[Federal Register Volume 60, Number 110 (Thursday, June 8, 1995)]
[Notices]
[Pages 30434-30436]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-13874]
[[Page 30433]]
_______________________________________________________________________
Part V
Department of Health and Human Services
_______________________________________________________________________
Public Health Service
_______________________________________________________________________
National Toxicology Program (NTP) Proposed Revised Criteria for Listing
Substances in the Biennial Report on Carcinogens (BRC) and Notice of
Meeting of the NTP Board of Scientific Counselors
Federal Register / Vol. 60, No. 110 / Thursday, June 8, 1995 /
Notices
[[Page 30434]]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
National Toxicology Program (NTP) Proposed Revised Criteria for
Listing Substances in the Biennial Report on Carcinogens (BRC) and
Notice of Meeting of the NTP Board of Scientific Counselors
Background
A public meeting of the NTP Board of Scientific Counselors' ad hoc
Working Group to Review the Criteria for Listing Substances in the
Biennial Report on Carcinogens (BRC) was held on April 24 and 25, 1995,
at the Washington Hilton and Towers Hotel, 1919 Connecticut Avenue NW.,
Washington DC. The purpose of the meeting was to receive public
comments on the current criteria for listing substances in the BRC, and
to review and make recommendations on these criteria. The issues
addressed by this ad hoc group were: (1) The adequacy of existing
criteria for listing substances in future Reports; and (2) the
incorporation of mechanistic data as part of the criteria for listing
substances in future Reports which may include the consideration of
sensitive sub-populations as well as procedures to upgrade or downgrade
the evaluation of the results of animal bioassay or epidemiology
studies. A background and discussion document prepared by the NTP for
use by the ad hoc working group and also for review and comment by the
public, is available upon request. Copies of this document can be
obtained by contacting the NTP Liaison Office at NIEHS, P.O. Box 12233,
Research Triangle Park, NC 27709, or by FAX to (919) 541-0295.
This meeting was the first step in the review of the criteria and
was open to the public. The meeting began with a plenary session which
provided background on the BRC and a public comment session. The
working group then broke into three breakout groups, with each breakout
group addressing the same above listed issues. The final session of the
meeting was a plenary session at which time each breakout group
reported on their deliberations. The chairperson, rapporteur, and
facilitator of the three breakout groups completed draft reports of
their group's discussions and recommendations and submitted it to the
Chairperson of the ad hoc working group. The Chairperson, working with
NIEHS/NTP staff, completed a draft summary report of the criteria
review meeting which subsequently was sent to all ad hoc working group
members for editing and corrections. A copy of the revised summary
report is printed below. Also printed below are the current and
proposed revised criteria developed by the NIEHS/NTP based on the input
of the NTP Board of Scientific Counselors' ad hoc working group.
Action-Request for Public Input on the Proposed Revised Criteria
The NTP seeks comments and views on the proposed revised criteria
which follows. Public input concerning the proposed revised criteria
for listing a substance in the BRC is important to the review process
and is encouraged. A further opportunity for comment will be provided
during a meeting of the NTP Board of Scientific Counselors in the NIEHS
Conference Center, Building 101, South Campus, National Institute of
Environmental Health Sciences, 111 Alexander Drive, Research Triangle
Park, North Carolina, on June 29 , 1995. The primary agenda topic for
this meeting concerns the summary report and recommendations of the ad
hoc working group of the NTP Board from their review of the criteria
for listing substances in the BRC on April 24 and 25, 1995. This
meeting is open to the public, and public input concerning the criteria
for listing a substance in the Biennial Report on Carcinogens is
encouraged. Formal oral comments during the NTP Board meeting will be
limited to five minutes to permit maximum participation. Written
comments accompanying oral statements are encouraged. To assure
consideration by the Board at this meeting, written comments must be
submitted to Dr. Larry G. Hart, Executive Secretary for the NTP Board
of Scientific Counselors and received by June 23, 1995. Registration to
attend is not required; however, to ensure adequate seating, we ask
that those planning to attend let us know. To register, submit written
comments or announce intention to make oral comments on the criteria
review report, receive information on the agenda, or be put on the
mailing list for summary minutes subsequent to the meeting, please
contact: Dr. L. G. Hart, P.O. Box 12233, Research Triangle Park, NC
27709; telephone: (919) 541-3971; FAX: (919) 541-0719.
Dated: May 30, 1995.
Kenneth Olden,
Director, National Toxicology Program.
Attachments
Summary Report of the Meeting of the National Toxicology Program's
Board of Scientific Counselors' Ad Hoc Working Group To Review the
Criteria for Listing Substances in the Biennial Report on Carcinogens,
Washington Hilton and Towers Hotel, Washington, D.C., April 24 and 25,
1995
Background
The Biennial Report on Carcinogens is prepared in response to
Section 301(b)(4) of the Public Health Service Act which stipulates
that the Secretary of the Department of Health and Human Services
shall publish a report which contains a list of all substances (i)
which either are known to be human carcinogens or may reasonably be
anticipated to be human carcinogens; and (ii) to which a significant
number of persons residing in the United States are exposed. This
responsibility has been delegated by the Secretary to the Director,
National Toxicology Program (NTP). Dr. Ken Olden, Director of the
National Institute of Environmental Health Sciences (NIEHS) and the
National Toxicology Program, has initiated a review of the BRC to
broaden input to its preparation, broaden the scope of scientific
review associated with the Report, and provide review of the
criteria used for inclusion of substances in the BRC.
