Relative potency factor

Additivity and no interactions. Additivity concepts that explain a shared adverse effect across chemicals include dose or concentration addition, which assumes chemicals share a common toxic MOA, and RA, which assumes chemicals act by toxicologically (and thus also statistically) independent MOA. There is also a body of research on the use of statistical dose-response modeling of empirical data to examine the joint toxic action of defined mixtures where the claim is that MOA assumptions are not necessary (Gennings et al. 2005). Dose addition methods scale the component doses for relative toxicity and estimate risk using the total summed dose, for example, using relative potency factors (RPFs), toxicity equivalency factors (TEFs), or a hazard index (HI). In contrast, RA (also named independent action ) is... 

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.

RPF Relative potency factor. A factor that expresses the toxic potency of a mixture component relative to an index compound. In the RPF approach, RPF values of mixture components are summed and the risk of the whole mixture is estimated using dose-response data of the index compound. 

USEPA] US Environmental Protection Agency. 2003b. Developing relative potency factors for pesticide mixtures biostatistical analyses of joint dose-response. EPA/600/R-03/052, ORD/NCEA. Cincinnati (OH) US Environmental Protection Agency. 

Component methods include those based on the assumption of response addition (e.g., addition of probabilistic cancer risks) or dose addition (e.g., relative potency factors (RPFs), hazard indexes (HI)). The advantages of component methods include an ability to utilize single chemical exposure and dose-response information to estimate a mixture risk and the flexibility to compare mixtures containing the same chemicals, but in different concentrations and proportions. 

Two other methods are based on the tenets of dose addition but differ from the HI approach. Those are the relative potency factor (RPF) and the toxicity equivalent factor (TEF) approaches. 

Carcinogenic Effects. Specific petroleum hydrocarbon indicator compounds that have EPA cancer potency factors 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). 

Table 1. Relative Potency Factors Used in Estimating...

Relative potency factor for the most toxic 2,3,7,8-subs tituted isomer. 

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 ... 

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