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describes the likelihood, based on scientific evidence, that the substance is a human carcinogen. A SF is then calculated that defines quantitatively the relationship between average lifetime dose and carcinogenic risk (EPA 1989b). - The slope factors are usually based on the results of animal studies. There is uncertainty whether animal carcinogens are also carcinogenic in humans. While many contaminant substances are carcinogenic in one or more animal species, only a small number of contaminant substances are known to be human carcinogens. The EPA assumes that humans are as sensitive to all animal carcinogens as the most sensitive animal species. This policy decision is designed to prevent underestimating risk and introduces the potential to overestimate carcinogenic risk (EPA 1989b). -- A number of mathematical models and procedures have been developed to extrapolate from carcinogenic responses observed at high doses in experimental animals to responses expected at the low doses humans may be exposed to. The EPA uses a conservative mathematical model, the linearized multistage model, for low-dose extrapolation. The V EPA further calculates the upper 95th percent confidence limit of the slope of the resulting dose-response curve. This SF value, expressed in units of(mg/kg-day)'', is used to convert the average daily intake of a contaminant, averaged over a lifetime, to a cancer risk. This represents an estimation of an upper-bound incremental lifetime _ probability that an individual will develop cancer as a result of exposure to a potential carcinogen. This model provides a conservative estimate of cancer risk at low doses, and is likely to overestimate the actual cancer risk. The EPA acknowledges that actual slope factors are likely to be between zero and the estimate provided by the linearized multistage model (EPA 1989b). The weight-of-evidence classifications and slope factors for the chemicals of concern are included in Tables 5-1 and 5-2. Oral RfDs and SFs were used to evaluate both the oral and dermal exposure routes. Data on oral absorption efficiency may be used to convert an administered-dose (oral) RfD or SF to an absorbed-dose (dermal) RfD or SF for use in calculation of risk from dermal absorption. However, because of the limited information on oral absorption efficiencies, conversion of administered-dose oral toxicity values to absorbed-dose values was not attempted. This approach could somewhat underestimate potential risk -- S:\LDC\YELLO.Rn May 4, 1995 5-5 r