Toxicity equivalent quotients

Although activation of the AHR by DLCs is a key event, mechanistic data indicate that AHR-mediated responses are not well conserved across species, with lower sensitivity in humans. A TEF value for a DLC based on rodent data may overestimate the potency of a DLC in humans, and this has not been considered in the current risk assessment of DLCs. Thus, the current TEF-Toxic Equivalency Quotient scheme tends to compound the conservative estimates of risk that exist within standard risk assessment approaches. Moreover mechanistic differences will now be considered by US EPA in the risk assessment of chemical carcinogens. The mechanistic data currently available for receptor-mediated DLCs and PPs clearly indicate that humans respond differently to these two classes of rodent carcinogens, and these data will need to be incorporated into cancer risk assessments for these chemicals. Full appreciation of the species differences in these receptor mechanisms will require continued development and refinement of models such as primary... 

PM10 is the particulate matter less than 10 microns in diameter, and TEQ is the Toxic Equivalent Quotient. 

Eadon et al.14 devised the toxic equivalency approach. For this, specific dioxin-like compounds are assigned a potency or toxic equivalency factor (TEF) relative to TCDD, which usually has been found to be the most toxic dioxin-like compound and assigned a value of 1.0. The concentration of a specific compound in a sample can then be expressed as a toxic equivalent concentration or quotient (TEQ) by multiplying the concentration of the compound as determined by analytical chemistry techniques by its TEF. Next, the dioxin-like compounds in a sample are assumed to act in an additive manner. Therefore, the TEQ for the sample can be determined by adding together the TEQs for each dioxin-like compound in the sample and the final TEQ can be used in risk assessment. 

The term toxic unit (TU) plays an important role in mixture concentration-response analysis. It is defined as the actual concentration of a chemical in the mixture divided by its effect concentration (e.g., c/EC50 Sprague 1970). The toxic unit is equivalent to the hazard quotient (HQ), which is used for calculating the hazard index (HI Hertzberg and Teuschler 2002). The term hazard quotient is generally used more in the context of risk assessment (see Chapter 5 on risk assessment), and the term toxic unit is used more in the context of concentration-response analysis, and therefore the latter term is used here. Toxic units are important for 2 reasons. First, toxic units are the core of the concept of concentration addition concentration addition occurs if the toxic units of the chemicals in a mixture that causes 50% effect sum up to 1. Second, toxic units can help to determine which concentrations of the chemicals to test when a mixture experiment needs to be designed. 

In the RPF method (eqn (1)), the user must identify the constraints of the application of a set of RPFs. For example, the health effect, dose range of component doses, route(s) of exposure, and dura-tion(s) of exposure for which the RPFs can be applied must be specified (e.g., a set of RPFs may be constrained to oral exposures and not be used for exposures to the same mixture through the inhalation route). To apply the method, an RPF is estimated for each mixture component the RPF estimates the toxicity of the component relative to that of the IC. RPFs commonly are estimated from a ratio of equally toxic doses of the individual dose-response functions for the component and the IC. For example, the quotient of the effective dose at which ten percent of a test population exhibits an effect (EDio) of the IC and the component could serve as a value for the component s RPF obviously, the RPF for the IC equals 1. The index chemical equivalent dose of an individual component is the product of the component dose and the RPF of the component. These equivalent doses are summed across all components. The risk posed by the mixture is estimated by comparing the summed index chemical equivalent doses of the mixture to the dose-response function of the IC ... 

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