US-EPA General Approach

In 1996, the US-EPA published their Proposed Guidelines for Carcinogen Risk Assessment (US-EPA 1996). These Proposed Guidelines were a revision of the 1986 Guidelines for Carcinogen Risk Assessment (US-EPA 1986) and introduced, among others, a new approach for the quantitative risk assessment. A revised draft Guidelines was launched in 1999 (US-EPA 1999) and the final version was published in 2005 (US-EPA 2005). 

The major change from the previous guidelines in terms of the quantitative risk assessment is that the LMS model no longer is the recommended default approach for low-dose extrapolation. Instead, an MOE approach is recommended based on curve fitting within the range of observation with extrapolation from a UED (the 95% lower confidence limit on a dose associated with an extra tumor risk) chosen to be representative of the lower end of the observed range. 

The following overview of the US-EPA revised quantitative approach for cancer risk assessment is based on the final version of the Guidelines for Carcinogen Risk Assessment (US-EPA 2005). 

In the absence of sufficient data to develop a robust, biologically based model for quantitative risk assessment, a single curve-fitting model for each type of data set is preferred. It is noted that many different curve-fitting models have been developed, and those that fit the observed data reasonably well may lead to several-fold differences in estimated risk at the lower end of the observed range. Therefore, the US-EPA uses a standard curve-fitting procedure for tumor incidence data. 

The use of information on the mode of action in the assessment of potential carcinogens is a main focus of the revised cancer guidelines because of the significant scientific advances that have developed concerning the causes of cancer induction. 

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