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External Review Draft of Data-Derived Extrapolation Factors (DDEF)
Risk Assessment Forum
External Review Draft of the Guidance for Applying Quantitative Data to Develop Data-Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation
Summary
The U.S. Environmental Protection Agency (U.S. EPA) is seeking public comment prior to external peer review of the draft document Guidance for Applying Quantitative Data to Develop Data-Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation. The comment period will run for 45-days from June 9, 2011 to July 24, 2011.
The uncertainty in extrapolating the results from animal toxicity studies to humans is divided into animal to human (interspecies) differences and human variability (intraspecies differences). This draft document outlines approaches for using data for particular agents to develop factors to compensate for those uncertainties. The document was developed to provide guidance for EPA staff in evaluating such data and/or information, and to inform the regulated community and other interested parties about deriving and implementing extrapolation factors derived from data in lieu of default values. 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 This draft guidance does not and should not be construed to constitute EPA policy, viewpoint, or determination.
Background
Data Derived Extrapolation Factors (DDEF) methodology is derivative of a World Health Organization (WHO) initiative. In 2005, the WHO produced guidance on the development of Chemical-Specific Adjustment Factors (CSAFs). CSAFs were developed to replace default assessment factors to address uncertainties in inter- and intraspecies extrapolation in human health risk assessments. This draft DDEF document was developed to better align the WHO approach with EPA's policies and practices to conducting human health assessments on chemicals. EPA’s DDEF methods are similar in concept to 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). An appendix to the DDEF 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 2011. The date of the external peer review meeting will be announced in a future Federal Register notice.
DDEF External Review Draft (PDF) (58 pp, 1Mb, About PDF)
DDEF External Review Case Study (PDF) (30 pp, 946K, About PDF)