[Federal Register Volume 64, Number 193 (Wednesday, October 6, 1999)]
[Notices]
[Pages 54343-54345]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-25940]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


Re-scheduled Meeting on Report on Carcinogens (RoC)

    National Toxicology Program Public Meeting to receive comment on 
the review procedures and listing criteria used in the preparation of 
the DHHS Report on Carcinogens (RoC); is re-scheduled from September 15 
to October 21 and 22, 1999, DoubleTree Hotel Rockville, 1750 Rockville 
Pike, Rockville, Maryland, beginning at 9 am.
    Due to weather conditions posed by Hurricane Floyd, the National 
Toxicology Program has re-scheduled a public meeting for the purpose of 
receiving comment on the procedures for reviewing nominations for 
listing in or delisting from the RoC and the current listing criteria 
used for evaluation of the nominations to the RoC. The purpose of this 
public meeting is to obtain input and to provide all interested parties 
an opportunity to express their views about the review process and/or 
the evaluation criteria and to comment on the views expressed by 
others. The purpose of the meeting is not to discuss the evidence for 
listing or delisting specific substances that are currently in the RoC 
or proposed for listing or delisting in the 9th or 10th RoC. However, 
it may be appropriate to use examples from the review of a specific 
substance to illustrate issues regarding the process.
    The meeting will begin at 9 am each day, with on-site registration 
at 8:30 am on October 21. The meeting will conclude at 5 pm on October 
21 and at 5 p.m. October 22 or the conclusion of the public comment and 
discussion, if sooner. Details regarding registration follow. 
Attendance at the meeting is limited only by the space available.

Background

    The DHHS Report on Carcinogens (RoC) is a public information 
document prepared for the US Congress by the National Toxicology 
Program in response to Section 301(b)(4) of the Public Health Service 
Act, as amended. The intent of the document is to provide 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 first edition of the report (then known as the Annual 
Report on Carcinogens) was published in 1980, and similar criteria and 
review processes were used to consider nominated substances for listing 
through preparation of the 7th edition published in 1994. In 1994 Dr. 
Ken Olden, Director of NTP and NIEHS established an ad hoc working 
group of the NTP Board of Scientific Counselors and charged them to 
review and make recommendations on two issues: the adequacy of the 
existing criteria and the incorporation of mechanistic data as part of 
the criteria for listing substances in future Reports. In addition Dr. 
Olden directed that the process used to review nominations for listing 
in or delisting from the Report be revised to allow more public input 
throughout the process and to add external review to broaden the scope 
of scientific review. As a consequence, in 1994 and 1995 the criteria 
were examined by a panel whose membership included academia, industry, 
labor, public/environmental organizations, state and local health 
departments and government who met in public session in public 
meetings. Recommendations were made for revising the listing criteria 
and the nomination review process which were approved by the Secretary, 
HHS on September 13, 1996 [Federal Register: September 26, 1996, Volume 
61, Number 188, Page 50499-50500]. The substances newly included in the 
8th edition of the Report on Carcinogens (1998) and the nominations for 
listing in or delisting from the 9th edition were evaluated using these 
revised review process and criteria.

Public Review and Comment Encouraged

    NTP staff will briefly summarize the process and the listing 
criteria from approximately 9:00 am to 10 am. The remainder of the time 
will be devoted to public comments by all interested parties and 
discussion of issues raised. Dr. Bernard Goldstein, Director of the 
Environmental and Occupational Health Sciences Institute of Rutgers and 
the University of Medicine and Dentistry of New Jersey, will serve as 
chair and moderator for the day. Dr. Goldstein, with the assistance of 
NTP Board of Scientific Counselors members, will identify issues raised 
by speakers and lead discussion sessions on the issues throughout the 
meeting.
    The NTP welcomes the continued and meaningful input from all 
stakeholders in reviewing the RoC process and the listing criteria as 
we move forward to the 10th edition of the RoC. The experience and 
perspectives of all stakeholders are critical to ongoing evaluations of 
nominations to the RoC.
    Oral comments: Speakers will be registered and assigned time on a 
first-come, first-served basis. Fifty-two speakers were registered for 
the previously scheduled, September 15, meeting, and the order of these 
presentations will remain the same. The meeting has been extended for a 
second day to ensure time for discussion and dialogue and to 
accommodate any additional speakers. The time allotted for each 
presentation will be dependent upon the total number of individuals who 
register to speak; we anticipate that adding a second day to the 
meeting will permit 10 minutes for each presenter. Each speaker will be 
asked to identify their supporting organization (if any). When oral 
comments are read from printed copy, it is requested that 10 copies of 
the text be provided when registering at the meeting to be distributed 
to the Chair and NTP Board members and to supplement the record of the 
meeting.
    Written comments are welcome and can be sent to the address given 
below. All comments previously submitted for the September 15 meeting 
will be considered. Written comments must

[[Page 54344]]

include name, affiliation, mailing address, phone, fax, e-mail, and 
sponsoring organization (if any).

