National Toxicology Program

           Petitions for listing or delisting an agent, substance, or mixture in the Biennial Report on Carcinogens (BRC) should be submitted to the National Toxicology Program (NTP)¹. Petitions must contain a rationale for listing or delisting as either a "known human carcinogen" or a "reasonably anticipated human carcinogen." Appropriate background information and relevant data (e.g. Journal articles, NTP Technical Reports, IARC listings, exposure surveys, release inventories, etc.) which support a petition should be provided or referenced when possible.

           An agent, substances, or mixture petitioned for listing or delisting will be announced in the Federal Register, trade journals, and NTP publicatins to solicit public comment. The original petition and all comments received will be evaluated by a National Institute of Environmental Health Sciences (NIEHS/NTP) Review Group (RG1), composed of scientists from the NIEHS/NTP, to determine if the information provided is sufficient to merit further consideration. If it is determined the petition warrants formal consideration, the NTP may initiate an independent search of the literature and prepare a draft review document for the substance under consideration. NTP draft documents will be prepared according to the following general format:

1. Introduction
   1. Chemical Information
      • synonyms, trade names, CAS #s, molecular formula, molecular structure, etc.
   2. Physical-Chemical Properties
   3. Identification of Structural Analogs
2. Exposure Assessment
   1. Production
   2. Use
   3. Environmental Exposure
      • environmental occurrence, environmental release, drinking water and food content, consumer products, occupational exposures, biomarkers of exposure
   4. Regulations
      • Occupational Exposure Limits (standards and criteria), 'other' standards and criteria
3. Human Studies
   1. Epidemiology Studies
      • occupational studies, clinical trials, consumer exposure, other "non-occupational" exposures
   2. Laboratory Studies
      • controlled exposures
   3. Poisonings
      • case reports, accidents, symptoms, and clinical signs
4. Animal Carcinogenicity Studies
   • subdivided by species
5. Genotoxicity
6. Mechanistic and Other Relevant Studies

           Data used in the preparation of Sections 3 through 6 of the draft document must come from publicly available, peer reviewed sources.

           If it is determined that the petition contains insufficient information to warrant consideration by the NTP, it may be returned to the original petitioner who may be invited to resubmit the petition with additional justification, which may include new data, exposure information, etc. A notice, stating the action taken for a petitioned substance found to contain insufficient justification for consideration, will be published in the Federal Register, trade journals, and NTP news updates, and included in subsequent editions of the BRC with the reason(s) why it was not considered further. This decision will also be forwarded to the NTP Executive Committee and the NTP Board of Scientific Counselors.

           The following describes the review process for petitions that are considered by the NTP for listing in or delisting from the Biennial Report on Carcinogens.

NIEHS/NTP Review Group (RG1)

           The original petition and all public comments received in response to a petition will be reviewed by RG1. Assignment of a primary and secondary reviewer will be made upon receipt of a petition. Reviewers will lead discussions concerning the adequacy of the petition. If the petition warrants formal consideration, a search of pertinent data bases will be performed and available citations will be reviewed by the primary reviewer. The primary reviewer will identify the relevant articles, and after consultation with the secondary reviewer, will obtain the identified literature. A draft summary of all available information from the original petition and the literature search will be prepared. The primary and secondary reviewers will examine the petition, the literature citations, and the draft document for completeness and adequacy. The draft document will be revised if necessary and presented by the primary reviewer to the RG1. Public comments received in response to announcements of petitions will also be considered. The RG1 will make a recommendation for those petitions determined to contain sufficient information for listing or delisting in the BRC. The petition then continues through the review process.

           Petitions reviewed by RG1 for which sufficient information could not be obtained will not proceed further. The subsequent BRC review groups, as well as the NTP Executive Committee, will be informed of this action and will have access to the information on why it will not proceed further. The original petitioner will be notified of the RG1 action and will be invited to resubmit the petition with additional justification. All petitioned agents, substances, or mixtures reviewed by RG1 but not selected for listing or delisting will be included in the subsequent edition of the BRC with the reason(s) why they were not considered further.

NTP Executive Committee's Working Group (RG2)

           The second review of petitions is by the NTP Executive Committee's Working Group (RG2). RG2 is a Governmental interagency group that assesses whether relevant information of the petitioned agent, substance, or mixture is available and sufficient for listing in or delisting from the BRC. A reviewer for each petition will be assigned from the RG2 and will be responsible for reviewing the draft document and for leading the Working Group's discussion of the petition. Public comments received in response to announcements of petitions will also be considered by RG2 during the review. Upon completion of its review, RG2 will provide comments and recommendations for any changes and/or additions to the draft document and also make its recommendations for listing or delisting.

Board of Scientific Counselors BRC Subcommittee

           External peer review for petitions will be performed by a subcommittee of the NTP Board of Scientific Counselors. The subcommittee will review petitions in a public meeting. Prior to public review, a notice will be published in the Federal Register, trade journals, and NTP Liaison Office updates, soliciting public comment. The notice will also invite interested groups or individuals to submit written comments and/or to address the subcommittee during the review meeting. Reviewers for each petition will be assigned from the subcommittee and will be responsible for reviewing the draft document and leading the subcommittee's discussion of the petition. Upon completion of its review, the subcommittee will provide: comments and recommendations for any changes and/or additions to the draft document; and recommendations for listing or delisting the petitioned agent, substance, or mixture.

Public Comment

           Upon completion of the reviews by RG1, RG2, and the Board subcommittee, those petitioned agents, substances, or mixtures which are recommended for listing in or delisting from the BRC, will be published in the Federal Register, trade journals, and NTP publications; and public comment and input on the recommendations will be solicited.

NTP Executive Committee

           The recommendations of RG1, RG2, the Board subcommittee, and all public comments will be presented to the NTP Executive Committee² for review and comment.

NTP Director

           The Director, NTP, reviews all recommendations and makes final decisions regarding the proposed listing and/or delisting and submits the BRC to the Office of the Secretary, DHHS. Upon review and approval by the Secretary, DHHS, a notice of the BRC publication, indicating all newly listed or delisted agents, substances, or mixtures, will be published in the Federal Register, trade journals, and NTP publications.

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¹National Toxicology Program, Biennial Report on Carcinogens MD WC-05, PO Box 12233, Research Triangle Park, NC 27709. For informaiton contact: Dr. C.W. Jameson, phone: 919-541-4096, Fax: 919-541-2243, E-mail: jameson@niehs.nih.gov

²Agencies represented on the NTP Executive Committee include: Agency for Toxic Substances and Disease Registry (ATSDR), Consumer Produce Safety Commission (CPSC), Environmental Protection Agency (EPA), Food and Drug Administration (FDA), National Institute for Occupational Safety and Health (NIOSH), Occupational Safety and Health Administration (OSHA), Department of Health and Human Services (DHHS), National Institutes of Health (NIH), National Cancer Institute (NCI), and National Institute of Environmental Health Sciences/NTP (NIEHS/NTP).