7.4 Risk assessment methodology for conventional and alternative  (Page 5/17)

• Cancer Slope Factor (CSF) for oral/dermal pathway or Unit Risk Factor (URF) for inhalation pathway – Carcinogens: Unlike the noncarcinogens, carcinogens assumed to be non-threshold chemicals based on the Environmental Protection Agency (EPA) assumption that a small number of molecular events can evoke changes in a single cell that can lead to uncontrolled cellular proliferation and eventually to cancer. In deriving slope factors, firstly, an appropriate dose-response data set is selected. In this exercise, whenever available, human data of high quality are preferable to animal data. However, if only animal data are available, dose-response data from species that responds most similarly to humans with respect to metabolism, physiology, and pharmacokinetics is preferred. When no clear choice is possible, the most sensitive species is chosen. Secondly, a model to the available data set is applied and extrapolation from the relatively high doses administered to test species in animal bioassay (or the exposures recorded in epidemiologic studies) to the lower environmental exposure levels expected for humans is performed using the model. Although various models have been developed for this purpose (e.g. probit, logit, Weibull), the linearized multistage model has commonly been used by the EPA. After the data are fit to the appropriate model, the upper 95 ^th percent confidence limit of the slope of the resulting dose-response curve is calculated, which is known as the Cancer Slope Factor (CSF). It represents an upper 95 ^th percent confidence limit on the probability of a response per unit intake of a chemical over a lifetime (i.e. dose). Thus, its units are (mg/kg-day) ^-1 . This indicates that there is only a five percent chance that the probability of a response could be greater than the estimated value of CSF. Because the dose-response curve generally is linear only in the low-dose region, the slope factor estimate only holds true for low doses. Toxicity values for carcinogenic effects also can be expressed in terms of risk per unit concentration of the chemical, which are called unit risk factors (URFs). They are calculated by dividing the CSF by adult body weight (70 kg) and multiplying by the adult inhalation rate (20 m ³ /day), for risk associated with unit concentration in air ( EPA, 1989 ).

A number of regulatory agencies responsible for environmental and public health protection have devoted resources in developing and documenting toxicity values for noncarcinogens (RfDs/RfCs) and carcinogens (CSFs/URFs). The following hierarchy of sources is recommended by the EPA in evaluating chemical toxicity for Superfund sites ( EPA, 2003 ):

• Integrated Risk Information System (IRIS) and cited references, which is the prime source for the chemical-specific toxicity value information and can be accessed via: (External Link)
• The Provisional Peer Reviewed Toxicity Values (PPRTV) and cited references developed for the EPA Office of Solid Waste and Emergency Response (OSWER) Office of Superfund Remediation and Technology Innovation (OSRTI) programs (not publicly available).
• Other toxicity values, which includes the following sources of toxicity values that are commonly consulted by the EPA Superfund Program when a relevant toxicity value is not available from either IRIS or the PPRTV database:
  • California Environmental Protection Agency (Cal EPA) Toxicity Criteria Database, available at: (External Link) ;
  • The Agency for Toxic Substances and Disease Registry (ATSDR) Minimal Risk Levels (MRLs, addressing noncancer effects only). MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. These substance-specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors and other responders to identify contaminants and potential health effects that may be of concern at hazardous waste sites. To date, 137 inhalation MRLs, 226 oral MRLs and 8 external radiation MRLs have been derived and can be found at: (External Link) ;
  • The EPA Superfund Health Effects Assessment Summary Tables (HEAST) database and cited references; and
  • Additional sources of toxicity values.