National Toxicology Program

• Review of the Criteria and the Process for Preparing the Biennial Report on Carcinogens (BRC) Now Complete
• Comparison of Former BRC Criteria to Revised Criteria


• Listing/Delisting Procedures


• Formal Review Steps

• NTP Board of Scientific Counselors BRC Subcommittee To Meet November 18-19,1996; Attached Listing of Substances To Be Reviewed
• NTP Board of Scientific Counselors Technical Reports Review Subcommittee To Meet December 11-12, 1996
• NTP Board of Scientific Counselors Meeting December 13, 1996
• Recently Published NTP Long-Term and Toxicity Technical Reports
• The final report of the Workshop on Validation and Regulatory Acceptance of Alternative Toxicological Test Methods Available Upon Request
• Minutes of April 17 NTP Board of Scientific Counselors Meeting and the May 8 Meeting of the Board Subcommittee on the BRC Available Upon Request

REVIEW OF THE CRITERIA AND THE PROCESS FOR PREPARING THE BIENNIAL REPORT ON CARCINOGENS COMPLETED; CHANGES EFFECTIVE IMMEDIATELY

In late 1994 the Director, NTP, initiated a review of the process for preparing the Biennial Report on Carcinogens (BRC). The objectives for revising the process were to:

• broaden the input at all stages throughout the process;
• broaden the scope of scientific review, and
• provide a review of the criteria used for inclusion of substances in the BRC

The review is now complete: DHHS has published new criteria; external peer review is added to the review process through the establishment of a new, standing subcommittee of the NTP Board of Scientific Counselors; and opportunities for public input to the process have been increased. The details of these changes and a description of the new process follow:

Federal Register Notice: September 26, 2996 (Volume 61, Number 188) [Page 50499-50500)

LISTING/DELISTING PROCEDURES

NTP Board Subcommittee Peer Reviews First Group of Substances Nominated for Listing in the BRC Using the Revised Criteria

The next meeting of the new NTP Board of Scientific Counselors' Biennial Report on Carcinogens Subcommittee will be held on November 18-19, 1996, in the Conference Center, Building 101, South Campus, National Institute of Environmental Health Sciences (NIEHS), 111 Alexander Drive, Research Triangle Park, North Carolina. The meeting will begin at 8:30 a.m. and is open to the public. The agenda topic is the peer review of substances nominated for listing in the 8th Biennial Report on Carcinogens.

Tentatively scheduled to be peer reviewed on November 18-19 are 15 substances, listed alphabetically along with supporting information, in the attached table. The order of review is given in the far right column of the table. Copies of a draft summary document which contains the background data and information used to evaluate the nomination of listing may be obtained, as available, from: Dr. C.W.Jamenson, NIEHS, Biennial Report on Carcinogens, MD: WC-05, P.O. Box 12233, Research Triangle Park, NC 27709 (919/541-4096; FAX: 919/541-2242).

Persons wanting to make a formal presentation at the public meeting regarding a particular nominated substance must notify the Executive Secretary, Dr. Larry G. Hart, by telephone, by FAX, or by mail (see contact information below) no later than November 13, 1996. A written copy of comments is requested in advance of the meeting so that copies can be made and distributed to all Subcommittee members and staff and made available at the meeting. Written statements should supplement and may expand on the oral presentation. Oral presentations must be limited to no more than five minutes. In lieu of an oral presentation, written statements may be submitted and should be received by the Executive Secretary by November 13 (see contact information below).

The NTP would welcome receiving carcinogenesis information from completed, ongoing, or planned studies, as well as current production data, human exposure information, and use patterns for any of the substances listed in this announcement. Please contact Dr. C. W. Jameson at the address given above.

Upon request, the Board Executive Secretary, Dr. Larry G. Hart, P.O. Box 12233, Research Triangle Park, North Carolina 27709 (telephone 919/541-3971; FAX 919/541-0295) will furnish the agenda and a roster of Subcommittee members prior to the meeting. Summary minutes subsequent to the meeting will be available upon request.

