Document ID: EPA-HQ-OA-2007-0976-0002
Agency: epa
Document Type: Notice
Title: Notice of Availability of the External Review Draft of a "Framework for Determining a Mutagenic Mode of Action for Carcinogenicity: Using EPAs 2005 Cancer Guidelines and Supplemental Guidance for Assessing Susceptibility From Early-Life Exposure to Carcinogens"
Posted Date: 2007-09-27T04:00Z

[Federal Register: September 27, 2007 (Volume 72, Number 187)]
[Notices]
[Page 54910-54911]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr27se07-51]

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ENVIRONMENTAL PROTECTION AGENCY

[FRL-8474-3]

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 Exposure to
Carcinogens''

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice of Document Availability for Public Comment.

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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public may obtain the draft guidance from http://www.regulations.gov; or http://www.epa.gov/osa/mmoaframework; or from Dr.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
ath 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: (202) 564-3229; fax number:
(202) 564-2070, e-mail: putzrath.resha@epa.gov.

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

[[Page 54911]]

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.
 [FR Doc. E7-19119 Filed 9-26-07; 8:45 am]

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