Meetings: dose issues; peer review,

[Federal Register: September 27, 2000 (Volume 65, Number 188)]

[Notices]

[Page 58097-58099]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr27se00-106]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

National Institute of Environmental Health Sciences, NIH; National Toxicology Program; Peer Review Meeting on Low-Dose Issues for Endocrine Disruptors; Update on Meeting Scope; Meeting Agenda; and Registration Information

Summary

The National Toxicology Program (NTP) is organizing a Peer Review to evaluate dose-response relationships for endocrine disrupting chemicals. In particular, the panel will evaluate whether chemicals can cause hormone-related effects at doses lower than those typically used in the standard toxicological dose-setting paradigm. The U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program will use the results from this peer review to assist in determining how to identify and characterize potential low-dose effects that may arise during endocrine disruptor screening, testing, and hazard assessment. If the

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review panel concludes that the current data on low-dose effects are inconclusive, it will be asked to describe specific research that would resolve the ambiguities. The Peer Review will take place October 10-12, 2000 at the Sheraton Imperial Hotel and Convention Center, Research Triangle Park, NC. This meeting is open to the public.

On January 6, 2000 the NTP published a Federal Register notice

[Volume 65, Number 4, pages 784-787] outlining plans for the Peer Review meeting and soliciting public input into the process. A second Federal Register notice was published April 17, 2000 (Volume 65, Number 74, pages 20478-20479] that broadened the scope of the research studies and data to be considered for inclusion in this peer review. This notice supplements the earlier ones and provides an agenda, registration information, and updated details about the Peer Review.

Endocrine Disruptor Peer Review

1. Background and Scope

   The goals of this peer review are to review the scientific evidence related to the low-dose effects of endocrine disruptors and to consider their implications for the development, validation, and interpretation of test protocols for reproductive and developmental toxicity. The intent is to examine data from major selected studies (excluding studies on dioxin and dioxin-like compounds) supporting the presence or absence of low-dose effects and to evaluate the likelihood and significance of these and/or other potential low-dose effects for humans. A main topic to be addressed is defining the shape of the dose- response curves for endocrine-active substances in the low-dose region. The analysis and evaluation will be accomplished during this three-day scientific peer review that includes plenary sessions and several subpanel meetings. This peer review is open to the public.

   The EPA has established an official record for this action under docket control number OPPTS-42208A. The official record consists of the selected and background studies being considered in this peer review, any public comments received, and other information related to this action. The public version of the official record is available for inspection in the TSCA Nonconfidential Information Center, North East Mall Room B-607, Waterside Mall, 401 M. Street, SW, Washington, DC. The Center is open from noon to 4 PM., Monday through Friday, excluding legal holidays. The telephone number of the Center is (202) 260-7099.

2. Tentative Agenda

   Tuesday, October 10, 2000 8:30-8:45 am

   Scope of Review 8:45-9:00am

   Charge to Panel 9:00-10:15 am

   Body of Knowledge Presentation and Discussion--Dr. Frederick S. vom Saal, University of Missouri 10:15-10:45 am

   Break 10:45 am-Noon

   Body of Knowledge Presentation and Discussion--Dr. John Ashby, Zeneca, Central Toxicology Laboratory, United Kingdom Noon-1:00pm Lunch 1:00-2:15 pm

   Body of Knowledge Presentation and Discussion--Dr. K. Barry Delclos, National Center for Toxicological Research 2:15-3:30 pm

   Body of Knowledge Presentation and Discussion--Dr. John C. O'Connor, DuPont Haskell Laboratory 3:30-3:45 pm

   Break 3:45-4:30 pm

   Summary of Other Bodies of Knowledge Studies 4:30-5:00pm

   Report from the Statistics and Dose-Response Modeling

   Subpanel--Statistical Evaluations 5:00-5:20 pm

   Report from the Statistics and Dose-Response Modeling

   Subpanel--Mechanism-Based Dose-Response Modeling 5:20-6:15 pm

   Dinner 6:15-8:00pm

   Public Comments 8:00-9:00pm

   Subpanels: Initial Meeting Wednesday, October 11, 2000 8:30-5:00pm

   Subpanel Meetings

   Bisphenol A

   Other Environmental Estrogens and Estradiol

   Androgens and Anti-Androgens

   Biological Factors (i.e. confounders: diet, strain, etc.) and Study Design 10:00-10:30 am

