Guidelines for Carcinogen Risk Assessment (2005)

In 1983, the National Academy of Sciences (NAS)/National Research Council (NRC) published its report entitled Risk Assessment in the Federal Government: Managing the Process. In that report, the NRC recommended that Federal regulatory agencies establish "inference guidelines" to promote consistency and technical quality in risk assessments and to ensure that the risk assessment process was maintained as a scientific effort separate from risk management. EPA responded to this recommendation by publishing a set of risk assessment guidelines in 1986, including Guidelines for Carcinogen Risk Assessment (51 FR 33992, September 24, 1986).

EPA began revising the 1986 cancer guidelines in light of significant advances in our understanding of the processes of carcinogenesis and the modes of actions of disease at the cellular level. Revising the cancer guidelines is in keeping with EPA's original intent when it issued the first set of final risk assessment guidelines in 1986. The risk assessment guidelines were meant to be dynamic, flexible documents that would evolve to reflect the current state of the science and risk assessment practices.

Major issues considered in finalizing revisions to the Cancer Guidelines were:

• beginning with an analysis of available information, and invoking defaults if needed to address uncertainty or the absence of critical information;
• emphasizing key events and processes, starting with the interaction of an agent with a cell, through functional and anatomical changes, that may result in adverse health consequences ("modes of action");
• considering that certain subpopulations, and childhood and other lifestages, may be associated with higher susceptibilities to risk; and
• summarizing the full range of available evidence and describing any conditions associated with conclusions about an agent's hazard potential using a weight-of-evidence narrative and accompanying descriptors.

The Guidelines and Supplemental Guidance serve as EPA's recommendation to Agency risk assessors preparing cancer risk assessments. As EPA prepares cancer assessments under the Integrated Risk Information System (IRIS) program, as well as in other EPA programs, the Agency intends to begin to use the Guidelines and Supplemental Guidance. EPA also intends to consider the Guidelines and Supplemental Guidance along with other selection factors when EPA selects agents for reassessment in annual IRIS agendas (see for example, 70 FR 10616, March 4, 2005).