E7-19119. Notice of Availability of the External Review Draft of a “Framework for Determining a Mutagenic Mode of Action for Carcinogenicity: Using EPA's 2005 Cancer Guidelines and Supplemental Guidance for Assessing Susceptibility From Early-Life ...

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice of Document Availability for Public Comment.

SUMMARY:

The Environmental Protection Agency (EPA) is announcing a 60-day public comment period for the External Review Draft of the “Framework for Determining a Mutagenic Mode of Action for Carcinogenicity: Using EPA's 2005 Cancer Guidelines and Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens” (or Framework). EPA is releasing this draft document solely for the purpose of seeking public comment prior to external peer review. Following the period for public comment, the document will be reviewed by an external panel of experts. The date and other details about the external review will be published in a separate Federal Register notice. EPA will consider both the public and the external peer review comments when revising the draft Framework. Members of the public may obtain the draft guidance from http://www.regulations.gov;​; or http://www.epa.gov/​osa/​mmoaframework;​; or from Dr. Resha Putzrath via the contact information below.

The purpose of the Framework is to expand and clarify discussions found in the Cancer Guidelines and Supplemental Guidance on characteristics to be evaluated for a chemical's potential for a mutagenic mode of action (MOA). These documents can be obtained from http://www.epa.gov/​cancerguidelines. This Framework document is not a prescriptive guide on how any particular type of assessment should be conducted within an EPA program or regional office. Rather, it is a science-based document that is intended to help EPA's risk assessors determine whether data support a finding of a mutagenic MOA for carcinogenicity. It discusses mutagenicity only within the context of a mutagenic MOA for carcinogenicity and not for other adverse endpoints that involve mutations. EPA's Risk Assessment Forum oversaw the development of this draft document.

EPA's Cancer Guidelines emphasize using MOA information in interpreting and quantifying the potential cancer risk to humans. The Supplemental Guidance discusses the use of age-dependent adjustment factors (ADAFs) with the derived cancer slope factors (and appropriate age-specific estimates of exposure) in the development of risk estimates if the weight of evidence supports a mutagenic MOA. This default approach is used only when appropriate chemical-specific data are not available on susceptibility from early-life exposures.

ADDRESSES:

The draft document is available electronically through the EPA Office of the Science Advisor's Web site at: http://www.epa.gov/​osa/​mmoaframework.

FOR FURTHER INFORMATION CONTACT:

For more information, contact Dr. Resha Putzrath, Office of the Science Advisor, Mail Code 8105-R, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW., Washington, DC 20460; telephone number: [phone]; fax number: [phone], e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

In response to requests from numerous stakeholders following EPA's release of the Supplemental Guidance in 2005, the Risk Assessment Forum has prepared a framework document that expands and clarifies characteristics used to determine a chemical's potential for a mutagenic MOA for carcinogenicity. This determination affects consideration of adjusting cancer potencies via the ADAFs when exposures of these carcinogens occur to children. The Framework is meant to complement EPA's 2005 Cancer Guidelines and Supplemental Guidance. In order to use the Framework properly, the chemical of interest must already have a weight-of-evidence determination for carcinogenicity. The Framework does not provide an approach to hazard identification. Rather, it gives information useful to determining whether MOAs by which the chemical causes cancer include mutagenicity as an early key event; “key event” is a term of art described in the mode-of-action framework in the Cancer Guidelines.

Dated: September 21, 2007.

George M. Gray,

EPA Science Advisor.