[Federal Register Volume 68, Number 232 (Wednesday, December 3, 2003)]
[Notices]
[Pages 67692-67696]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-30122]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program: Announcement of a Public Meeting To 
Discuss the Review Process and the Listing/Delisting Criteria Used for 
the Report on Carcinogens

Summary

    The National Toxicology Program (NTP) announces a public meeting to 
receive public comment on the current process for reviewing nominations 
for listing in or delisting from the Report on Carcinogens (RoC) and on 
the current listing criteria used for evaluating the nominations. The 
purpose of this public meeting is to obtain input and provide all 
interested parties an opportunity to express their views about the 
review process for nominations to the RoC and/

[[Page 67693]]

or the evaluation criteria and to comment on the views expressed by 
others.
    The meeting will be held on January 27-28, 2004, at the Lister Hill 
Center Auditorium (Building 38A), National Library of Medicine, 
National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 
20892. The meeting will begin at 9 am on January 27 and will conclude 
by noon on January 28 or sooner if the public comments and discussion 
end earlier. On-site registration will begin at 8:30 am on January 27. 
Attendance at the meeting is limited only by the space available. 
Additional details about the meeting, including background information, 
agenda, written comments, registration and security information are 
provided below and are also available from the NTP Web site (http://ntp-server.niehs.nih.gov select NTP/RoC Public Meeting under What's 
New?).

Background

    The RoC is a public information document prepared by the NTP, 
pursuant to delegation from the Secretary of The Department of Health 
and Human Services (DHHS) as required by Section 301(b)(4) of the 
Public Health Service Act, as amended. The RoC provides 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 1st edition of the report (then known as the Annual Report 
on Carcinogens) was published in 1980. Similar criteria and review 
processes were used to consider/evaluate nominated substances for 
listing in the 1st through 7th editions; the 7th edition was published 
in 1994. In 1995, a panel whose membership included persons from 
academia, industry, labor, public/environmental organizations, state 
and local health departments and government met in public session(s) to 
examine the criteria. The panel recommended revisions to the listing 
criteria and the nomination review process for the RoC. The Secretary, 
DHHS approved the revised criteria on September 12, 1996 [61 FR 50499, 
September 26, 1996]. The revised criteria and review process were used 
to evaluate nominations to the 8th, 9th, and 10th editions of the RoC 
and are currently being used to evaluate nominations being considered 
for listing in or delisting from the 11th edition. A description of the 
proposed review process that will be used to evaluate nominations to 
future editions of the RoC and the listing/delisting criteria are 
provided below and can also be found on the NTP Web site (http://ntp-server.niehs.nih.gov/NewHomeRoc/AboutRoC.html).

Agenda

    A panel that includes NTP staff and representatives of the NTP 
Board of Scientific Counselors RoC Subcommittee, the NTP Executive 
Committee Interagency Working Group for the RoC and the NIEHS/NTP RoC 
Review Committee will receive the public comments and participate in 
the discussion.

Tentative Agenda

NTP/RoC Public Meeting

    Lister Hill Center Auditorium, National Library of Medicine, 
National Institutes of Health, Bethesda, Maryland.
January 27, 2004
8:30 a.m. Registration.
9 a.m. Welcome and Introductions; Overview of the history of the Report 
on Carcinogens, the proposed review process for nominations and the 
listing/delisting criteria; and Guidelines and procedures for oral 
comments and discussion.
10 a.m. Public comments (10 minutes per speaker, one speaker per 
organization).
5 p.m. Adjournment (The meeting may adjourn earlier if the public 
comments and discussion are finished.).
January 28, 2004
9 a.m. Continuation of public comments and discussion if not finished 
on January 27.
Noon Close of meeting (The meeting may close earlier if the public 
comments and discussion are finished.)

