E6-7836. Harmonization in Interspecies Extrapolation: Use of BW3/4

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice of Peer-Review Teleconference with opportunity for public comment.

SUMMARY:

EPA is announcing that Versar, Inc., an EPA contractor for external scientific peer review, plans to convene an independent panel of experts and organize and conduct an external peer review meeting to review the draft document titled, “Harmonization in Interspecies Extrapolation: Use of BW^3/4 as Default Method in Derivation of the Oral RfD” (EPA/630/R-06/001). The peer review meeting is planned to take place by teleconference. On Februrary 15, 2006, EPA announced a 60-day public comment period for the draft document (71 FR 7958). The draft document was prepared by the Agency's Risk Assessment Forum.

The public comment period and the external peer review are separate processes that provide opportunities for all interested parties to comment on the document. In addition to considering public comments submitted in accordance with the February 15, 2006, announcement of a public comment period, EPA intends to forward those comments to Versar, Inc. for the external peer review panel prior to the teleconference.

EPA is releasing this draft document solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. This document has not been formally disseminated by EPA. It does not represent and should not be construed to represent any Agency policy or determination.

The public will be given an opportunity to observe and provide oral comments at this teleconference by registering with Versar, Inc. (see FOR FURTHER INFORMATION CONTACT, below). The draft document and the charge questions for EPA's external peer review are available primarily via the Internet on the Risk Assessment Forum's home page under the External Review Drafts menu at http://cfpub.epa.gov/​ncea/​raf/​index.cfm. In preparing a final report, EPA will consider Versar Inc.'s report of the comments and recommendations from the external peer review meeting and any public comments that EPA receives in accordance with the February 15, 2006, notice (71 FR 7958).

DATES:

The peer review teleconference will be held on June 14, 2006, from 9 a.m. to no later than 5 p.m., with a break for lunch. The teleconference may end earlier than 5 p.m. if less time is needed for the reviewers to complete their discussion. Time will be provided for public observers who wish to make comments on the document.

ADDRESSES:

The draft “Harmonization in Interspecies Extrapolation: Use of BW3/4 as Default Method in Derivation of the Oral RfD” is available primarily via the Internet on the Risk Assessment Forum's home page under the External Review Drafts menu at http://cfpub.epa.gov/​ncea/​raf/​index.cfm. A limited number of paper copies are available from the Technical Information Staff, NCEA-W by telephone: [phone] or by facsimile: 202-565-0050. If you are requesting a paper copy, please provide your name, mailing address, and the document title, “Harmonization in Interspecies Extrapolation: Use of BW^3/4 as Default Method in Derivation of the Oral RfD.” Copies are not available from Versar, Inc.

FOR FURTHER INFORMATION CONTACT:

Members of the public may call into the teleconference as observers, and there will be a limited time for comments from the public. In order to participate, you should contact Mr. Andrew Oravetz of Versar, Inc. at [e-mail] or by phone at 703-642-6832 to register. You will be asked for your name, affiliation, city and state, and contact information. When registering, please also indicate whether you would like to make a statement during the call. Time for public comments is limited, and reservations will be accepted on a first-come, first-served basis. At a time before June 14, 2006, registrants will be given the call-in information for the peer review teleconference.

For technical information, please contact Resha M. Putzrath, Risk Assessment Forum; telephone: [phone]; facsimile: 202-565-0062; or e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

I. Information About the Document

The Agency endorses a hierarchy of approaches to derive human equivalent oral exposures from data from laboratory animals, with the preferred approach being physiologically based toxicokinetic modeling. Intermediate approaches include using some chemical-specific information. In lieu of data to support either of these approaches, body weight scaling to the 3/4 power (BW^3/4) would be endorsed as a general default procedure to extrapolate toxicologically equivalent doses of chronic orally administered agents from laboratory animals to humans for the purposes of deriving an oral Reference Dose (RfD). Use of BW^3/4 in derivation of RfD values would be parallel with current Agency use in derivation of cancer oral slope factors. Thus, this paper would harmonize the two main Agency oral dose-response extrapolation procedures. This generalized default procedure is viewed as an informed, species-specific, dosimetric adjustment factor (DAF) that addresses predominantly toxicokinetic and some toxicodynamic aspects of the interspecies uncertainty factor UF_A. Use of this procedure would result in derivation of a human equivalent exposure, specifically a human equivalent dose (HED) that is to be used in derivation of the oral RfD in a manner parallel to the human equivalent concentration (HEC) in derivation of an inhalation RfC.

Dated: May 15, 2006.

George Alapas,

Deputy Director, National Center for Environmental Assessment.