National Toxicology Program

A nomination for listing or delisting in the 11th RoC was evaluated initially by the NIEHS / NTP Review Group (RG1), composed of senior scientists from the NIEHS / NTP staff, to determine if the information provided indicated that the nomination warranted further consideration by the NTP . If it was determined that the submitted nomination did not contain sufficient information to warrant consideration, it was returned to the original nominator who was invited to resubmit the nomination with additional justification, which may include new data, exposure information, etc. The NTP Executive Committee and the NTP Board of Scientific Counselors were informed of all nominations not accepted for review for listing or delisting in the RoC.

The NTP solicited public comments on all nominations accepted for review through announcement in the Federal Register and NTP publications. The NTP initiated an independent search and review of the literature and prepared a background document for each nomination under consideration. The background documents were prepared with the assistance of a consultant or a panel of consultants who have expertise and/or knowledge for the specific nomination that was relevant to its evaluation of carcinogenicity. Background documents were prepared according to the following general format:

1. Introduction
   Information contained in this section includes chemical identification such as synonyms, trade names, CAS Registry numbers, molecular formula, molecular structure, etc. Also included are physical-chemical properties and identification of structural analogs or metabolites.


2. Human Exposure
   Information contained in this section can include use; production; analysis; environmental occurrence including environmental release, drinking water and food content and occurrence in consumer products; environmental fate in air, water, and soil; environmental and occupational exposures; biological indices of exposure; and regulations including occupational exposure limits and "other" standards and criteria.


3. Human Studies
   Information contained in this section can include traditional cancer epidemiology investigations including case control and cohort studies as well as data from clinical studies.


4. Experimental Carcinogenesis
   Information contained in this section can include experimental animal investigations of potential carcinogenesis including long term bioassays, experiments where the substance is administered in conjugation with known carcinogens or factors that modify carcinogenic effects, studies to investigate a defined precancerous lesion and experiments on the carcinogenicity of known metabolites and derivatives.


5. Genetic Related Effects
   Information contained in this section can include investigations of genetic and related effects including gene mutation and chromosomal damage.


6. Other Data Relevant to Evaluation of Carcinogenicity and its Mechanisms
   Information contained in this section can include metabolism, absorption, distribution and excretion of the substance, other toxic effects, and data derived from the study of tissues or cells from humans and/or experimental animals exposed to the substance in question, which can be useful for evaluating whether a relevant cancer mechanism is operating in people.

Data used in the preparation of Sections 3 through 6 of the background document must come from publicly available, peer-reviewed sources. In special cases, the review groups listed below may be asked to provide formal peer-review for a document the NTP deems to be important to the review but has otherwise not received peer-review; such a document would need to be publicly available.

FORMAL REVIEW STEPS

Nominations under consideration by the NTP for listing in or delisting from the RoC undergo a multi-step, scientific review process that includes several opportunities for public comment. The following text briefly describes that process.

NIEHS / NTP RoC Review Committee (RG1)

The RG1, composed of senior scientists from the NIEHS / NTP staff, conducts the initial review of a nomination for listing in or delisting from the RoC and in that review, considers all public comments received in response to the announcement of the nomination. The RG1 first reviews the background document prepared for the nomination and determines if it is adequate for use in reviewing the nomination and for applying the criteria for listing in the RoC. Upon acceptance of the background document, it is then considered the final document of record. The RG1 then proceeds with scientific review of the nomination and makes a recommendation for listing or delisting in the RoC. After the background document becomes the final document of record, it is placed on the NTP RoC website with a notice published on the NTP list-server and the NTP website announcing its availability.

It is possible that the RG1 review of the background document for a nomination may determine that there is insufficient relevant information to apply the criteria for listing in or delisting from the RoC. In this situation, the review of the nomination stops and the NTP will inform subsequent RoC review groups and the NTP Executive Committee of this action and why further review is not warranted. The original nominator is notified of the RG1 action and is invited to resubmit the nomination with additional relevant information and justification. All nominations not reviewed beyond RG1, because of the lack of sufficient relevant information, are 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 RoC (RG2)
The RG2, a governmental interagency scientific review group, conducts the second review of nominations to the RoC. The RG2 assesses whether relevant information for a nomination is available and sufficient for listing in or delisting from the RoC. The RG2 reviews the original nomination and all public comments received in response to announcements of nominations accepted for review. Upon completion of its review, the RG2 provides comments and makes its recommendations for listing or delisting the nominations in the RoC.

Board of Scientific Counselors RoC Subcommittee (External Peer Review)
The third step in the review process is external scientific peer review of the nominations by a standing subcommittee of the NTP Board of Scientific Counselors ("the RoC Subcommittee"). The RoC Subcommittee serves as an independent peer review group that assesses whether the relevant information available for a nomination is sufficient for listing or delisting it in the RoC. The RoC Subcommittee reviews nominations in an open public meeting. Prior to this public review, a notice is published in the Federal Register and NTP publications announcing the meeting and the availability of the background documents and soliciting public comment on the nominations. The notice invites interested groups or individuals to submit written comments and/or address the RoC Subcommittee during the public review meeting. Upon completion of its review, the RoC Subcommittee provides comments and makes its recommendations for listing or delisting the nominations in the RoC.

Final Public Comment
Upon completion of the reviews by RG1, RG2 and the RoC Subcommittee, the NTP publishes the nominations and the review groups' recommendations for each (to list, to delist, or not to list in the RoC), and solicits the third and final public comment and input on the nominations.

NTP Executive Committee
The recommendations of RG1, RG2 and the RoC Subcommittee and all public comments received to date are presented to the NTP Executive Committee² for review and comment. The NTP Executive Committee reviews the information on the nominations and provides its opinion for listing or delisting them in the RoC.

NTP Director
The NTP Director receives the independent recommendations for the nominations from RG1, RG2 and the NTP Board RoC Subcommittee, the opinion of the NTP Executive Committee and all public comments received concerning the nominations. The NTP Director evaluates this input and any other relevant information on the nominations and develops recommendations to the Secretary, Department of Health and Human Services (DHHS) regarding whether to list, delist, or not list the nominations in the RoC.

Secretary, Department of Health and Human Services (DHHS)
The NTP prepares a final draft of the RoC based on the NTP Director's recommendations and submits it to the Secretary, DHHS for review and approval. Upon approval of the RoC, the Secretary submits it to the U. S. Congress as a final document. The submission of the RoC to Congress constitutes publication of the report and it becomes available to the public at that time. The NTP publishes a notice of the publication and availability of the latest edition of the RoC, indicating all newly listed or delisted agents, substances, mixtures or exposure circumstances in the Federal Register and NTP publications.