National Toxicology Program

[Federal Register: July 14, 1999 (Volume 64, Number 134)]
[Notices]
[Page 37992-37995]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

National Toxicology Program Public Meeting to receive comment on the review procedures and listing criteria used in the preparation of the DHHS Report on Carcinogens (RoC); September 15, 1999, Ronald Reagan Building, The International Trade Center, 1300 Pennsylvania Avenue, NW, Washington, DC, beginning at 9 am.

The National Toxicology Program announces a public meeting for the purpose of receiving comment on the procedure for reviewing nominations for listing in or delisting from the RoC and the current listing criteria used for evaluation of the nominations to the RoC. The purpose of this public meeting is to obtain input and to provide all interested parties an opportunity to express their views about the review process and/or the evaluation criteria and to comment on the views expressed by others.

The meeting will begin at 9 am and will conclude at 5 p.m. or at the conclusion of the public comment and discussion, if sooner. On-site registration will begin at 8:30 am. Details regarding registration follow. Attendance at the meeting is limited only by the space available.

Background: The DHHS Report on Carcinogens (RoC) is a public information document prepared for the US Congress by the National Toxicology Program in response to Section 301 (b) (4) of the Public Health Service Act, as amended. The intent of the document is to provide a listing of those agents, substances or exposure circumstances which are either "known" or "reasonably anticipated" to cause cancer in humans, and to which a significant number of people in the United States are exposed. The first edition of the report (then known as the Annual Report on Carcinogens) was published in 1980, and similar criteria and review processes were used to consider nominated substances for listing through preparation of the 7th edition published in 1994. In 1994 Dr. Ken Olden, Director of NTP and NIEHS established an ad hoc working group of the NTP Board of Scientific Counselors and charged them to review and make recommendations on two issues: the adequacy of the existing criteria and the incorporation of mechanistic data as part of the criteria for listing substances in future Reports. In addition Dr. Olden directed that the process used to review nominations for listing in or delisting from the Report be revised to allow more public input throughout the process and to add external review to broaden the scope of scientific review. As a consequence, in 1994 and 1995 the criteria were examined by a panel whose membership included academia, industry, labor, public/environmental organizations, state and local health departments and government who met in public session in public meetings. Recommendations were made for revising the evaluation listing criteria and the nomination review process which were approved by the Secretary, HHS on September 13, 1996 [Federal Register: September 26, 1996, Volume 61, Number 188, Page 50499-50500]. The substances newly included in the 8^th edition of the Report on Carcinogens (1998) and the nominations for listing in or delisting from the 9^th edition were evaluated using these revised review process and criteria.

Public Review and Comment Encouraged

A panel to include NTP staff and representatives of the NTP Board of Scientific Counselors and the NTP Executive Committee will receive comments and participate in the discussion. NTP staff will summarize the process and the evaluation listing criteria. Presentations from the panel will be tentatively from 9 ¿ 10 a.m. The remainder of the time will be devoted to public comment and discussion.

The NTP welcomes the continued and meaningful input from all stakeholders in reviewing the RoC process and the listing criteria as we move forward to the 10^th edition of the RoC. The experience and perspectives of all stakeholders are critical to ongoing evaluations of nominations to the RoC.

Written comments are welcome and can be sent to the address given below. Written comments must include name, affiliation, mailing address, phone, fax, e-mail, and sponsoring organization (if any). Comments received by September 15 will be considered for their implications with respect to the reviews of nominations for the 10th edition of the RoC and the December 16-17, 1999, public review.

Oral comments may be presented to the panel described above. Each speaker will be asked to identify their sponsoring organization (if any). The time allotted for each presentation will be largely dependent upon the number of individuals who register to speak at this one day meeting. Speakers will be registered and assigned time on a first-come, first-serve basis. Registration to speak at this meeting will be accepted until the 9 am start of the meeting. It is anticipated that at least 10 minutes will be available for each presenter to address the panel. When oral comments are read from printed copy, it is requested that 10 copies of the text be provided when registering at the meeting to be distributed to the panel members and to supplement the record of the meeting.

RoC Listing/Delisting Procedures and Listing Criteria:

The current procedures and review listing criteria follow this announcement. Revised criteria were announced first in the Federal Register and other publications in 1996 [Federal Register: September 26, 1996, Volume 61, Number 188, Page 50499-50500] and clarified in the FR and other publications in April 1999 (FR Vol. 64, No. 63 pp 15983-15984 and Vol. 64, No. 74; pp 19188-19189). The procedures and criteria can also be found on the NTP website located at www.ntp.niehs.nih.gov.

Registration for Meeting

Registration Pre-registration to attend this meeting can be made by notifying Ms. Angie Wilson by mail at NIEHS, Building 101, Room A328, P.O. Box 12233, Research Triangle Park NC 27709, by phone at (919) 541-3971, by FAX at (919) 541-0295, or by e-mail at wilson9@niehs.nih.gov. Please indicate if you wish to make an oral presentation. On site registration on site will be available the morning of September 15, 1999 from 8:30 am to the 9:00 am. start of the meeting. If possible, those wishing to speak should provide a written copy of their statement no later than September 13, 1999before the September 15^th meeting, to permit copying for the panel members. Those registering on site are requested to provide 10 copies of their statement for distribution to the panel and to supplement the record of the meeting. Written statements should supplement and may expand on the oral presentation, or may be submitted in lieu of an oral presentation. When registering to comment, please provide your name, affiliation, mailing address, phone, fax, e-mail, and sponsoring organization (if any).

Date/signed: July 1, 1999

Kenneth Olden, Ph.D.
Director, NTP and NIEHS

[Billing Code 4140-01-P]

REPORT ON CARCINOGENS
LISTING/DELISTING PROCEDURES

Petitions for listing or delisting an agent, substance, mixture, or exposure circumstance in the Report on Carcinogens (RoC) should be submitted to the National Toxicology Program (NTP)¹. Nominations 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 nomination should be provided or referenced.

