Guidelines for Carcinogen Risk Assessment (2005)
Risk Assessment Forum
In an effort to update key scientific risk assessment methodologies, EPA has published the revised Guidelines for Carcinogen Risk Assessment 2005 (PDF) (166p, 461K, About PDF). The Guidelines provide a framework to EPA scientists for assessing possible cancer risks from exposures to pollutants or other agents in the environment. They will also inform Agency decision makers and the public about these recommended procedures. Revisions to the Cancer Guidelines are intended to make greater use of the increasing scientific understanding of processes of cancer development. (See also the companion document, Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens).
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.
- 1976 EPA issued the "Interim Procedures and Guidelines for Health Risk Assessments of Suspected Carcinogens."
- 1986 EPA releases the Final Guidelines for Carcinogen Risk Assessment.
- 1996 EPA published the Proposed Guidelines for Carcinogen Risk Assessment (PDF) (143 pp, 650 KB) for public comment. This "proposed" guideline underwent Science Advisory Board (SAB) review in 1997.
- Jan 1999 The SAB reviewed revisions of key sections of the proposed guidelines per previous SAB and public comments.
- Jul 1999 The SAB and Children's Health Protection Advisory Committee (CHPAC) reviewed the Draft Final Revised Guidelines for Carcinogen Risk Assessment for their protection of children.
- Nov 2001 EPA solicited public comment on the finalized Cancer Guidelines and extended the opportunity to provide additional information and comment (66 FR 59593, November 29, 2001). This Notice also identified the July 1999 Draft Revised Guidelines for Carcinogen Risk Assessment as interim guidance pending issuance of final guidelines.
- Mar 2003 EPA released Draft Final Cancer Guidelines to the SAB for comment.
- Mar 2005 EPA published the final Cancer Guidelines.
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).
- Guidelines for Carcinogen Risk Assessment (Final) (PDF) (166 pp, 467KB, about PDF)
- Cancer Guidelines Application Memo (PDF) (2 pp, 114KB, about PDF)
- Cancer Guidelines External Questions and Answers Sheet
- Cancer Guidelines Fact Sheet
- Cancer Guidelines Implementation
- Cancer Guidelines Issuance Fact Sheet
- Summary Response to Public Comments on EPA's Draft Cancer Risk Assessment Guidelines of 1996, 1999, and 2003 (PDF) (21 pp, 88KB, about PDF)
- Presentation on the EPA Cancer Guidelines at the 2005 Toxicology and Risk Assessment Conference
- Presentation on the EPA Cancer Guidelines and Supplemental Guidance (MS PowerPoint)
- Communication I: Application of the Mode of Action Framework in Mutagenicity Determinations for Carcinogenicity (PDF) (8 pp, 651KB, about PDF)
- Communication II: Performing Risk Assessments That Include Carcinogens Described in the Supplemental Guidance as Having a Mutagenic Mode of Action (PDF) (4 pp, 236KB, about PDF)
The final Cancer Guidelines and Supplemental Guidance are available for use by EPA risk assessors, replacing the initial 1986 guidelines publication and the July 1999 interim guidance. Federal Register Notice (posted April 7, 2005).
U.S. EPA. Guidelines for Carcinogen Risk Assessment (2005). U.S. Environmental Protection Agency, Washington, DC, EPA/630/P-03/001F, 2005.