National Toxicology Program

Background

Section 301(b)(4) of the Public Health Service Act, as amended, provides that the Secretary, Department of Health and Human Services (DHHS), shall publish a report which contains a list of all substances (1) which either are known to be human carcinogens or may reasonably be anticipated to be human carcinogens, and (2) to which a significant number of persons residing in the United States (US) are exposed. Within the Department of Health and Human Services, the Secretary has delegated the responsibility for preparing these reports to the National Toxicology Program (NTP). The Report on Carcinogens (RoC) is an informational scientific and public health document that identifies and discusses agents, substances, mixtures, or exposure circumstances that may pose a carcinogenic hazard to human health. It serves as a meaningful and useful compilation of data on the (1) carcinogenicity, genotoxicity, and biologic mechanisms of the listed substances in humans and/or animals, (2) the potential for exposure to these substances, and (3) the regulations promulgated by Federal agencies to limit exposures.

In 1994, the NTP Director initiated a review of the RoC to 1) broaden the input to the preparation of the Report, 2) broaden the scope of scientific review associated with the RoC, and 3) provide review of the criteria used for listing substances in the RoC. The criteria review was open to the public and included participation of, or input from, a broad base of interested parties including academia, industry, labor, private organizations, and Federal, State, and local agencies. In 1996, revised criteria, which allow for listing decisions to be made with consideration given to all relevant information including mechanism of action, were approved by the Secretary, and the NTP Director announced revisions to the process for reviewing nominations for listing or delisting in the RoC. The revised process included addition of an external peer review to be conducted in public meetings with opportunity for public comment; allowed for additional public input throughout the review process; and established a formal mechanism for delisting substances from the RoC. The revised process and criteria were used in the preparation of the 8^th RoC published in 1998 and in the review of nominations for the 9^th Report, published in 2000.

During the preparation and review of the 8^th and 9^th RoC, the NTP received comments from interested stakeholders on proposed listings, the process and procedures used in the review, and the criteria for listing/delisting. The NTP has been deliberate in its efforts to solicit public input and to understand the concerns of stakeholders. The NTP has encouraged dialogue with stakeholders and responded, primarily in writing, to individual concerns and requests for additional information. The NTP did not hold meetings with individual stakeholders regarding their concerns because the closed nature of individual meetings is in conflict with the open review process established for the RoC. At the request of a private organization, the Toxicology Forum, the NTP staff attended its meeting in July 1999 and chaired a session on the RoC, which included an NTP panel to receive and respond to questions and comments from the attendees. The NTP also held a public meeting in October 1999 in an effort to obtain the broadest base of input and to provide all interested parties an opportunity to express their views about the review process and/or the evaluation criteria. The goal of the meeting was to create a dialogue among the stakeholders and NTP, and time was allotted for participants to present their views and to comment on the views expressed by others during the meeting. The meeting was chaired by Dr. Bernard Goldstein, Director of the Environmental and Occupational Health Sciences Institute of Rutgers and the University of Medicine and Dentistry of New Jersey. Assisting Dr. Goldstein with the identification of issues being presented were two NTP Board of Scientific Counselor members, Dr. Clayton Frederick, Rohm and Haas; and Dr. Lynn Goldman, Johns Hopkins University. Also attending were the NTP Director and his key NTP staff and other representatives from the Board of Scientific Counselors (BSC) and from each of the review groups involved in the Report's preparation. Forty-one persons registered to speak at the public meeting and they included private citizens, representatives of industry, organized labor unions, public citizen organizations, and law firms.

Public Comments and the NTP's Response

In summary, some comments received suggested that the current listing process is flawed and does not always include the best science. These comments also suggested that submission of the 9^th RoC to the Secretary, DHHS, be delayed pending a re-review of specific substances by a revised process that contains their suggested improvements for the reviews. Other comments noted that the current process is open, scientifically sound, and fair and declared that the 9^th Report should go forward as soon as possible. The NTP believes that the procedures and criteria used for review of nominations in the 9^th RoC are basically sound and concluded that there were no issues or problems identified that should delay publication of the 9^th Report.

The NTP is committed to maintaining an open and transparent process for preparation of the RoC that is unencumbered by special interests; includes high quality and open scientific review of substances nominated for listing/delisting; uses the best, publicly available, peer reviewed science; and allows for stakeholder input at multiple levels. However, public input did identify some areas where procedural modifications, as noted below, would strengthen the review process, enhance stakeholder involvement, and improve communication and outreach efforts. The NTP greatly appreciates the input from all parties and will move forward in implementing some changes immediately while considering other recommendations for possible implementation in the future. In making these changes to the RoC's preparation and review, the NTP is committed to providing the resources needed to ensure their successful implementation.