An agent, substance, mixture, or exposure circumstance nominated for listing or delisting will be announced in the Federal Register, trade journals, and NTP publications to solicit public comment. The original nomination and all comments received will be evaluated by a National Institute of Environmental Health Sciences (NIEHS/NTP) Report on Carcinogens Review Committee (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 nomination warrants formal consideration, the NTP may initiate an independent search of the literature and prepare a draft review document for the substance under consideration. Draft documents will be prepared according to the following general format:

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

FORMAL REVIEW STEPS

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

NIEHS/NTP Review Committee for the Report on Carcinogens (RG1)

The original nomination and all public comments received in response to a nomination will be reviewed by RG1. Assignment of a primary and secondary reviewer will be made upon receipt of a nomination. Reviewers will lead discussions concerning the adequacy of the nomination. If the nomination warrants formal consideration, a search of pertinent databases will be performed and available citations will be reviewed by the primary reviewer. The primary reviewer will identify the relevant articles. After consultation with the secondary reviewer, the identified literature will be obtained and a draft summary of all available information from the original nomination and the literature search will be prepared. The primary and secondary reviewers will examine the nomination, 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 nominations will also be considered. The RG1 will make a formal recommendation for those nominations determined to contain sufficient information for listing or delisting in the RoC. The nomination then continues through the review process.

Nominations reviewed by RG1 for which sufficient information could not be obtained will not proceed further. The other RoC review groups, as well as the NTP Executive Committee, will be informed of this action. The original nominator will be notified of the RG1 action and invited to resubmit the nomination with additional justification. All nominated agents, substances, or mixtures reviewed by RG1 but not selected for listing or delisting will be included in the subsequent edition of the RoC with the reason(s) why they were not considered further.

NTP Executive Committee's Interagency Working Group for the Report on Carcinogens (RG2)

The second review phase of nominations will be done by the NTP Executive Committee's Interagency Working Group for the Report on Carcinogens (RG2). RG2 is a Governmental interagency group that assesses whether relevant information on the nominated agent, substance, or mixture is available and sufficient for listing in or delisting from the RoC. A reviewer for each nomination will be assigned from the RG2 who will be responsible for reviewing the draft document and for leading the Working Group's discussion of the nomination. Public comments received in response to announcements of nominations 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 recommendation for listing or delisting. The nomination then continues through the review process.

Board of Scientific Counselors RoC Subcommittee (External Peer Review)

The third review phase for nominations will be performed by a subcommittee of the NTP Board of Scientific Counselors. This subcommittee serves as another independent peer review group that assesses whether the relevant information available is sufficient for listing in or delisting. The NTP Board RoC Subcommittee will review nominations in a public meeting. Prior to public review, a notice will be published in the Federal Register, trade journals, and NTP publications, soliciting public comment. The notice will also invite interested groups or individuals to submit written comments and/or to address the NTP Board RoC Subcommittee during the review meeting. Reviewers for each nomination will be assigned from the NTP Board RoC Subcommittee who will be responsible for reviewing the draft document and leading the subcommittee's discussion of the nomination. Upon completion of its review, NTP Board RoC Subcommittee will provide comments and recommendations for any changes and/or additions to the draft document and also make its formal recommendation for listing or delisting the nominated agent, substance, or mixture.

Upon completion of the reviews by RG1, RG2, and NTP Board RoC Subcommittee, those nominated agents, substances, mixtures, or exposure circumstance which are recommended for listing in or delisting from the RoC, 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 independent recommendations of RG1, RG2, and NTP Board RoC Subcommittee and all public comment will be presented to the NTP Executive Committee² for review and comment.

NTP Director

The Director, NTP receives the four independent recommendations from RG1, RG2, NTP Board RoC Subcommittee, and the NTP Executive Committee and makes the final decision regarding the proposed listing and/or delisting and submits the RoC to the Office of the Secretary, DHHS. Upon review and approval by the Secretary, DHHS and submission to Congress, a notice of the RoC publication, indicating all newly listed or delisted agents, substances, mixtures, or exposure circumstance will be published in the Federal Register, trade journals, and NTP publications.

² Agencies represented on the NTP Executive Committee include:
Agency for Toxic Substances and Disease Registry (ATSDR), Consumer Product Safety Commission (CPSC), Environmental Protection Agency (EPA), Food and Drug Administration (FDA), National Center for Toxicological Research (NCTR), 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), National Library of Medicine (NLM), and National Institute of Environmental Health Sciences/NTP (NIEHS/NTP)

Report on Carcinogens
Criteria for Listing Agents, Substances or Mixtures

1. Known to be Human Carcinogens:

   There is sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer.

    

2. Reasonably Anticipated to be Human Carcinogens:

   There is limited evidence of carcinogenicity from studies in humans which indicates that causal interpretation is credible but that alternative explanations such as chance, bias or confounding factors could not adequately be excluded; or

   There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors: (1) in multiple species, or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site or type of tumor or age at onset; or

   There is less than sufficient evidence of carcinogenicity in humans or laboratory animals, however; the agent, substance or mixture belongs to a well defined, structurally-related class of substances whose members are listed in a previous Report on Carcinogens as either a known to be human carcinogen, or reasonably anticipated to be human carcinogen or there is convincing relevant information that the agent acts through mechanisms indicating it would likely cause cancer in humans.

Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment, with consideration given to all relevant information. Relevant information includes, but is not limited to dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub populations, genetic effects, or other data relating to mechanism of action or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would therefore not reasonably be anticipated to cause cancer in humans.