E6-17137. National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction (CERHR); Availability of the Draft Expert Panel Report on Hydroxyurea and Request for Public Comment on the Draft Report; Announcement of the ...

AGENCY:

National Institute for Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), HHS.

ACTION:

Announcement of a meeting and request for public comment.

SUMMARY:

The CERHR announces the availability of the draft expert panel report for hydroxyurea on November 1, 2006, from the CERHR Web site (http://cerhr.niehs.nih.gov) or in printed text from the CERHR (see FOR FURTHER INFORMATION CONTACT below). The CERHR invites the submission of public comments on sections 1-4 of the draft expert panel report (see SUPPLEMENTARY INFORMATION below). The expert panel will meet on January 24-26, 2007, at the Radisson Hotel Old Town in Alexandria, VA, to review and revise the draft expert panel report and reach conclusions regarding whether exposure to hydroxyurea is a hazard to human development or reproduction. The expert panel will also identify data gaps and research needs. CERHR expert panel meetings are open to the public with time scheduled for oral public comment. Attendance is limited only by the available meeting room space. Following the expert panel meeting and completion of the expert panel report, the CERHR will post the final report on its Web site and solicit public comment on it through a Federal Register notice.

DATES:

The expert panel meeting for hydroxyurea will be held on January 24-26, 2007. Sections 1-4 of the draft expert panel report will be available for public comment on November 1, 2006. Written public comments on the draft report must be received by December 15, 2006. Time is set-aside at the expert panel meeting on January 24, 2007 for oral public comments. Individuals wishing to make oral public comments are asked to contact Dr. Michael D. Shelby, CERHR Director, by January 17, 2007, and if possible, send a copy of the statement or talking points at that time. Persons needing special assistance in order to attend are asked to contact Dr. Shelby at least 7 business days prior to the meeting.

ADDRESSES:

The expert panel meeting on hydroxyurea will be held at the Radisson Hotel Old Town 901 N. Fairfax Street Alexandria, VA 22314-1501 (telephone: [phone], facsimile: 703-683-7597). Comments on the draft expert panel report should be sent to Dr. Michael D. Shelby, CERHR Director, NIEHS, P.O. Box 12233, MD EC-32, Research Triangle Park, NC 27709 (mail), [phone] (fax), or [e-mail] (e-mail). Courier address: CERHR, 79 T.W. Alexander Drive, Building 4401, Room 103, Research Triangle Park, NC 27709.

FOR FURTHER INFORMATION CONTACT:

Dr. Michael D. Shelby, CERHR Director, 919-541-3455, [e-mail].

SUPPLEMENTARY INFORMATION:

Background

Hydroxyurea (CAS RN: 127-07-1) is used in the treatment of cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease used in children aside from blood transfusion. Hydroxyurea may be used in the treatment of children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea may be associated with cytotoxic and myelosuppressive effects and hydroxyurea is mutagenic. Hydroxyurea is FDA-approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell anemia who experience recurrent moderate to severe painful crises. CERHR selected this chemical for evaluation because of (1) increasing use in the treatment of sickle cell disease in children and adults, (2) knowledge that it inhibits DNA synthesis and is cytotoxic, and (3) published evidence of reproductive and developmental toxicity in rodents.

At the expert panel meeting, the expert panel will review and revise the draft expert panel report and reach conclusions regarding whether exposure to hydroxyurea is a hazard to human reproduction or development. Each draft expert panel report has the following sections:

1.0 Chemistry, Use, and Human Exposure.

2.0 General Toxicological and Biological Effects.

3.0 Developmental Toxicity Data.

4.0 Reproductive Toxicity Data.

5.0 Summary, Conclusions, and Critical Data Needs (to be prepared at expert panel meeting).

Request for Comments

The CERHR invites written public comments on sections 1-4 of the draft expert panel report on hydroxyurea. Any comments received will be posted on the CERHR Web site prior to the meeting and distributed to the expert panel and CERHR staff for their consideration in revising the draft report and preparing for the expert panel meeting. Persons submitting written comments are asked to include their name and contact information (affiliation, mailing address, telephone and facsimile numbers, e-mail, and sponsoring organization, if any) and send them to Dr. Shelby (see ADDRESSES above) for receipt by December 15, 2006.

