[Federal Register Volume 64, Number 134 (Wednesday, July 14, 1999)]
[Notices]
[Pages 37992-37995]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-17930]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
Nation Toxicology Program; Meeting
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); September 15, 1999, Ronald Reagan
Building, The International Trade Center, 1300 Pennsylvania Avenue,
NW., Horizon Room, Washington, DC, beginning at
9 a.m.
The National Toxicology Program announces a public meeting for the
purpose of 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 meeting will begin at 9 a.m. and will conclude at 5 p.m. or at
the conclusion of the public comment and discussion, if sooner. On-site
registration will begin at 8:30 a.m. 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 U.S. 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
[[Page 37993]]
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
A panel to include NTP staff and representatives of the NTP Board
of Scientific Counselors and the NTP Executive Committee will receive
comments and participate in the discussion. NTP staff will summarize
the process and the listing criteria. Presentations from the panel will
be tentatively from 9-10 a.m. The remainder of the time will be devoted
to public comment and discussion.
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
perspective of all stakeholdres are critical to ongoing evaluations of
nominations to the RoC.
Written comments are welcome and can be sent to the address given
below. Written comments must include name, affiliation, mailing
address, phone, fax, e-mail, and sponsoring organization (if any).
Comments received by September 15 will be considered for their
implications with respect to the reviews of nominations for the 10th
edition of the RoC and the December 16-17, 1999, public review.
Oral comments may be presented to the panel described above. Each
speaker will be asked to identify their supporting organization (if
any). The time allotted for each presentation will be largely dependent
upon the number of individuals who register to speak at this one day
meeting. Speakers will be registered and assigned time on a first-come,
first-served basis. Registration to speak at this meeting will be
accepted until the 9 a.m. start of the meeting. 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 copy, it is requested
that 10 copies of the text be provided when registering at the meeting
to be distributed to the panel members and to supplement the record of
the meeting.
RoC Listing/Delisting Procedures and Listing Criteria
The current procedures and listing criteria follow this
announcement. 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 also 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. On site registration
will be available the morning of September 15, 1999 from 8:30 am to
9:00 am. If possible, those wishing to speak should provide a written
copy of their statement before the September 15th meeting, to speak
should provide a written copy of their statement before the September
15th meeting, to permit copying for the panel members. Those
registering on site are requested to provide 10 copies of their
statement for distribution to the panel and to supplement the record of
the meeting. 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).
Dated: July 1, 1999.
Kenneth Olden,
Director, NTP and NIEHS.
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.
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
[[Page 37994]]
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 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 will 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.
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.
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]
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).
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.
[[Page 37995]]
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.
[FR Doc. 99-17930 Filed 7-13-99; 8:45 am]
BILLING CODE 4140-01-M