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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 Exposure to Carcinogens” Notice 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 Members of the public may obtain the draft guidance from http://www.regulations.gov; or http://www.epa.gov/osa/mmoaframework; or from Dr.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. 2007-09-27 2007 9 https://www.federalregister.gov/documents/2007/09/27/E7-19119/notice-of-availability-of-the-external-review-draft-of-a-framework-for-determining-a-mutagenic-mode https://www.govinfo.gov/content/pkg/FR-2007-09-27/pdf/E7-19119.pdf Environmental Protection Agency 145 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...

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