Time is set-aside on January 24, 2007, for the presentation of oral public comments at the expert panel meeting. Seven minutes will be available for each speaker (one speaker per organization). When registering to comment orally, please provide your name, affiliation, mailing address, telephone and facsimile numbers, e-mail and sponsoring organization (if any). If possible, send a copy of the statement or talking points to Dr. Shelby by January 17. This statement will be provided to the expert panel to assist them in identifying issues for discussion and will be noted in the meeting record. Registration for presentation of oral comments will also be available at the meeting on January 24, 2007, from 7:30-8:30 a.m. Persons registering at the meeting are asked to bring 20 copies of their statement or talking points for distribution to the expert panel and for the record.

Preliminary Agenda

The meeting begins each day at 8:30 a.m. On January 24 and 25, it is anticipated that a lunch break will occur from noon-1 p.m. and the meeting will adjourn at 5-6 p.m. The meeting is expected to adjourn by noon on January 26; however, adjournment may occur earlier or later depending upon the time needed by the expert panel to complete its work. Anticipated agenda topics for each day are listed below.

January 24, 2007

• Opening remarks.
• Oral public comments (7 minutes per speaker; one representative per group).
• Review of sections 1-4 of the draft expert panel report on hydroxyurea.
• Discussion of Section 5.0 Summary, Conclusions, and Critical Data Needs.

January 25, 2007

• Discussion of Section 5.0 Summary, Conclusions, and Critical Data Needs.
• Preparation of draft summaries and conclusion statements.

January 26, 2007

• Presentation, discussion of, and agreement on summaries, conclusions, and data needs.
• Closing comments.

Expert Panel Roster

The CERHR expert panel is composed of independent scientists selected for their scientific expertise in reproductive and/or developmental toxicology and other areas of science relevant for these evaluations.

Erica Liebelt, M.D. (Chair), University of Alabama, Birmingham, AL.

Sophie Balk, M.D., Albert Einstein College of Medicine, New York, NY.

Will Faber, PhD, Consultant, Victor, NY.

Jeffrey Fisher, PhD, University of Georgia, Athens, GA.

Claude Hughes, Jr., M.D., PhD, Quintiles, Inc., Research Triangle Park, NC.

Sophie Lanzkron, M.D., Johns Hopkins University, Baltimore, MD.

Kerry Lewis, M.D., Howard University, Washington, DC.

Harihara Mehendale, PhD, University of Louisiana, Monroe, LA.

Marvin Meistrich, PhD, University of Texas, Houston, TX.

John Rogers, PhD, U.S. Environmental Protection Agency, Research Triangle Park, NC.

Aziza Shad, M.D., Georgetown University, Washington, DC.

Richard Skalko, PhD, East Tennessee State University, Johnson City, TN.

Edward Stanek III, PhD, University of Massachusetts, Amherst, MA.

Background Information on the CERHR

The NTP established the NTP CERHR in June 1998 [Federal Register, December 14, 1998 (Volume 63, Number 239, page 68782)]. The CERHR is a publicly accessible resource for information about adverse reproductive and/or developmental health effects associated with exposure to environmental and/or occupational exposures. Expert panels conduct scientific evaluations of agents selected by the CERHR in public forums.

The CERHR invites the nomination of agents for review or scientists for its expert registry. Information about CERHR and the nomination process can be obtained from its homepage (http://cerhr.niehs.nih.gov) or by contacting Dr. Shelby (see FOR FURTHER INFORMATION CONTACT above). The CERHR selects chemicals for evaluation based upon several factors including production volume, potential for human exposure from use and occurrence in the environment, extent of public concern, and extent of data from reproductive and developmental toxicity studies.

CERHR follows a formal, multi-step process for review and evaluation of selected chemicals. The formal evaluation process was published in the Federal Register on July 16, 2001 (Volume 66, Number 136, pages 37047-37048) and is available on the CERHR Web site under “About CERHR” or in printed copy from the CERHR.

Dated: October 5, 2006.

Samuel H. Wilson,

Deputy Director, National Institute of Environmental Health Sciences and National Toxicology Program.