   Break Noon-1:00pm

   Lunch 2:30-3:00pm

   Break Thursday, October 12, 2000 8:30-10:00am

   Subpanel Meetings 10:00-10:30 am

   Break 10:30 am-Noon

   Presentation and Discussion of Subpanel Reports Noon-1:00pm

   Lunch 1:00-2:30 pm

   Presentation and Discussion of Subpanel Reports 2:30-3:00pm

   Break 3:00-5:00pm

   Presentation and Discussion of Subpanel Reports

3. Peer Review Evaluation and Analysis

   The NTP is establishing a scientific panel with broad expertise including endocrinology, reproductive and development biology/ toxicology, statistics, modeling, receptor biology, and molecular biology to conduct the evaluation and analysis for this peer review. The Panel will be divided into five subpanels: (1) Bisphenol A, (2) Other Environmental Estrogens and Estradiol, (3) Androgens and Anti- Androgens, (4) Biological Factors (i.e. confounders: diet, strain, etc.) and Study Design, and (5) Statistics and Dose-Response Modeling. At the peer review, members of the Statistics and Dose-Response Modeling Subpanel will be available to interact with the other subpanels. A list of the Panel members and their subpanel assignments is available on-line through the NTP web site (http://ntp- server.niehs.nih.gov, What's New), from the EPA docket (see above), or by contacting the NTP Liaison and Scientific Review Office (contact information given below).

   Studies for inclusion in this peer review are catalogued as either Selected Studies or Background Information. A list of the studies included in each group is found on the NTP web site (see above), from the EPA docket (see above), or by contacting the NTP Liaison and Scientific Review Office (see below). Copies of most studies are available from the EPA docket. As more information is received, the lists will be updated and studies will be added to the docket. Raw data for the Selected Studies will be available from the EPA docket no earlier than October 3rd. Individuals wanting to obtain a copy of particular datasets should bring two rewritable CDs to the EPA docket so the data can be transferred. The datasets will be available in ASCII format as well as SAS transport files.

   The Panel will have available to them copies of both the Selected Studies and Background Information. Prior to the peer review, the Statistics and Dose-

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   Response Modeling Subpanel will reevaluate selective laboratory data and analyze dose-response relationships from identified studies and make that information available to the other subpanels for inclusion in their evaluations. Analyses by the Panel will focus on the interpretation of the Selected Studies showing or refuting effects at low doses for endocrine disruptors on reproductive and developmental endpoints. In addition, at the meeting invited researchers will make oral presentations to the Panel during the plenary sessions (see tentative agenda) and will be available for in-depth discussions during subpanel meetings. The individual subpanels will review all evidence, including relevant pharmacokinetic and mechanistic information that may have a bearing on the low-dose issue. In addition, they will consider the consistency in the data (within and across studies), the strength and specificity of the evidence for low-dose effects, the evidence for defining the shape of the dose-response curves in the low-dose regions, and the biologic plausibility of the reported effect(s). The subpanels will identify research gaps and as possible, suggest ways to address those gaps.

   All subpanels will prepare reports of their conclusions, including areas of consensus and disagreement and identify research needs that would help resolve ambiguities. Following the meeting, the NTP will receive the final reports from the individual subpanels and will synthesize this information into its own report. The NTP will solicit public comments on the NTP report, synthesize those comments, and incorporate them into its final transmission to the EPA and other Federal agencies. The NTP will also publish the report in a scientific journal. This report will be posted on the NTP web site (see above) and made available to the panel members and the public; requests for hardcopies can be made to the NTP Liaison and Scientific Review Office (see below).

4. Public Comments

   The Public is invited to attend the Peer Review with the number of observers limited only by the space available. A formal public comment period is scheduled for October 10 (see tentative agenda) for interested persons or groups to present their views and comments to the Panel (please limit speakers to one per group). The Public is invited to present oral comments at the meeting or to submit written comments by October 6, 2000 for distribution to the Panel at the meeting. Oral presentations will be limited to five to seven minutes per speaker depending upon the number of speakers. Individuals presenting oral comments are asked to provide 40 copies of their statement at registration for distribution to the Panel. For planning purposes, persons wishing to give oral comments are asked to check the box provided on the Registration Form (information provided below) or contact the NTP Liaison and Scientific Review Office (see below), although requests for oral presentations will also be accepted on-site (subject to availability of time). Persons registering for oral comments or submitting written remarks are asked to include their contact information (name, address, affiliation, telephone, fax, and e- mail). Written comments should be sent to the NTP Liaison and Scientific Review Office.

   In addition to the plenary sessions, the Public is invited to attend the individual subpanel meetings. When registering, the Public is asked to indicate their first and second subpanel choices on the registration form. Attendance in these meetings will be limited by the available space and the NTP will make every effort to honor specific requests.

5. Meeting Registration

   The Peer Review is open to the public, limited only by the space available. The registration fee is $90 per registrant. In order to plan appropriately, advance registration is requested by September 29, 2000, although on-site registration will be available (subject to space availability). Registration Forms can be obtained through the Internet at the NTP web site (http://ntp-server.niehs.nih.gov, What's New?) or by contacting the NTP Liaison and Scientific Review Office, NIEHS, P.O. 12233, MD A3-01, Research Triangle Park, NC, telephone: 919-541-0530; fax: 919-541-0295; and e-mail: liaison@starbase.niehs.nih.gov.

   Dated: September 13, 2000. Kenneth Olden, Director, NIEHS/NTP.

   [FR Doc. 00-24731Filed9-26-00; 8:45 am]

   BILLING CODE 4140-01-P