Potency factor

Carcinogen Potency Factor (CPF) A CPF is the slope of the dose-response cun e at very low exposures. The dimensions of a CPF, are expressed as the iin erse of daily dose (mg/kg-day)". ... 

Slope Factor The slope factor is used to estimate an upper-bound lifetime probabilit) of an individual dc cloping cancer as a result of exposure to a particular le cl of a potential carcinogen. Also sec Carcinogen Potency Factor (CPF)... 

Determine the action level in pg/iiv for an 80 kg person with a life expectancy of 70 years exposed to benzene over a 15-year period. The "acceptable risk is one incident of cancer per 1 million persons or lO ". Assume a breathing (intake) rate of 15 m /d and an absorption factor of 75%. The potency factor for benzene is 1.80 (mg/kg-d)." ... 

The 95% confidence limits of the estimate of the linear component of the LMS model, /, can also be calculated. The 95% upper confidence limit is termed qi and is central to the US-EPA s use of the LMS model in quantitative risk assessment, as qi represents an upper bound or worst-case estimate of the dose-response relationship at low doses. It is considered a plausible upper bound, because it is unlikely that the tme dose-response relationship will have a slope higher than qi, and it is probably considerably lower and may even be zero (as would be the case if there was a threshold). Lfse of the qj as the default, therefore, may have considerable conservatism incorporated into it. The values of qi have been considered as estimates of carcinogenic potency and have been called the unit carcinogenic risk or the Carcinogen Potency Factor (CPF). 

Studies in rats reported renal tubular adenomas and adenocarcinomas in male and female animals at doses of 20 mg/kg/day (Kociba et al. 1977a). Metastasis to the lungs was observed. Combined incidences of renal tubular neoplasms in males (9/39, 23%) and in females (6/40, 15%) increased (p <0.05) over controls (males-1/90, females-0/90, 0%). The tumor incidence was not increased in the 0.2 and 2 mg/kg/day dose groups but there were some indications of hyperplasia in animals exposed to 2 m /kg/day. The EPA (1990f) evaluated these data and calculated a human potency factor of 7.8x10 (mg/kg/day) (qi ), representing 95% upper confidence limit of extra lifetime human risk. Based on this value, cancer risk levels of 10, 10, and 10 correspond to exposures of 0.001, 0.0001, 0.00001 mg/kg/day. 

California Air Resources Board/Office of Environmental Health Hazard Assessment, Benzol a] pyrene as a Toxic Air Contaminant (1994) Office of Environmental Health Hazard Assessment/California Environmental Protection Agency, Air Toxics Hot Spot Program Risk Assessment Guideline, Part II Technical Support Document for Describing Available Cancer Potency Factors (1998) Collins et al. (1998). 

Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Air Toxics Hot Spot Program Risk Assessment Guideline Part II Technical Support Document for Describing Available Cancer Potency Factors, 1998. 

Among the many different types of ARARs are ambient or chemical-specific requirements, which can be levels set by other laws, such as MCLs, National Ambient Air Quality Standards (NAAQS), or CWA, CAA, and TSCA regulations, and the long-term remedial action would have to meet those goals. Because not that many ambient or chemical-specific requirements have been established, other types of ARARs must usually be identified. An alternative is for the USEPA to use carcinogenic potency factors or reference doses to set the proper level of treatment. It must be remembered, though, that each ARAR is specific to the remedial activity and not the pollutant. 

Based on the evidence reviewed above, EPA has concluded that BCME is a known human carcinogen (EPA Group A). Employing the data of Kuschner et al. (1975), EPA (1988) has calculated an upper bound cancer potency factor (q ) of 220 (mg/kg/day)1. Assuming that a 70-kg adult inhales 20 m3/day, the concentrations of BCME associated with upper bound human risk levels of 10 4, 10 5, 10 6 and 10"7 are 3.4 x 10"7, 3.4 x 10"8, 3.4 x 10 9 and 3.4 x 10 10 ppm, respectively. These values, and doses which have been observed to cause cancer, are plotted in Figure 2-1. 

In general, the relationship between dose and response can be represented by a variety of functional forms. At low doses of substances that cause stochastic effects, the dose-response relationship usually is assumed to be linear and, thus, can be expressed as a single probability coefficient. This coefficient is frequently referred to as a risk (or potency factor or unit risk factor or slope factor) in the literature. However, it is really the response (consequence) resulting from a dose of a hazardous substance, and it should not be confused with risk as defined and used in this Report. 

Equation 4.2 allows the direct calculation (prediction) of an ECx value for the mixture. In general, no explicit formulation of the CA-expected mixture effect E(cMb) is possible direct calculations are restricted to the level of effect concentrations (ECx values) (Faust et al. 2001). Only in the so-called simple similar action cases can CA-expected mixture effects be directly calculated. Since the Saaresilka agreement (consensus agreement on mixture toxicology terminology Greco et al. 1992) simple similar action may be considered a special case of CA, which assumes that the individual curves of the components are concentration parallel that is, there is an effect-level independent constant potency factor between the individual concentration-response curves. On this condition, the CA-expected mixture effect can be explicitly formulated as... 

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. 

TEF Toxicity equivalency factor. Ratio of the toxicity of a chemical to that of another structurally related chemical (or index compound) chosen as a reference. TEFs are toxicity potency factors used to evaluate the toxicities of highly variable mixtures of dioxin-like compounds. The most toxic members, 2,3,7,8-TCDD and 1,2,3,7,8-pentachlorodibenzo-p-dioxin, are... 

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. 

Davidson KA, Faust RA. 1996. Oral carcinogen potency factors for benzene and some of its metabolites. Fund Appl Toxicol Suppl. The Toxicologist 30(1) 114. 

Phenylephrine and entry 1, 30 and 10p,g/kg, respectively, were introduced into the vena femoralis through a polyethylene cannula. Compared with phenylephrine, the experimental agent exhibited a potency factor 2.73 times greater with regard to the contraction of the urethra and with a duration longer by a factor of 4.3. Moreover, the increase in blood pressure associated with entry 1 was only 1.39 times that of phenylephrine. Testing results are provided in Table 2. 

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