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External Review Draft on Data-Derived Extrapolation Factors (DDEF)
External Review Draft of the Application of Quantitative Data to Develop Data-Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation
Risk Assessment Forum
Document Links
- Full Draft Document (PDF) (48 pp, 671KB,About PDF)
- Case Studies (PDF) (29 pp, 259KB,About PDF)
- Charge Questions for External Reviewers (PDF) (2 pp, 18KB,About PDF)
Federal Register Notice
- Draft Federal Register Notice (PDF) (5 pp, 739KB,About PDF)
Related Issues
The U.S. Environmental Protection Agency (U.S. EPA) is seeking public comment prior to external peer review of the external review draft of the Application of Quantitative Data to Develop Data-Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation.
Summary
The U.S. EPA is releasing the External Review Draft of "Application of Quantitative Data to Develop Data-Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation." This draft document outlines approaches for developing factors for inter- and intra-species extrapolation based on data describing toxicokinetic and/or toxicodynamic properties of (a) particular agent (s). The document was developed to provide information to the regulated community and other interested parties about deriving and implementing extrapolation factors derived from data instead of defaults and to provide guidance for EPA staff in evaluating such data and/or information. EPA is releasing this document solely for the purpose of seeking public comment prior to external peer review. This document has not been formally disseminated by EPA. This draft guidance does not and should not be construed to represent any EPA policy, viewpoint, or determination.
Background
Key goals of the U.S. EPA included improving the transparency, objectivity, and scientific basis for health-related risk assessment. A significant contribution to achieving these goals is to displace default assumptions with empirically derived information. In 2005, a World Health Organization-sponsored effort produced guidance on the development of Chemical-Specific Adjustment Factors (CSAFs). CSAFs are intended to replace default uncertainty factor values for inter- and intraspecies extrapolation in health risk assessment. This draft DDEF document describes EPA's approach to calculating extrapolation values based on data; these are called data-derived extrapolation factors (DDEF). DDEFs are similar in concept to IPCS/WHO's CSAFs in that the standard extrapolation factors are separated into toxicokinetic (TK) and toxicodynamic (TD) components, and kinetic and mechanistic data are used to derive refined interspecies or intraspecies extrapolation factor(s). Conceptually, DDEFs (and CSAFs) may not be limited to a specific chemical but may also apply to chemicals with common structural characteristics, common mode of action or common toxicokinetic characteristics or determinants. An appendix to this document contains case study examples taken from the Integrated Risk information System (IRIS) and from Program Office records. The case studies present the application of principles contained in this document to data and modeling studies for actual chemicals and should serve as instructional aides.
Public Comment and Peer Review
EPA is releasing this document solely for the purpose of seeking public comment prior to external peer review.
Public comments may be submitted online at http://www.regulations.gov, under Docket ID No. EPA-HQ-ORD-2009-0694. EPA's policy is that all comments received will be included in the public docket without change and may be made available online at www.regulations.gov, including any personal information provided, unless the comment includes information claimed to be Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Do not submit information that you consider to be CBI or otherwise protected by statute through www.regulations.gov or e-mail. The www.regulations.gov website is an "anonymous access" system, which means EPA will not know your identity or contact information unless you provide it in the body of your comment. All comments received by the closing date of the public comment period will be shared with the external peer review panel for their consideration. Comments received after the close of the comment period may be considered by EPA when it finalizes the document.
The document will undergo independent peer review during an expert peer review meeting, which will be convened, organized, and conducted by an EPA contractor in the late fall 2009/ winter 2010 timeframe. The date of the external peer review meeting will be announced in a Federal Register notice.