[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
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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 wilson9@niehs.nih.gov. 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:jameson@niehs.nih.gov
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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