RoC Listing/Delisting Procedures and Listing Criteria

    Revised criteria were announced first in the Federal Register and 
other publications in 1996 [Federal Register: September 26, 1996, 
Volume 61, Number 188, Page 50499-50500] and clarified in the FR and 
other publications in April 1999 (FR Vol. 64, No. 63 pp 15983-15984 and 
Vol. 64, No. 74; pp 19188-19189). The procedures and criteria can be 
found on the NTP website located at www.ntp-server.niehs.nih.gov

Registration for Meeting

    Pre-registration to attend this meeting can be made by notifying 
Ms. Angie Wilson by mail at NIEHS, Building 101, Room A328, P.O. Box 
12233, Research Triangle Park NC 27709, by phone at (919) 541-3971, by 
FAX at (919) 541-0295, or by e-mail at [email protected]. Please 
indicate if you wish to make an oral presentation. Those pre-registered 
for the September 15 meeting are asked to re-confirm their 
participation for October 21-22. On site registration will be available 
the morning of October 21, 1999 from 8:30 am to 9:00 am. If possible, 
those wishing to speak should provide a written copy of their statement 
or talking points before the October 21 meeting, to assist the Chair 
and Board Members in identifying issues for discussion and to 
supplement the record of the meeting. Those registering on site are 
requested to bring 10 copies of their statement or talking points. 
Written statements should supplement and may expand on the oral 
presentation, or may be submitted in lieu of an oral presentation. When 
registering to comment, please provide your name, affiliation, mailing 
address, phone, fax, e-mail, and sponsoring organization (if any).

Report on Carcinogens; Listing/Delisting Procedures

    Petitions for listing or delisting an agent, substance, mixture, or 
exposure circumstance in the Report on Carcinogens (RoC) should be 
submitted to the National Toxicology Program (NTP).\1\ Petitions 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.) which support a petition should be provided 
or referenced.
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    \1\ National Toxicology Program, Report on Carcinogens, P.O. Box 
12233, 79 Alexander Drive, Bldg. 4401, Room 3127, MD-EC-14, Research 
Triangle Park, NC 27709
    For information contact: Dr. C.W. Jameson, phone: (919) 541-
4096, fax: (919) 541-2242, email:[email protected]
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    An agent, substance, mixture, or exposure circumstance petitioned 
for listing or delisting will be announced in the Federal Register, 
trade journals, and NTP publications to solicit public comment. The 
original petition and all comments received will be evaluated by a 
National Institute of Environmental Health Sciences (NIEHS/NTP) Report 
on Carcinogens Review Committee (RG1), composed of scientists from the 
NIEHS/NTP, to determine if the information provided is sufficient to 
merit further consideration. If it is determined the petition warrants 
formal consideration, the NTP may initiate an independent search of the 
literature and prepare a draft review document for the substance under 
consideration. Draft documents will be prepared according to the 
following general format:

1.0  Introduction
    1.1  Chemical Information--synonyms, trade names, CAS #'s, 
molecular formula, molecular structure, etc.
    1.2  Physical-Chemical Properties
    1.3 Identification of Structural Analogs
    2.0  Exposure Assessment
    2.1  Production
    2.2  Use
     2.3  Environmental Exposure--environmental occurrence, 
environmental release, drinking water and food content, consumer 
products, occupational exposures, biomarkers of exposure
    2.4  Regulations--Occupational Exposure Limits (standards and 
criteria), ``other'' standards and criteria
3.0  Human Studies
    3.1  Epidemiology Studies--occupational studies, clinical trials, 
consumer exposure, other ``non-occupational'' exposures
    3.2  Laboratory Studies--controlled exposures
    3.3  Poisonings--case reports, accidents, symptoms and clinical 
signs
4.0  Animal Carcinogenicity Studies--subdivided by species
5.0  Genotoxicity
6.0  Mechanistic and Other Relevant Studies

Data used in the preparation of Sections 3 through 6 of the draft 
document must come from publicly available, peer reviewed sources.
    If it is determined that the petition contains insufficient 
information to warrant consideration by the NTP, it will be returned to 
the original petitioner who will be invited to resubmit the petition 
with additional justification, which may include new data, exposure 
information, etc. A notice, stating the action taken for a petitioned 
substance found to contain insufficient justification for 
consideration, will be published in the Federal Register, trade 
journals, and NTP publications, and included in subsequent editions of 
the RoC with the reason(s) why it was not considered further. This 
decision will also be forwarded to the NTP Executive Committee and 
Board of Scientific Counselors.

Formal Review Steps

    The following describes the review process for petitions that are 
considered by the NTP for listing in or delisting from the Report on 
Carcinogens.