An ad hoc working group of the NTP Board of Scientific
Counselors was established to receive public comments on the
existing criteria and review and make recommendations on the
criteria for listing substances in the BRC. This ad hoc working
group had a balance of expertise and views and included
representatives from Academia; Industry; Labor; Federal, State and
Local Agencies; and Private Organizations. The working group
reviewed the criteria in an open, public meeting in Washington, D.C.
on April 24 & 25, 1995.
Meeting Summary
The ad hoc working group was chaired by NTP Board of Scientific
Counselors member Dr. Arnold Brown of the University of Wisconsin.
The working group was divided into three breakout groups to allow
for a more in depth discussion of the criteria and the public
comments received. Each of the breakout groups were asked to address
the following issues in their review of the criteria:
(a) The adequacy of existing criteria for listing substances in
future Reports; and
(b) The incorporation of mechanistic data as part of the
criteria for listing substances in future Reports that may include
the consideration of sensitive sub-populations as well as procedures
to upgrade or downgrade the evaluation of the results of animal
bioassay or epidemiology studies.
Plenary Session I was chaired by Dr. George Lucier, Director,
Environmental Toxicology Program, NIEHS/NTP and allowed for opening
and background presentations by Dr. Kenneth Olden, Director, NIEHS
and NTP, Dr. C. W. Jameson, NIEHS/NTP, and Dr. Marilyn Wind, CPSC
(NTP Executive Committee BRC Working Group representative). Dr.
Lucier then gave the charge to the ad hoc working group to
[[Page 30435]] address the two issues outlined above in their review
of the criteria and identify areas of consensus, areas of debate,
and the knowledge gaps that create the debate. Dr. Lucier then
turned the meeting over to Dr. Brown.
Plenary Session II was devoted to the presentation of public
comments concerning the BRC criteria. Written comments had been
received from the following individuals/organizations and
distributed to the ad hoc Working Group prior to the meeting:
North American Insulation Manufacturers Association
Chlorobenzene Producers Association
Dr. Stephen DeVito, US EPA
Dr. E. E. McConnell
Public comments were made during Plenary Session II by the
following individuals:
Dr. Charles Axten--NAIMA
Dr. Nathan Karch--Karch & Associates
Dr. Matthew Bogdanffy--Haskell Laboratory
Dr. James Sherman--Chlorobenzene Producers Association
Dr. Myra Karstadt--Center for Science in the Public Interest
Dr. Frank Mirer--United Auto Workers
Dr. E. E. McConnell--Private Consultant
Comments made during the public comment period ranged from
recommending retention of the current criteria with no change, to
revising the existing criteria to require the incorporation of
available mechanistic data. (A copy of the written public statements
provided by the above listed individuals is available upon written
request to the NTP Liaison Office, NIEHS, P.O. Box 12233, MD A3-01,
Research Triangle Park, NC 27709-2233). Following the public comment
session, Dr. Brown directed that each breakout group was to meet
individually and, based on the charge given to the ad hoc Working
Group by Dr. Lucier, address the BRC criteria.
Upon completion of the discussions of the three breakout groups,
the full ad hoc Working Group reconvened in the final Plenary III
session. Each breakout group made a report on their deliberations
and recommendations.
Each breakout group had addressed the two issues outlined in the
charge given by Dr. Lucier. Breakout group 1 stated in their report
that the existing criteria were found not to be adequate and
suggested revision of the criteria to include use of available
mechanistic data that is relevant for improving hazard
identification. The report from breakout group 2 stated there was
unanimity from their members that the criteria should be updated and
that mechanistic data should be utilized in the listing process.
Group 2 recommended significant revisions to the existing criteria
including the incorporation of additional listing categories.
Breakout group 3 report stated that their members were of the
general consensus that the current criteria are adequate for the
stated purpose of the BRC, however minor revisions and
clairifications to the existing criteria were considered to be
appropriate. In summary, it was the recommendation of breakout
groups 1 & 3 that the existing two categories of the current
criteria for listing substances in the BRC should remain with
revisions to category 2 to allow for all scientific evidence to be
considered. This will allow for the best scientific judgment to be
used in consideration of substances for listing in the BRC. Breakout
group 2 recommended a more significant expansion of the current
criteria which included the incorporation of additional listing
categories of ``presumptive evidence of carcinogenic activity'' and
``laboratory animal carcinogen presumed not to be a human
carcinogen''.
