National Toxicology Program

NTP Response to Comments Received on the Draft Report on Carcinogens Review Process

In August 2006, the National Toxicology Program (NTP) released the draft process for preparation of the 12^th Report on Carcinogens (RoC) and invited public comment (71FR47507). NTP received six public comments from the groups listed below, which were posted on the RoC webpage at http://ntp.niehs.nih.gov/go/28651:

Styrene Information and Research Center
North American Insulation Manufacturing Association
Cosmetic, Toiletry, and Fragrance Association
Naphthalene Council
American Chemical Council
Center for Regulatory Effectiveness

All comments voiced support for NTP's efforts to improve the scientific review process. This document addresses issues raised in the public comments and the NTP's response. Some comments suggested the addition of elements or steps that are already part of the proposed RoC review process. These include:

• The expert panel¹ will be composed of scientists with expertise and knowledge relevant for evaluating the candidate substance.
• The public will be invited to suggest names of scientists to serve on the expert panels.
• All public comments will be posted on the RoC website and distributed to the relevant review group before its meeting.
• Draft substances profiles² will be released to the public for comment.
• The current RoC criteria (available at http://ntp.niehs.nih.gov/go/15209) will be used for evaluation of candidate substances.
• All review groups will be charged to apply the RoC criteria to the relevant scientific evidence when evaluating the carcinogenic potential of a candidate substance. The criteria provide for consideration of weight of evidence, mechanistic data, and mode of action.

Some comments suggested changes to specific elements or steps in the draft RoC review process. These issues are grouped by topic area and addressed below.

Nominations and Selection of Candidate Substances

• The review process does not address delisting or removal of a listing from the RoC.

• Nominations and their supporting information should be made publicly available online as soon as they are received.

NTP Response: Following an internal review of the nominations and their supporting documentation, NTP will announce the nominations proposed for review in the Federal Register and NTP publications.

• What does "lack of sufficient information for applying the listing criteria" mean in relation to a nomination to the RoC? It should mean that a substance proposed for review would not be reviewed if internal staff review or external comment shows that the substance is neither known nor reasonably anticipated to be a human carcinogen.

NTP Response: "Lack of sufficient information" means that adequate studies (such as animal, human or mechanistic), which are critical for evaluation of the substance's carcinogenicity, are not available in the peer-reviewed literature. Lack of information does not imply that the substance is or is not a known or reasonably anticipated to be human carcinogen. Decisions about listing status for a candidate substance are made after completion of the formal scientific review process. NTP added a footnote to the RoC process to define "lack of sufficient information."

Draft Background Documents

• NTP should review and respond to public comments on the draft background document and provide that response to the expert panel prior to the meeting and, if necessary, revise the background document before the expert panel meeting.

NTP Response: One purpose of the expert panel meeting is to gain expert scientific input regarding whether changes are needed to the draft document. NTP will instruct the expert panel to review and consider all public comments in its peer review of the background document. Following the meeting, NTP will consider the expert panel's peer review comments and the public comments that address factual and technical issues in the draft background document. The final background document will reflect NTP's response to those remarks.

• The requirement to include only publicly available, peer-reviewed literature in sections 3 to 5 of the draft background documents could limit availability of information. The expert panel should be asked to review unpublished data finalized in the 2 years prior to publication of the draft background document to determine whether that data would impact the listing decision for a substance.

NTP Response: NTP requires publicly available, peer-reviewed data in sections 3 to 5 of the background document to ensure its scientific integrity.

• Data used to prepare sections 1 and 2 of the draft background document should have to come from publicly available, peer-reviewed sources.

NTP Response: Section 1 of the background document describes the chemical and physical properties of the candidate substances and section 2 describes information related to human exposure such as use, production, export and import data, environmental occurrence, regulations, etc. NTP does not require that the data used for these sections come from peer-reviewed sources, because they generally are not provided in peer reviewed publications; however, peer-reviewed data are preferred whenever possible. The data must be publicly available, and the NTP will list all references in the background document and provide a copy of a reference upon request.

Expert Panel Meeting

• NTP should publish the names and areas of expertise of proposed members of expert panels and invite the public to comment as the National Academy of Sciences does.

NTP Response: NTP will invite the public to suggest names of scientists to serve on the expert panels. Final selection of members to serve on these panels will be made in accordance with the Federal Advisory Committee Act and Department of Health and Human Services (HHS) implementing regulations. NTP is following a process that has proven effective for establishing these panels and inviting comment on the expert panel is not needed to ensure the quality of the review. NTP will include a roster of the expert panel members and their affiliation on the webpage for each meeting along with other relevant information such as the panel's charge, draft background document, and public comments.

• NTP should clearly establish the permissible roles and responsibilities of the expert panel members and NTP Board of Scientific Counselors (BSC)³ versus the public commenters.

NTP Response: NTP agrees that the roles and responsibilities of members of the different review groups should be clearly defined in their charge and evident to those in attendance.

• The expert panel report should address all public comments.