NIEHS/NTP Review Committee for the Report on Carcinogens (RG1)

    The original petition and all public comments received in response 
to a petition will be reviewed by RG1. Assignment of a primary and 
secondary reviewer will be made upon receipt of a petition. Reviewers 
will lead discussions concerning the adequacy of the petition. If the 
petition warrants formal consideration, a search of pertinent databases 
will be performed and available citations will be reviewed by the 
primary reviewer. The primary reviewer will identify the relevant 
articles. After consultation with the secondary reviewer, the 
identified literature will be obtained and a draft summary of all 
available information from the original petition and the literature 
search will be prepared. The primary and secondary reviewers will 
examine the petition, the literature citations, and the draft document 
for completeness and adequacy. The draft document will be revised if 
necessary and presented by the primary reviewer to the RG1. Public 
comments received in response to announcements of petitions will also 
be considered. The RG1 will make a formal recommendation for those 
petitions determined to contain sufficient information for listing or 
delisting in the RoC. The petition then continues through the review 
process.
    Petitions reviewed by RG1 for which sufficient information could 
not be obtained will not proceed further. The other RoC review groups, 
as well as the

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NTP Executive Committee, will be informed of this action. The original 
petitioner will be notified of the RG1 action and invited to resubmit 
the petition with additional justification. All petitioned agents, 
substances, or mixtures reviewed by RG1 but not selected for listing or 
delisting will be 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 Report on 
Carcinogens (RG2)

    The second review phase of petitions will be done by the NTP 
Executive Committee's Interagency Working Group for the Report on 
Carcinogens (RG2). RG2 is a Governmental interagency group that 
assesses whether relevant information on the petitioned agent, 
substance, or mixture is available and sufficient for listing in or 
delisting from the RoC. A reviewer for each petition will be assigned 
from the RG2 who will be responsible for reviewing the draft document 
and for leading the Working Group's discussion of the petition. Public 
comments received in response to announcements of petitions will also 
be considered by RG2 during the review. Upon completion of its review, 
RG2 will provide comments and recommendations for any changes and/or 
additions to the draft document and also make its recommendation for 
listing or delisting. The petition then continues through the review 
process.

Board of Scientific Counselors RoC Subcommittee (External Peer Review)

    The third review phase for petitions will be performed by a 
subcommittee of the NTP Board of Scientific Counselors. This 
subcommittee serves as another independent peer review group that 
assesses whether the relevant information available is sufficient for 
listing in or delisting. The NTP Board RoC Subcommittee will review 
petitions in a public meeting. Prior to public review, a notice will be 
published in the Federal Register, trade journals, and NTP 
publications, soliciting public comment. The notice will also invite 
interested groups or individuals to submit written comments and/or to 
address the NTP Board RoC Subcommittee during the review meeting. 
Reviewers for each petition will be assigned from the NTP Board RoC 
Subcommittee who will be responsible for reviewing the draft document 
and leading the subcommittee's discussion of the petition. Upon 
completion of its review, NTP Board RoC Subcommittee will provide 
comments and recommendations for any changes and/or additions to the 
draft document and also make its formal recommendation for listing or 
delisting the petitioned agent, substance, or mixture.
    Upon completion of the reviews by RG1, RG2, and NTP Board RoC 
Subcommittee, those petitioned agents, substances, mixtures, or 
exposure circumstance which are recommended for listing in or delisting 
from the RoC, will be published in the Federal Register, trade 
journals, and NTP publications, and public comment and input on the 
recommendations will be solicited.

NTP Executive Committee

    The independent recommendations of RG1, RG2, and NTP Board RoC 
Subcommittee and all public comment will be presented to the NTP 
Executive Committee \2\ for review and comment.
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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 
Toxicological Research (NCTR), National Institute for Occupational 
Safety and Health (NIOSH), Occupational Safety and Health 
Administration (OSHA), Department of Health and Human Services 
(DHHS), National Institutes of Health (NIH), National Cancer 
Institute (NCI), National Library of Medicine (NLM), and National 
Institute of Environmental Health Sciences/NTP (NIEHS/NTP).
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NTP Director

    The Director, NTP receives the four independent recommendations 
from RG1, RG2, NTP Board RoC Subcommittee, and the NTP Executive 
Committee and makes the final decision regarding the proposed listing 
and/or delisting and submits the RoC to the Office of the Secretary, 
DHHS. Upon review and approval by the Secretary, DHHS and submission to 
Congress, a notice of the RoC publication, indicating all newly listed 
or delisted agents, substances, mixtures, or exposure circumstance will 
be published in the Federal Register, trade journals, and NTP 
publications.

Report on Carcinogens; Criteria for Listing Agents, Substances or 
Mixtures

1. Known To Be Human Carcinogens

    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.

2. Reasonably Anticipated To Be Human Carcinogens

    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 a 
known to be human carcinogen, or reasonably anticipated to be 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.

    Dated: September 29, 1999.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 99-25940 Filed 10-5-99; 8:45 am]
BILLING CODE 4140-01-P