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November 1, 2011

NTP Proposes to Revise RoC Review Process

The ACTA Group

The National Toxicology Program (NTP) published an October 31, 2011, Federal Register notice inviting written comments on its proposed Report on Carcinogens (RoC) review process and announcing a public listening session to receive oral comments. 76 Fed. Reg. 67200. The RoC is a Congressionally mandated, biennial document that identifies agents, substances, mixtures, or exposure circumstances that may pose a hazard to human health by virtue of their carcinogenicity. Substances are listed in the report as either known or reasonably anticipated human carcinogens, and NTP includes a description of the substance, its uses, potential sources of exposure, the rationale for listing, and applicable federal regulations in a substance profile. According to the Federal Register notice, NTP is proposing changes to the RoC process to “enhance transparency and efficiency and to enable the NTP to publish the RoC in a timelier manner. The NTP also seeks to maintain critical elements of the existing process including external scientific and public involvement, scientific rigor, and external peer review.” Although the RoC is intended to be a biennial document, that has not been the case. NTP most recently published the 12th RoC in June 2011. It published the 11th RoC in 2005. NTP will hold a public listening session on the proposed review process on November 29, 2011, and the deadline to register for the session is November 21, 2011. Written comments on the proposed review process are due November 30, 2011. More information is available online.

NTP’s proposed RoC review process has four parts: (1) nomination and selection of candidate substances; (2) scientific evaluation of candidate substances; (3) public release of the draft RoC monograph and peer review; and (4) Health and Human Services (HHS) approval and release of the latest edition of RoC. Each part is described below. Differences from the review process for the 12th RoC, which is available online, are noted.

Nomination and Selection of Candidate Substances

NTP invites nominations of substances for consideration for listing in the RoC. A nomination may seek to list a new substance in the RoC, reclassify the listing status for a substance already listed, or remove a substance already listed. A nomination should contain a rationale or reason for the RoC review and, if possible, appropriate background information and relevant data to support the rationale.

The Office of the RoC (ORoC) initially evaluates the nomination to determine whether there is sufficient information on exposure and carcinogenicity to justify its formal evaluation and consideration for the RoC. Under the proposed review process, ORoC then shares nominations with its agency partners, including the Consumer Product Safety Commission, Department of Defense, U.S. Environmental Protection Agency, Food and Drug Administration, National Cancer Institute, National Center for Environmental Health/Agency for Toxic Substances and Disease Registry, National Institute of Environmental Health Sciences (NIEHS), National Institute for Occupational Safety and Health, and Occupational Safety and Health Administration.

Under the proposed review process, ORoC prepares a concept document for each substance proposed for evaluation. The concept document outlines the rationale for the substance’s review for the RoC, and lays out the proposed approach for development of the cancer evaluation component of the draft RoC Monograph on the substance. NTP announces one or more proposed substances for evaluation and solicits public comments on draft concepts through announcements in the Federal Register and NTP publications. Under the process used to prepare the 12th RoC, NTP announced nominations proposed for review and solicited public comment and relevant information concerning carcinogenicity of the substance, as well as data on current production and information on exposure and patterns of use. NTP used the comments to refine the list of nominated substances to identify the candidate substances that would proceed through the full review process, and identify scientific issues that should be addressed in the preparation and/or review of the draft background document for an individual candidate substance.

In a new step, under the proposed review process, NTP presents the draft concept for a substance to the NTP Board of Scientific Counselors (BSC) at a public meeting with opportunity for public comment. The BSC is asked to comment on the draft concept for a proposed substance, including the rationale for its review for the RoC and the proposed approach for obtaining external scientific and public inputs in development of the cancer evaluation component of its draft RoC Monograph. NTP considers the BSC’s comments and public comments, and the NTP Director makes the final determination whether to add the substance to the list of candidate substances for RoC evaluation. Concepts for approved candidate substances are prepared in final based upon BSC comments and public comments and posted on the NTP RoC website.

Scientific Evaluation of Candidate Substances

Under the proposed review process, ORoC prepares a draft RoC Monograph for each candidate substance. The draft RoC Monograph has two parts: (1) a cancer evaluation component that applies the RoC listing criteria and recommends a listing status for the candidate substance; and (2) a substance profile containing NTP’s preliminary listing recommendation and a summary of the scientific evidence supporting that recommendation. Information on exposure and properties of the candidate substance must be publicly available. All scientific information used to evaluate the potential carcinogenicity of a candidate substance must come from publicly available, peer-reviewed sources. The process used to prepare the 12th RoC called for completion of a draft background document, which included the following sections: (1) introduction; (2) human exposure; (3) human cancer studies; (4) studies in experimental animals; and (5) other relevant data. Under the process for the 12th RoC, data used to prepare sections 3 through 5 must come from publicly available, peer-reviewed sources.