NTP Response: The expert panel will receive any written comments submitted to the NTP prior to the expert panel meeting. In addition, the public can provide oral and/or written comments at the meeting. NTP will instruct the expert panel to consider all relevant public comments (both oral and written) in their deliberations. The expert panel report will capture the panel's discussion of any comments that are addressed.

• NTP should release its response to the expert panel report as soon as it is available and provide it to the BSC. NTP's response to the expert panel report should address the expert panel's recommendation on listing status and the public comments.

NTP Response: The final background document will reflect NTP's consideration of the expert panel's peer review comments on factual and technical issues in the draft background document. NTP will release its response to the expert panel's peer review report when the RoC is made public. This response to the expert panel report will not address the expert panel's recommendation for listing status of the candidate substance in the RoC or its scientific justification for that recommendation to ensure that the review process is open, and impartial. On a trial basis for the 12^th RoC, NTP will prepare a response to public comments received following release of the expert panel report; this response is released when the RoC is made public.

Internal Reviews by the Government

• The meetings of the Interagency Scientific Review Group and the National Institute of Environmental Health Sciences/NTP Scientific Review Group should be open to the public or there should be a public written record.

NTP Response: Meetings of these two government review groups are not subject to the Federal Advisory Committee Act and their meetings or deliberations will not be public.

Peer Review of Draft Substances Profiles

• NTP should invite the NTP Board of Scientific Counselors (BSC) to comment on the NTP's listing decision as well as its scientific justification for listing.

NTP Response: Historically, NTP asked a subcommittee of the BSC for its opinion on the listing status of candidate substances; the expert panels will now have this role. The RoC review process defines a new role for the BSC. The BSC's charge will be 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 status in the RoC. The NTP will not ask the BSC to comment on its policy decision regarding listing status of the candidate substance.

• NTP should conduct all portions of BSC meetings in public session.

NTP Response: NTP favors an open and transparent process and has decided to hold the entire BSC meeting for peer review of the substance profiles open to the public.

Preparation of Draft RoC and Transmittal

• The public should have an opportunity to comment on the draft/proposed RoC.

NTP Response: The draft RoC is a pre-decisional document submitted to the Secretary, HHS, for review and approval and will not be released to the public for comment.

Availability of Draft Documents

• NTP should increase the time from 45 to 60 days that the draft background documents or draft substance profiles are available to the public prior to the expert panel or NTP Board of Scientific Counselors (BSC) meeting, respectively.

NTP Response: NTP accepts this suggestion and revised the RoC review process to increase the time from 45 to 60 days that either draft document is released to the public prior to the relevant public meeting.

Public Comments

• The NTP should provide sufficient time at the public meetings of the expert panels or NTP BSC for a full discussion of the candidate substances and for the public commenters to make their presentations and respond to questions from the review group.

NTP Response: NTP concurs that the meetings of the expert panels or BSC should provide adequate time for them to discuss the candidate substances. The time for each candidate substance will be determined on an individual basis taking into consideration the complexity of the scientific data and the number of public speakers who preregister. The public meetings of these review groups will include time for the public to make oral comments and for the expert panel or BSC to ask questions of the speakers, if desired.

• NTP should respond to public comments throughout the process and make them available to the expert panel or BSC prior to the relevant meeting. NTP should continue preparation of a response to comments document for all future RoC.

NTP Response: NTP on a trial basis for the 12^th RoC will prepare a response to public comments received following release of the expert panel report and will make this response available when the RoC is released publicly. NTP will assess the merit of responding to public comments following completion of the 12^th RoC and determine whether any change is needed in the review process with regard to this practice. NTP does not plan to release its response to public comments prior to public release of the RoC to ensure that the review process remains open, and impartial.

Listing Criteria

• NTP should consider additional categories for evaluating candidate substances for the RoC.

NTP Response: The congressional mandate for the RoC restricts the classification of substances in the report to two categories: known to be a human carcinogen and reasonably anticipated to be a human carcinogen.

Information Quality Act

• NTP official should certify in the administrative record for each RoC that the Information Quality Act pre-dissemination review requirements have been met and provide a brief explanation about how they were met.

NTP Response: The Information Quality Act does not require a formal certification, but as with other HHS programs, NTP works to ensure that the Information Quality Act guidelines, including those for pre-dissemination peer review, are met.

__________________

¹An expert panel is an ad hoc group of scientists with relevant expertise and knowledge selected by the NTP from the public and private sectors. Nominations to serve on specific expert panels are solicited from federal and nonfederal sources. The final selections for membership are based upon providing a balanced and unbiased group of highly qualified individuals and are made in accordance with the Federal Advisory Committee Act and HHS implementing regulations.
²The RoC contains substance profiles for each candidate substance. Full substance profiles are developed for "known" and "reasonably anticipated" human carcinogens and contain the listing status, summarize the scientific information that supports the recommendation, and provide information on use, exposure and production. Limited substance profiles are developed for candidate substances "not listed" in or "delisted" from the RoC and vary in content on a case-by-case basis.
³The BSC is a federally chartered advisory committee whose members are appointed by the Secretary, HHS. The BSC provides advice to the NTP Director on matters relating to scientific program content and evaluates the scientific merit of the NTP's intramural and collaborative programs.