NTP's responses to comments

1. In response to suggestions for earlier and more thorough notification of stakeholders, the NTP will identify to the extent possible, key scientific issues related to individual nominations and communicate them publicly when nominations are initially announced. This notification will occur at least six months prior to the BSC RoC Subcommittee's review. Stakeholders will be invited to provide written comments addressing these issues and also to identify any additional issues. This early input from stakeholders will help to ensure that all issues critical to evaluating the listing/delisting are addressed during development of the background documents and are considered throughout the review process.

2. In reply to the suggestion that the NTP respond to individual comments, the NTP will continue to revise the background documents during the deliberations by Review Groups 1 and 2 (RG1 and RG2, respectively). Following completion of RG2's review, the background documents are considered the document of record and will not be changed in response to any subsequent stakeholder input except to correct errors. The NTP will make public comments received on all nominations available on its world-wide-website. All comments received by published deadlines will continue to be made available to the BSC RoC Subcommittee for its use in the review of nominations. All comments received will also be provided to the NTP Executive Committee and the NTP Director. A summary of stakeholder opinion for each nomination will also continue to be provided to the Secretary.

• In response to the concerns expressed about unevenness in the quality of the background documents, the NTP will expand the use of external, compound-specific experts in their preparation. In addition, these experts will now be invited, as needed, to participate in the BSC RoC Subcommittee's meetings and discussions as well. Such situations would include instances where the experts contribute significantly to preparation of the background document or where the scientific issues for the nomination are unusually complex and/or controversial. The NTP believes that this addition of compound-specific expertise will strengthen the BSC RoC Subcommittee's review of the nominations.

• In response to concerns regarding the need to increase the time allotted for public review and comment on the background documents, the NTP will make background documents available eight weeks prior to the BSC RoC Subcommittee meeting. The deadline for receipt of public comments will be two weeks prior to the BSC RoC Subcommittee's meeting and review. Comments submitted following the deadline would be included with the materials assembled on the nominations and evaluated by the NTP, the NTP Executive Committee, and the NTP Director.

• Beginning with the 10^th Report, the NTP will increase the time allotted at the BSC RoC Subcommittee meeting for presentation of each stakeholder's comments on a nomination from five minutes to a minimum of seven minutes, and depending upon the number of public comments and the time available, this will be increased to ten minutes when requested. Speakers will continue to be invited to submit written comments to supplement their oral presentation.

• As suggested at the October public meeting, the NTP will hold the next few BSC RoC Subcommittee meetings in the Washington, D.C. area to make the meetings more accessible to all stakeholders. After that time, the NTP will evaluate whether this effectively increases public participation. The January 2000 Subcommittee meeting was moved from NTP headquarters in North Carolina to the Crystal City Marriott in Arlington, VA.

• The NTP has evaluated the suggestion that the RoC attempt to communicate more fully the conditions under which exposure to a listed substance might be anticipated to cause cancer in humans. Currently, the doses of substances associated with cancer in experimental animal or human epidemiology studies are clearly indicated in RoC background documents, and dose response characteristics are an important consideration in establishing a link between exposure to a substance and cancer. The RoC also provides general information about human exposures, when available. The NTP believes that the Report's current level of emphasis on dose is appropriate and efforts to characterize exposures associated with cancers in greater detail would go beyond its intended focus on hazard identification and into the arena of quantitative risk assessment.

Issues under consideration

• The NTP will formally consider a recommendation that proposes creating separate groupings of substances within the RoC according to their intended use. Pharmaceuticals would be an example of a special grouping. Consideration would be given to other groupings based on use categories to improve the utility of the document. Formal consideration of this recommendation will include solicitation of public comments and review by the NTP's RoC Review Committees and the NTP Executive Committee.

• The NTP will ask the applicable regulatory agencies to consider communicating during the review process, information about the possible regulatory implications of listing or delisting a substance or exposure circumstance in the RoC. Currently, the RoC provides information about any existing Federal regulatory standards for a listing. This information is part of the profile for each listing and is updated with each edition of the Report. It is anticipated that these communications from the applicable regulatory agencies could lead to a better understanding by the public of the potential regulatory implications of a listed or delisted substance.

• The NTP will work with regulatory agencies to identify additional venues and strategies for targeting communication about the RoC with the broad group of stakeholders, including trade groups, and soliciting their input. Currently, information dissemination is reasonably broad-based through the NTP world-wide-website and list server, Federal Register notices, NTP newsletter, press advisories, and the Environmental Health Perspectives, a scientific environmental health research journal.

Comments or Questions should be directed to the
NTP Liaison and Scientific Review Office at:
Telephone: (919) 541-0530; Fax (919) 541-0295
e-mail: Send Email

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