Public Comment Encouraged

    The NTP welcomes continued and meaningful input from all 
stakeholders concerning the RoC review process and the evaluation 
criteria used to list/delist nominations. The NTP invites all 
interested parties to present oral comments to the panel at the 
meeting. For planning purposes, individuals/groups wishing to give oral 
comment are asked to register early and provide appropriate contact 
information (name; affiliation; mailing address; phone; fax; e-mail; 
and sponsoring organization, if any). One time slot for an oral 
presentation will be allotted per organization. Speakers that register 
early for this meeting will be assigned time on a first-come, first-
served basis. Registration to speak at this meeting will also be 
accepted on-site. 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 text, the NTP asks that the speaker provide 15 
copies of the text at registration for distribution to the panel and to 
supplement the record of the meeting. Written statements can supplement 
or may expand on an oral presentation or can be submitted in lieu of an 
oral presentation.
    The NTP also invites the submission of written comment. Written 
comments should be sent to the address provided below and include 
contact information (name, affiliation, mailing address, phone, fax, e-
mail, and sponsoring organization, if any). Comments received by 
January 15, 2004, will be distributed to the panel, posted on the NTP 
RoC Web site prior to the meeting, and made available at the public 
meeting.

Registration for Meeting

    This meeting is open to the public and all interested parties are 
invited to attend. Persons needing special assistance in order to 
attend are asked to contact Ms. Anna Lee Sabella (contact information 
below) at least seven business days prior to the meeting. For planning 
purposes, persons are asked to register on-line or, if this is not 
possible, contact Ms. Anna Lee Sabella (Report on Carcinogens Group, 
NIEHS, P.O. Box 12233 MD EC-14, 79 T.W. Alexander Drive, Room 3123, 
Research Triangle Park, NC 27709; phone: (919) 541-4982; FAX: (919) 
541-0144; e-mail: [email protected]).
    Access to the electronic registration form is available from the 
NTP Web site (http://ntp-server.niehs.nih.gov, select NTP/RoC Public 
Meeting under ``What's New?''). Please complete the form and also 
indicate whether you want to request time for an oral presentation. On-
site registration will also be available and will begin the morning of 
January 27 at 8:30 am.

Access to the NIH Campus

    Any individual seeking access to the NIH campus to attend this 
meeting will need to be prepared to show two forms of identification 
(one must be a government-issued photo ID, e.g., driver's license, 
passport, green card, etc.) and, if asked, to provide pertinent 
information about this meeting (e.g., a copy of the meeting 
announcement, title of the meeting). Additional information about 
access to the NIH campus and parking is available from the NTP Web site 
(http://ntp-server.niehs.nih.gov,

[[Page 67694]]

select NTP/RoC Public Meeting under ``What's New?'').

    Dated: November 20, 2003.
Kenneth Olden,
Director, NTP.

Report on Carcinogens

Proposed Listing/Delisting Procedures

    Nominations for listing or delisting (removing) an agent, 
substance, mixture, or exposure circumstance in the RoC should be 
submitted to the NTP \1\ (footnotes are defined). 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.) that support the nomination should be 
provided or referenced when possible.
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    \1\ National Toxicology Program, Report on Carcinogens, P.O. Box 
12233, 79 T.W. Alexander Drive, Bldg. 4401, Room 3118, MD EC-14, 
Research Triangle Park, NC 27709; contact information: Dr. C. W. 
Jameson, phone (919) 541-4096, fax: (191) 541-0144, e-mail: 
[email protected]
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    A nomination for listing or delisting in the RoC is evaluated 
initially by the NIEHS/NTP RoC nomination review committee, composed of 
scientists from the NIEHS/NTP staff, to determine if the information 
available for a nomination indicates the criteria for listing can be 
applied and warrants formal consideration by the NTP. This committee is 
provided with the information submitted with each nomination and any 
relevant supplemental materials identified by RoC staff. The committee 
reviews the information provided for each nomination and makes a 
recommendation for either continuing with the formal review for listing 
or delisting or not pursuing the nomination at this time. The rationale 
for dropping a nomination would be the lack of sufficient information 
for applying the listing criteria or, in the case of nominations for 
delisting, the absence of significant new information published since 
the original listing. The recommendations of this committee are 
submitted to the Director, NTP for approval. Those nominations not 
accepted for review will be returned to the original nominator who is 
invited to resubmit the nomination with additional justification, which 
may include new data, exposure information, etc. The NTP Executive 
Committee \2\ and the NTP Board of Scientific Counselors are informed 
of all nominations not accepted for review for listing or delisting in 
the RoC.
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    \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 
Environmental Health of the Centers for Disease Control and 
Prevention (NCEH/CDC), National Institute for Occupational Safety 
and Health/CDC (NIOSH/CDC), Occupational Safety and Health 
Administration (OSHA), National Cancer Institute of the National 
Institutes of Health (NCI/NIH), and National Institute of 
Environmental Health Sciences/NIH(NIEHS/NIH)
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    The NTP announces its intent to review and solicits public comments 
on all nominations accepted for review through announcements in the 
Federal Register and NTP publications. The NTP will initiate an 
independent search and review of the literature and prepare a 
background document for each nomination under consideration. The 
comments received in response to the public announcement are used to 
help identify issues that should be addressed in the background 
documents. The background documents are prepared with the assistance of 
an expert consultant(s) who have expertise and/or knowledge for the 
specific nomination. Background documents are 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 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. Genotoxicity
    Information 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.
    The final draft of the background document for each nomination will 
be reviewed by the NIEHS/NTP RoC Review Committee (RG1) that is 
composed of senior scientists from the NIEHS/NTP staff. The RG1 is 
asked to review the background document for content and determine if it 
is adequate for use in reviewing the nomination and applying the 
criteria for listing in the RoC. Upon determination of adequacy, the 
background document is considered the final document of record and is 
placed on the NTP RoC Web site. A notice is then published on the NTP 
list-server and the NTP Web site announcing the availability of the 
background document for a nomination. Notification of the availability 
of background documents by mail can also be requested by contacting the 
NTP.\3\ The formal review of a nomination will not begin for at least 
45 day after the announcement of the availability of the background 
document for that nomination. All comments received within this time 
period will be distributed to the RoC review committees and also become 
part of the public record.
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    \3\ Contact information provided in footnote 1.
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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 conducts a formal review of nominations for listing in or 
delisting from the RoC. The RG1 reviews the background document for 
each nomination and all public comments received in response to the 
Federal Register announcement of the intent to

