Risk assessment relative potency factor

Figure 5.12 The principle of tiering in risk assessment simple questions can be answered by simple methods that yield conservative answers, and more complex questions require more sophisticated methods, more data, and more accurate risk predictions. PEC = Predicted Environmental Concentration, PNEC = Predicted No Effect Concentration, HI = Hazard Index, CA = Concentration Addition, RA = Response Addition, TEF = Toxicity Equivalency Factor, RPF = Relative Potency Factor, MOA = Mode of Action, PBPK = Physiologically Based Pharmacokinetic, BRN = Biochemical Reaction Network.

Carcinogenic Effects. Specific hydrocarbon indicator compounds that have EPA cancer risk estimates are assessed these are benzene and benzo(a)pyrene. EPA relative potency factors can be used for benz(a)anthracene, indeno(l,2,3-cd)pyrene, dibenz(a,h)anthracene, chrysene, benzo(b)fluoranthene, and benzo(k)fluoranthene. 

A method for assessing the potential carcinogenic effects of these PAHs would be to use the EPA cancer risk levels for benzo(a)pyrene and the relative potency factors for the individual PAHs (Table 6-7). 

EPA used the relative potency factor (RPF) method in its cumulative hazard assessment of the OPs. The RPF method is based on the assumption of dose additivity, Dose additivity is the agency s assumption when evaluating the joint risk of chemicals that are toxicologically similar and act at the. same target site (EPA, 2001c). Briefly, with the RPF approach, the toxic potency of each chemical is first determined. One chemical, called the index chemical, is then selected. The index chemical provides the basis for comparison. Relative potency is determined by converting the toxic potency of each chemical into toxic equivalents of the index chemical. 

TABLE 4. OP Relative Potency Factors (Methamidophos-Equivalents) Estimated for EPA s Cumulative Risk Assessment for the Oral, Dermal, and Inhalation Routes of Exposure ... 

The U.S. FDA reported ° the relative testicular toxicity of MEHP to DEHP as relative potency factor (RPF) = 10 that is, MEHP toxicity is 10 times higher than DEHP toxicity. The U.S. EPA performed risk assessment of a mixture using RPF, which is also known as the toxic equivalency factor (TEF), and the concentration of the mixture of MEHP and DEHP is calculated with the following formula ... 

What could be done to better assess immunomodulatory effects in NHP that will be predictive of the outcome in humans One important consideration comes back to the relevance of the animal species. Not only should the binding affinity and functionality at the target be considered, but the relative potency as well can be a critical factor. Understanding the dose-concentration-response relationships for receptor occupancy, receptor modulation and functionality, and target expression and distribution in comparison to normal human subjects and in disease state can help us to better assess risk to patients. 

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. 

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