, based on the probability law of independent events. An effect-additive mixture response occurs when the combined effect of exposure a chemical mixture is equal to the sums of the separate component chemical effects, e.g., incremental changes in relative liver weight. Synergism occurs when the combined effect of chemicals together is greater than the additivity prediction based on their separate effects. Antagonism describes where the combined effect is less than the additive prediction. Clearly it is important to identify which kind of additivity is being used. These effects reflect the underlying modes of action and mechanisms of toxicity of the chemicals. Additivity is an important concept here because the TEF method operates under the assumption that the assessed contaminants are dose-additive in mixtures. Because dioxins and DLCs act similarly at the AhR, their individual quantities in a mixture can be added together as proportional values, i.e. TEQs, to assess the total potency. This notion is fairly well supported by research. Some interactions have been observed and some uncertainties remain, including application to other than oral intake.
TEF Exposure to environmental media containing 2,3,7,8-TCDD and other dioxins and dioxin-like compounds can be harmful to humans as well as to wildlife. These chemicals are resistant to metabolism and biomagnify up the food chain. Toxic and biological effects of these compounds are mediated through the aryl hydrocarbon receptor (AhR). Oftentimes results of human activity leads to instances of these chemicals as mixtures of DLCs in the environment. The TEF approach has also been used to assess the toxicity of other chemicals including PAHs and xenoestrogens. The TEF approach uses an underlying assumption of additivity associated with these chemicals that takes into account chemical structure and behavior. For each chemical the model uses comparative measures from individual toxicity assays, known as relative effect potency (REP), to assign a single scaling factor known as the TEF.
TCDD 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the reference chemical to which the toxicity of other dioxins and DLCs are compared. TCDD is the most toxic DLC known. Other dioxins and DLCs are assigned a scaling factor, or TEF, in comparison to TCDD. TCDD has a TEF of 1.0. Sometimes PCB 126 is also used as a reference chemical, with a TEF of 0.1.
Determination of TEF TEFs are determined using a database of REPs that meet WHO established criteria, using different biological models or endpoints and are considered estimates with an order of magnitude of uncertainty. The characteristics necessary for inclusion of a compound in the WHO's TEF approach include:
Structural similarity to polychlorinated dibenzo-p-dioxins or polychlorinated dibenzofurans Capacity to bind to the aryl hydrocarbon receptor (AhR) Capacity to elicit AhR-mediated biochemical and toxic responses Persistence and accumulation in the food chain All viable REPs for a chemical are compiled into a distribution, and the TEF is selected based on half order of magnitude increments on a logarithmic scale. The TEF is typically selected from the 75th percentile of the REP distribution in order to be protective of health.
In vivo and in vitro studies REP distributions are not weighted to give more importance to certain types of studies. Current focus of REPs is on in vivo studies rather than in vitro. This is because all types of in vivo studies (acute, subchronic, etc.) and different endpoints have been combined, and associated REP distributions are shown as a single box plot.
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