[[Page 67695]]

review a nomination and any comments received on the background 
document. The RG1 conducts a scientific review of the nomination 
applying the criteria and provides comments and makes its 
recommendations to the Director, NTP for listing or delisting it in the 
RoC.

NTP Executive Committee's Interagency Working Group for the RoC (RG2)

    The RG2, a federal government interagency scientific review group, 
also conducts a scientific 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 
the Federal Register announcement of the intent to review a nomination 
and any comments received on the background document. Upon completion 
of its review, the RG2 provides comments and makes its recommendations 
to the Director, NTP 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 public meeting, a reminder of 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. The RoC Subcommittee reviews the original 
nomination and all public comments received in response to the Federal 
Register notices including the announcement of the intent to review a 
nomination and the announcement of the public meeting, any comments 
received on the background documents, and comments received at the 
public 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 in the Federal Register and NTP 
publications the nominations and the review groups' recommendations for 
each (to list, to delist, or not to list in the RoC), and solicits 
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 in response to all Federal Register 
announcements and the background documents are presented to the NTP 
Executive Committee for review and comment. The NTP Executive Committee 
reviews the information on the nominations and provides the Director, 
NTP its recommendations 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 
recommendation 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

    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.

Report on Carcinogens

Criteria for Listing

Agents, Substances, Mixtures or Exposure Circumstances
Known To Be Human Carcinogen:
    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.
Reasonably Anticipated To Be Human Carcinogen:
    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 
known to be a human carcinogen or reasonably anticipated to be a 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.

Clarification of Criteria

    Some questions have arisen regarding information from studies 
involving humans and how this is applied to the listing of a substance 
determined to be a ``known human carcinogen''. The ``known human 
carcinogen'' category

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requires evidence from studies of humans. This can include traditional 
cancer epidemiology studies, data from clinical studies, and/or data 
derived from the study of tissues from humans exposed to the substance 
in question and useful for evaluating whether a relevant cancer 
mechanism is operating in people.
    There have also been some misunderstandings regarding the 
application of the final paragraph of the criteria which begins, 
``Conclusions regarding carcinogenicity in humans or experimental 
animals* * *'' Since these criteria were first published on September 
26, 1996 (61 FR 50499-50500), the paragraph has applied to both the 
``known to be human carcinogen'' and the ``reasonably anticipated to be 
human carcinogen'' categories and will continue to apply (64 FR 19188, 
April 19, 1999).
[FR Doc. 03-30122 Filed 12-2-03; 8:45 am]
BILLING CODE 4140-01-P