NTP Board of Scientific Counselors Technical Reports Review Subcommittee to Meet December 11-12, 1996

The Board's Technical Reports Review Subcommittee will meet on December 11-12, 1996. Draft Technical Reports tentatively scheduled for peer review are: 3'-azido-3'-deoxythymidine (AZT)/interferon (IFN); chloroprene; cobalt sulfate; ethylbenzene; isobutyraldehyde; oxazepam;polyvinyl alchohol; primidone; tetrahydrofuran; and theophylline.

The meeting will be held in the Conference Center, Building 101, South Campus, NIEHS. For information please contact Dr. Larry Hart, (919) 541-3971.

NTP Board of Scientific Counselors to Meet December 13, 1996

The NTP Board of Scientific Counselors will meet in public session on December 13, 1996. A preliminary agenda has been developed and primary agenda topics likely will include:

• a detailed discussion and review by the Board of the NTP's nomination and selection process
• presentations by NTP agencies on their ongoing and planned research activities on endocrine disruptors, and
• review by the Board of the NTP's FY97 program plans as contained in the draft Annual Plan.

The meeting will be held in the Conference Center, NIEHS. For information contact Dr. Larry Hart, (919) 541-3971.

Recently Published NTP Long Term Technical Reports

TR 429 Toxicology and Carcinogenesis Studies of Diethylphthalate (CAS No. 84-66-2) in F344/N Rats and B6C3F1 Mice (Dermal Studies) with Dermal Initiation/ Promotion Study of Diethylphthalate and Dimethylphthalate (CAS No. 131-11-3) in Male Swiss (CD-1®) Mice - May 1995.

TR-441 Comparative Initiation/Promotion Skin Paint Studies of B6C3F1 Mice, Swiss (CD-1®) Mice, and SENCAR Mice - February 1996.

TR-447 Toxicology and Carcinogenesis Studies of Acetonitrile (CAS No. 75-05-8) in F344/N Rats and B6C3F1 Mice (Inhalation Studies) - April 1996.

TR-448 Toxicology and Carcinogenesis Studies of Isobutyl Nitrite (CAS No. 542-56-3) in F344 Rats and B6C3F1 Mice (Inhalation Studies) - July 1996.

TR-452 Toxicology and Carcinogenesis Studies of 2,2-Bis(Bromomethyl)-1,3-Propanediol (FR-1138 ®) (CAS No. 3296-90-0) in F344 Rats and B6C3F1 Mice (Feed Studies) - May 1996.

TR-453 Toxicology and Carcinogenesis Studies of Nickel Subsulfide (CAS No. 12035-72-2) in F344 Rats and B6C3F1 Mice (Inhalation Studies) - July 1996.

Recently Published NTP Toxicity Technical Reports

TOX-34 Toxicity Studies of 1-Nitropyrene (CAS No. 5522-43-0) Administered by Inhalation to F344/N Rats - April 1996.

TOX-44 Comparative Toxicity and Carcinogenicity Studies of o-Nitrotoluene and o-Toluidine Hydrochloride (CAS Nos. 88-72-2 and 636-21-5) Administered in Feed to Male F344/N Rats - March 1996.

TOX-45 Renal Toxicity Studies of Selected Halogenated Ethanes Administered by Gavage to F344/N Rats - February 1996.

TOX-50 Toxicity Studies of Cyclohexanone Oxime Administered by Drinking Water to B6C3F1 Mice (CAS No. 100-64-1) - April 1996.

TOX-52 Toxicity Studies of Urethane in Drinking Water and Urethane in 5% Ethanol Administered to F344/N Rats and B6C3F1 Mice (CAS No. 51-79-6) - March 1996.

TOX-54 NTP Summary Report on the Metabolism, Disposition, and Toxicity of 1,4-Butanediol (CAS No. 110-63-4) - May 1996.

