BOX 6-6
Derivation of Cancer Slope Factors

CSFs can be derived using a multistage model of cancer (available through EPA’s Benchmark Dose Modeling software), where the quantal relationship of tumors to dose is plotted. A point of departure, or dose that falls at the lower end of a range of observation for a tumor response, is estimated, and a straight line is plotted from the lower bound to zero. The below figure illustrates a linear cancer risk assessment (Donohue and Orme-Zavaleta, 2003). The CSF is the slope of the line (cancer response/dose) and is the tumorigenic potency of a chemical.

The CSF can be used as the basis for deriving an acceptable level of chemical contaminant in reclaimed water, using the following equation:


where the acceptable risk level generally equals 10-6, and drinking water intake is assumed to be 2 L/d.


Example cancer risk extrapolation, using the linear dose-response model. The CSF is the slope of the line (i.e., cancer response/dose) and represents the tumorigenic potency of a chemical.

NOTES: MoE = margin of exposure; ED10 = effective dose at 10 percent response; LED10 = lower 95th confidence interval of ED10.
SOURCE: Adapted from Donohue and Orme-Zavaleta (2003)

Risk Characterization Given Lack of Data

For many chemicals, dose-response information is unavailable. Nonetheless, communities still need to make decisions on water reuse projects in the absence of such data. In this section, frameworks for providing information on risk in absence of dose-response data are discussed.

Numerous organic and inorganic chemicals have been identified in reclaimed water and waters that receive wastewater effluent discharges, and only a limited number of these chemicals are actually regulated in water supplies. Current regulatory testing protocols address only one chemical at a time, leaving a gap in our understanding of the potential adverse effects of chronic, low-level exposure to a complex mixture of chemicals. A mixture of chemicals may result in toxicity that is additive (i.e., reflecting the sum of the toxicity of all individual components), antagonistic (i.e., toxicity is less than that of an individual component), potentiated (i.e., toxicity is greater than that of an individual component), or synergistic (i.e., with toxicity that is greater than additive). Of particular concern are chemicals that are mutagenic or carcinogenic and share similar modes of action. As with other types of exposures, in the case of reclaimed water, multiple chemicals may be present

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