Draft Benchmark Dose Technical Guidance Document

AGENCY:

Environmental Protection Agency.

ACTION:

Notice of Peer-Review Workshop and Public Comment Period.

SUMMARY:

The U.S. Environmental Protection Agency (EPA) is announcing that Eastern Research Group, Inc. (ERG), an EPA contractor for external scientific peer review, will organize, convene, and conduct an external peer-review workshop to review the draft document titled: “Benchmark Dose Technical Guidance Document” (EPA/630/R-00/001). The EPA is also announcing a 30-day public comment period for the draft document. The document was prepared by an EPA Risk Assessment Forum Technical Panel. The Technical Panel will consider the peer-review and public comment submissions in finalizing the document.

DATES:

The peer-review workshop will begin on Thursday, December 7, 2000, at 8:30 a.m. and end at 5:00 p.m., then reconvene Friday, December 8, 2000, from 8:00 a.m. to 1:00 p.m. Members of the public may attend as observers, and there will be a limited time for comments from the public. The 30-day public comment period begins November 20, 2000, and ends December 20, 2000.

ADDRESSES:

The external peer-review workshop will be held at the Holiday Inn Capital, 550 C Street SW, Washington DC 20024. To attend the workshop register by November 30, 2000 by calling ERG at (781) 674-7374 or send a facsimile to (781) 674-2906. You may also register on the Internet at http://www.erg.com/conferences/index.htm , or by E-mail at confmail@erg.com. Space is limited, and reservations will be accepted on a first-come, first-served basis. There will be a limited time for comments from the public during the workshop. Please let ERG know if you wish to make comments.

The draft “Benchmark Dose Technical Guidance Document” is available primarily via the Internet at http://www.epa.gov/ncea/bnchmrk/bmdspeer.htm. A limited number of paper copies are available from the Technical Information Staff (8623D), NCEA-W; telephone: 202-564-3261; facsimile: 202-565-0050. If you are requesting a paper copy, please provide your name, mailing address, and the document title, draft “Benchmark Dose Technical Guidance Document.” Copies are not available from ERG. Comments may be mailed to the Technical Information Staff (8623D), NCEA-W, U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Washington, DC 20460, or delivered to the Technical Information Staff at 808 17th Street, NW, 5th Floor, Washington, DC 20006; telephone: 202-564-3261; facsimile: 202-565-0050. Comments should be in writing and must be postmarked by December 20, 2000. Please submit one unbound original with pages numbered consecutively, and three copies of the comments. For attachments, provide an index, number pages consecutively with the comments, and submit an unbound original and three copies. Electronic comments may be emailed to: nceadc.comment@epa.gov.

Please note that all technical comments received in response to this notice will be placed in a public record. For that reason, commentors should not submit personal information (such as medical data or home address), Confidential Business Information, or information protected by copyright. Due to limited resources, acknowledgments will not be sent.

FOR FURTHER INFORMATION CONTACT:

For workshop information, registration, and logistics, contact ERG, 110 Hartwell Avenue, Lexington, Massachusetts 02173; telephone: (781) 674-7374; facsimile: (781) 674-2906.

For information on the public comment period, contact Marilyn Brower, Risk Assessment Forum Staff; telephone: 202-564-3363; facsimile: 202-565-0062; or email: brower.marilyn@epa.gov.

SUPPLEMENTARY INFORMATION:

The U.S. EPA conducts risk assessments for an array of health effects that may result from exposure to environmental agents and that require an analysis of the relationship between exposure and health-related outcomes. The dose-response assessment can be approached as a two-step process, the first being the definition of a point of departure (POD) and the second extrapolation from the POD to low environmentally-relevant exposure levels. The benchmark dose (BMD) approach provides a more quantitative alternative to the first step in the dose-response assessment than the current no-observed-adverse-effect-level/lowest-observed-adverse-effect-level (NOAEL/LOAEL) process for noncancer health effects and can be applied to determining the POD proposed for cancer endpoints (EPA, 1996). As the Agency moves toward harmonization of approaches for cancer and noncancer risk assessment, the dichotomy between cancer and noncancer health effects is being replaced by consideration of mode of action and whether the effects of concern are likely to be linear or nonlinear at low doses. Thus, the purpose of this document is to provide guidance for the Agency on the application of the BMD approach in determining the POD, whether a linear or nonlinear low dose extrapolation is used.

The document addresses a number of issues that must be resolved in order to apply the BMD approach for dose-response assessment in a consistent manner. These issues include: (1) Determination of appropriate studies and endpoints on which to base BMD calculations; (2) selection of the benchmark response (BMR) value; (3) choice of the model to use in computing the BMD; (4) details surrounding computation of the confidence limit for the BMD (BMDL); and (5) reporting requirements for BMD and BMDL computation.

Since the methods for BMD computation require appropriate software, another purpose of this document is to provide enough information about preferred computational algorithms to allow users to make an informed choice in the selection of that software. The document does not advocate use of any particular software package, although it is recommended that software with well documented algorithms, such as the Agency's BMD software (BMDS) package, be used. Nor is this guidance intended to document any particular software package, although it will present examples for illustrative purposes that use the Agency's BMDS package. It is also expected that this guidance will inform the design of studies for the computation of BMDs and dose-response analysis, though this will not be covered explicitly. The terminology used in the document is consistent with the EPA's BMDS. This software is available on the Internet at http://www.epa.gov/ncea/bmds.htm.

The Risk Assessment Forum has been active in promoting research and discussion on BMD issues since 1990. In 1993 the Risk Assessment Forum sponsored a colloquium on the applications of BMD methods to noncancer risk assessment. The focus of this colloquium was to review a Forum draft report that outlined the techniques and presented the major questions and decisions involved in applying the BMD method. Following this a technical panel published a background document on the use of BMD in health risk assessment (EPA/630/R-94/007). In the ensuing years the Forum sponsored several workshops and symposia on the BMD approach, including a 1996 external peer review on an earlier draft of the document presently undergoing review. Following this external peer review, the Technical Panel will consider reviewers' and public comments in finalizing the document.

This document is intended to be updated as new information becomes available that would suggest approaches and default options alternative or additional to those indicated here and should not be viewed as precluding additional research on modified or alternative approaches that will improve quantitative risk assessment.