The final report of the "Workshop on Validation and Regulatory Acceptance of Alternative Toxicological Test Methods" is now available. The Workshop was held December 11-12, 1995, at the Crystal Gateway Marriott, 1700 Jefferson Davis Highway, Arlington, Virginia.

The purpose of the workshop was to receive comments from the public and invited review panels on the draft report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

Comments and recommendations from the workshop were considered by the ICCVAM in preparing a final report. The ICCVAM report will provide recommended criteria and processes for the validation and regulatory acceptance of new and revised toxicological testing methods. The final ICCVAM report will be available early next year.

ICCVAM was established by the Director, NIEHS and NTP, in response to the NIH Revitalization Act of 1993 (Public Law No. 103-43), which directed NIEHS to: (a) establish criteria for the validation and regulatory acceptance of alternative testing methods; and (b) to recommend a process through which scientifically validated alternative methods can be accepted for regulatory use.

The following Agencies/Institutes are participating in this effort:

Agency for Toxic Substances and Disease Registry
Consumer Product Safety Commission
Department of Agriculture Department of Defense
Department of Energy Department of the Interior
Department of Transportation
Environmental Protection Agency
Food and Drug Administration National Institute for Occupational Safety and Health
National Institutes of Health
National Institute of Environmental Health Sciences
National Cancer Institute
Occupational Safety and Health Administration
National Library of Medicine

To be placed on the mailing list to receive additional information and a copy of the workshop report and/or the current or future revised ICCVAM report, please contact the Central Data Management (CDM), P.O. Box 12233, MD: E1-02, Research Triangle Park, NC 27709; telephone: (919) 541-3419; FAX: (919) 541-3687, or or send e-mail to: NTP Central Data Managementon the Internet.

If you have questions or comments about the ICCVAM, you can contact the co-chairs: Dr. William Stokes, NIEHS, at (919) 541-7997; FAX: (919) 541-0947, or on the Internet at stokes@niehs.nih.gov, or

Dr. Richard Hill, EPA, at (202) 260-2897; FAX: (202) 260-1847, or on the Internet at hill.richard@epamail.epa.gov.

Minutes of the April 17 NTP Board of Scientific Counselors Meeting and the May 8 Meeting of the Board Subcommittee on the BRC Available Upon Request

Minutes from the NTP Board of Scientific Counselors Meeting on April 17, 1996, are available upon request. The Board agenda included presentations and Board comments on research partnerships; new research initiatives on a project studying the effects of endocrine disrupting chemicals on fertility and reproductive tract cancers, and on the program aimed at providing scientific information on the possible health hazards of electric and magnetic fields. The Board was updated on the Biennial Report on Carcinogens criteria review and reviewed and approved concept proposals for continuation of NIEHS/NTP research efforts on the assessment of chemically-induced reproductive and developmental toxicity, and on studies of chemical disposition in mammals.

The NTP Board's Biennial Report on Carcinogens (BRC) Subcommittee held its first meeting at the NIEHS on May 8, 1996. The Subcommittee was established to broaden the scope of scientific review and bring more public input to the preparation of the Biennial Report on Carcinogens (BRC), and will meet once or twice a year, in public session, to review nominations for listing and/or delisting and to receive public comments. The purpose of this first meeting was to provide background on the BRC and the existing review process to foster an open discussion between the NTP and the members that would provide input from the Subcommittee on the process of conducting reviews based on the proposed revised criteria. The meeting concluded with a discussion among the Subcommittee members about the process to be used in their reviews. There was a consensus that there would be a primary and secondary reviewer from the Subcommittee for each chemical and they would evaluate the available information and give their recommendations on the conclusions leading to a vote by the entire Subcommittee.

For copies of the minutes from the April 17th and May 8th meetings, please contact Central Data Management (CDM), P.O.Box 12233, MD: E1-02, Research Triangle Park, NC 27709; telephone (919) 541 3419; FAX: (919) 541-3687, or send e-mail to: NTP Central Data Managementon the Internet.