Slope Factors

Integrated Risk Infonnation System (IRIS) A USEPA data base containing verified RfDs and slope factors and up-to-date health risk and EPA regulatory information for numerous chemicals. IRIS is the USEPA s preferred source for toxicity information for Superfund studics/projects. 

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)... 

This section describes how the tj pes of to.xicity inforniation arc considered in the to.xicity assessment for carcinogenic effects. A slope factor and the accompanying weight of evidence determination are the toxicity data most commonly used to evaluate potential human carcinogenic risks. The methods the USEPA uses to derive these values arc outlined below. 

A slope factor is generated in the second part of the evaluation. Based on the evaluation that the chemical is a known or probable human carcinogen, a toxicity value that defines quantitatively the relationship between dose and response (i.e., the slope factor) is calculated. Slope factors are typically calculated for potential carcinogens in classes A, Bl, and B2. Quantitative estimation of slope factors for the chemicals in class C proceeds on a case-bycase basis. 

Generally, the slope factor is a plausible upper bound estimate of the probability of a response per unit intake of a ehemieal over a lifetime. The slope factor is used in risk assessments to estimate an upper-bound lifetime probability of an individual developing cancer as a result of e.xposure to a particular level of a potential carcinogen. Slope factors should always be accompanied by the weight-of-evidence classification to indicate the strength of the evidence that the agent is a human carcinogen. Calculational details are presented below. 

Because risk at low exposure levels is difficult to tneasure directly either by animal experiments or by epidemiologic studies, the development of a slope factor generally entails applying a model to the available data set and... 

To.xicity values for carcinogenic effects can be e.xprcsscd in several ways. The slope factor is usually, but not always, the upper 95th percent confidence limit of the slope of the dose-response curve and is e.xprcsscd as (mg/kg-day). If the extrapolation model selected is the linearized multistage model, this value is also known as the ql. That is ... 

Slope factor = risk per unit dose = risk per mg/kg-day... 

Where data permit, slope factors listed in IRIS are based on absorbed doses, although to date many of them ha c been based on administered doses. 

Toxicity alucs for carcinogenic effects also can be c.xprcsscd in terms of risk per unit concentration of the substance in the medium where human contact occurs. These measures, called unit risks, are calculated by dividing the slope factor by 70 kg and multiplying by the inhalation rate (20 m /day) or the water consumption rate (2 L/day), respecti ely, for risk associated with unit concentration in air or water. Where an absorption fraction less than 1.0 has been applied in deriving the slope factor, an additional conversion factor is necessary in the calculation of unit risk so that the unit risk will be on an administered dose basis. The standardized duration assumption for unit risks is understood to be continuous lifetime c.xposure. Hence, when there is no absorption conversion required ... 

What are the maximum number of excess lifetime cancer cases expected for a population of 5,000 adults with a daily intake of O.lOing of benzene The slope factor for benzene may be assumed to be 0.029 (mgAcg-day)". ... 

A slope factor and the accompanying weight of evidence determination are the toxicity data most commonly used to evaluate potential human... 

Because the slope factor is often an upper 95 percentile confidence limit of the probability of response based on experimental animal data used in tlie multistage model, tlie carcinogenic risk estimate will generally be an upper-bound estimate. Tliis means tliat tlie EPA is reasonably confident tliat tlie true risk will not exceed the risk estimate derived tlirough use of tliis model and is likely to be less than tliat predicted. 

For carcinogens, risks are estimated as the incremental probability of an indii idual developing ameer o er a lifetime as a result of exposure to the potential carcinogen. The slope factor (SF) converts estimated daily intakes averaged over a lifetime of exposure directly to incremental risk of an individual developing cancer. 

Chronic toxicity Mammalian systems Carcinogenicity Neurotoxicity De ve 1 opm e nta l/rep rod u cti ve toxicity Aquatic vertebrates and invertebrates Plants Mutagenicity, increased tumours Reproduction and growth Cancer slope factors Reference doses, and so on IC50, EC50... 

The pH (or pI) term of the Nemst equation contains the electrode slope factor as a linear temperature relationship. This means that a pH determination requires the instantaneous input, either manual or automatic, of the prevailing temperature value into the potentiometer. In the manual procedure the temperature compensation knob is previously set on the actual value. In the automatic procedure the adjustment is permanently achieved in direct connection with a temperature probe immersed in the solution close to the indicator electrode the probe usually consists of a Pt or Ni resistance thermometer or a thermistor normally based on an NTC resistor. An interesting development in 1980 was the Orion Model 611 pH meter, in which the pH electrode itself is used to sense the solution temperature (see below). 

The homologous series of (/ -methyibenzyl)alkylamines [387] indicates an interesting 8/log P ct plot, shown in Fig. 5.5. The slope factor of the smaller members of the series, —1.02, is larger than that of the phenol series. The value being near 1 indicates that log m is invariant with the octanol partition constant—the... 

Kinetic Constants and Model Parameters in the O Flaherty Model 2-7 Residence Times in the Biokinetic Module of the IEUBK Model 2-8 Kinetic Constants and Model Parameters in the Leggett Model 2-9 Summary of Blood Slope Factors from Various Environmental Media 2-10 Genotoxicity of Lead In Vivo 2-11 Genotoxicity of Lead In Vitro... 

Numerous studies have attempted to correlate environmental lead levels with blood lead levels (Table 2-9). Slope factors have been calculated which attempt to predict increases in PbB ( pg/dL) per unit lead concentration in environmental media (EPA 1986a, 1989g). The relationship between media concentration and PbB is curvilinear, such that the slopes decrease with increasing lead concentrations. 

Table 2-9. Summary of Blood Slope Factors from Various Environmental Media... 

Slope factors for the blood lead contribution from diet in adults can be obtained from an experimental study (Cools et al. 1976) and a duplicate diet study (Sherlock et al. 1982). These slope factors range from 0.027 to 0.034 pg/dL blood per pg lead intake/day (EPA 1986a). The data from the duplicate diet infant study by Ryu et al. (1983) were reanalyzed to derive a slope factor of 0.24 pg/dL blood per pg/day lead intake (EPA 1990e). 

Table 1. Summary of blood slope factors from various environmental media. 

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