According to NTP, under the proposed review process, the nature, extent, and complexity of the scientific information on a candidate substance will guide its approach to develop the cancer evaluation component. The approach is tailored to enable ORoC to use the most appropriate mechanism(s) to obtain external advice and address scientific issues, and may vary among substances. The approach may include external scientific input (e.g., expert panel, workshop, individual technical advisors), public input (e.g., listening session, comment), and/or interagency input. All public comments received during the evaluation become part of the public record, are posted on the RoC website, and are considered by the NTP and/or any external advisors during subsequent steps in the process. Under the process for the 12th RoC, NTP convened an expert panel meeting for each candidate substance.

Under the proposed review process, ORoC completes the cancer evaluation component with consideration of all inputs to its development. Based on the cancer evaluation component, ORoC prepares the draft substance profile. These two documents are compiled to form the draft RoC Monograph. NTP requests comment on the draft RoC Monograph from its partner agencies. NTP considers this input and, as appropriate, prepares a revised draft RoC Monograph for public comment and peer review. Under the process used for the 12th RoC, following the expert panel meetings, NTP staff reviewed and considered the expert panel peer review comments and any public comments as it prepared the final background documents. Following the expert panel meetings, NTP went through “a number of reviews that are internal to the government to develop an initial listing status for each candidate substance to the RoC.” The internal review process for the 12th RoC was closed to the public, and consisted of separate meetings of two groups: (1) an interagency scientific review group; and (2) the NIEHS/NTP scientific review group.

Public Release of Draft RoC Monograph and Peer Review

Under the proposed review process, NTP releases the revised draft RoC Monograph for public comment and then convenes a meeting of an external advisory group (e.g., BSC or expert panel) to peer review the revised draft RoC Monograph. NTP publishes a Federal Register notice prior to the meeting announcing the peer review and availability of the revised draft RoC Monograph, and inviting written public comment. The public is also invited to attend the meeting and provide oral comments. The peer review charge is two-fold: (1) to comment on the cancer evaluation component, specifically, whether it is technically correct and clearly stated, whether NTP has objectively presented and assessed the scientific evidence, and whether the scientific evidence is adequate for applying the listing criteria; and (2) to comment on the substance profile, specifically whether the scientific justification supports NTP’s preliminary policy decision on the listing status of the candidate substance. A peer-review report of the deliberations by the expert panel or BSC is prepared and posted on the RoC website. The process used for the 12th RoC also included a peer review by the BSC, but the BSC was “charged to determine whether the scientific information cited in the draft substance profile for a candidate substance is technically correct, clearly stated and supports the NTP’s policy decision regarding its listing in the RoC.” NTP states that the BSC was “not asked to review the NTP’s decision regarding listing status.”

ORoC considers the peer-review report in concert with the NTP Director and prepares the final revised draft RoC Monograph on the candidate substance, including the cancer evaluation component and substance profile. NTP prepares a response to the peer-review report that is released to the public when the next edition of the RoC is released.

HHS Approval and Release of Latest Edition of RoC

Every two years, NTP submits newly reviewed candidate substances and their recommended listing status to the NTP Executive Committee for consultation, and then to the Secretary of HHS for review and approval. The substance profiles for new listings approved by the Secretary are added to the RoC, and the next edition of the report in electronic format is prepared, transmitted to Congress, and published on the RoC website. Periodically, NTP will publish the RoC in both printed and electronic formats, depending upon demand for the printed version. NTP publishes a notice in the Federal Register and NTP publications announcing the listing outcome for each candidate substance that underwent formal review for the RoC and the availability of the next edition of the RoC. At that time, the NTP posts its response to the peer-review report on the RoC website.

Next Steps

NTP will review both the written and oral comments on its proposed review process and consider what changes, if any, might be needed. According to the October 31, 2011, Federal Register notice, NTP intends to post the final RoC review process on the RoC website and present it at the next NTP BSC meeting on December 15, 2011. NTP will publish details about this meeting in the Federal Register and post them on the NTP website online.