Based on the reports from the three breakout groups and the
ensuing discussions during the final plenary session of the entire
ad hoc Working Group, the NIEHS/NTP determined that, while there was
not complete agreement concerning the adequacy of the current
criteria for listing substances in the BRC, it was the general
consensus of the entire ad hoc Working Group that the existing
criteria should be revised and clarified. The recommended revisions
are to permit consideration of more mechanistic information in
listing substances in the BRC. As indicated in the three breakout
group reports, the area of debate was how extensive the
modifications should be. The discussions during Plenary Session III
indicated that the majority of the ad hoc Working Group members felt
the revised criteria should maintain the current 2 categories with
revisions to assure that all scientific evidence is considered to
allow for the best scientific judgment. It was also apparent from
these discussions that there was consensus that the BRC is a hazard
identification document and not to be used as a quantitative risk
assessment for the listed substances. It is based on these
considerations and recommendations that the NIEHS/NTP has proposed
revised criteria for listing substances in the BRC. These proposed
revisions are consistent with the discussion and recommendations of
the majority of the ad hoc Working Group and the current legislation
regarding the Biennial Report on Carcinogens. These proposed revised
criteria will be available to the public for review and comment and
presented to the NTP Board of Scientific Counselors at their June
29, 1995, meeting. The Board will review the report and
recommendations; receive public comment on the report; and develop
Board recommendations concerning the selection criteria. Further
review will include the PHS Environmental Health Policy Committee
and the NTP Executive Committee.
The ad hoc Working Group made several additional general
recommendations concerning the Biennial Report on Carcinogens. These
included recommending that a formal mechanism be established for the
re-evaluation of substances previously listed in the BRC to
determine if listing is still warranted. As a result of this
recommendation, the NTP will evaluate the current procedures for de-
listing a substance and, if necessary, revise it. It was also
recommended by the Working Group that the NTP should stimulate
discussion (e.g., workshops, discussion papers) on the use of
mechanistic data in hazard identification. The recent NTP workshop
on ``Mechanism-Based Toxicology in Cancer Risk Assessment:
Implications for Research, Regulation and Legislation'' held January
11-13, 1995, and the upcoming Workshop on Validation and Regulatory
Acceptance of Alternative Test Methods'' planned for October 30-
November 1, 1995 are examples of how this recommendation will be
acted upon. The NTP plans to continue these types of activities in
the future.
Current BRC Criteria
For the purpose of the BRC, the degrees of evidence are as
follows:
1. Known To Be Carcinogens
There is sufficient evidence of carcinogenicity from studies in
humans that indicates a causal relationship between the agent and
human cancer.
2. Reasonably Anticipated To Be Carcinogens
a. 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,
could not adequately be excluded, or
b. There is sufficient evidence of carcinogenicity from studies
in experimental animals that indicates that there is an increased
incidence of malignant tumors: (a) in multiple species or strains,
or (b) in multiple experiments (preferably with different routes of
administration or using different dose levels), or (c) to an unusual
degree with regard to incidence, site or type of tumor, or age at
onset. Additional evidence may be provided by data concerning dose-
response effects, as well as information on mutagenicity or chemical
structure.
Proposed Revised BRC Criteria
For the purpose of the BRC, the degrees of evidence are as
follows:
1. Known To Be Human Carcinogens
There is sufficient evidence of carcinogenicity from studies in
humans that indicates a causal relationship between the substance
and human cancer.
2. Reasonably Anticipated To Be Human Carcinogens
a. There is limited evidence of carcinogenicity from studies in
humans which indicate that causal interpretation is credible but
that alternative explanations such as chance, bias or confounding
could not adequately be excluded, or
b. There is sufficient evidence of carcinogenicity from studies
in experimental animals that indicates there is an increased
incidence of malignant and/or combined benign and malignant 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.
Conclusions regarding carcinogenicity in humans or experimental
animals should be based on scientific judgment. Consideration may be
given to relevant information on dose response, route of exposure,
chemical structure, sensitive sub populations, genetic effects or
other data relating to mechanism of action, and/or factors that may
be unique to a given substance. There may be substances for which
there is less than sufficient [[Page 30436]] evidence of
carcinogenicity in humans or laboratory animals but for which there
are compelling data indicating that the substance could reasonably
be anticipated to cause cancer in humans. Conversely, there may be
substances for which there is sufficient 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 reasonably be anticipated not to cause cancer in
humans.
National Toxicology Program Board of Scientific Counselors' Ad Hoc
Working Group for the Review of the Criteria for Listing Substances in
the Biennial Report on Carcinogens
List of Ad Hoc Working Group Members
Dr. Arnold Brown(Chairman)--University of Wisconsin Medical School
Dr. Bill Allaben--FDA/NCTR
Dr. Carl Barrett--NIEHS
Dr. Eula Bingham--Univ. of Cincinnati
Dr. John Dement--Duke University Medical Center
Dr. Norman Drinkwater--McArdle Laboratory , Univ. of Wisconsin
Dr. Kathleen Dixon--Univ. of Cincinnati, Dept. of Environ. Health
Dr. Gerard Egan--Exxon Biomedical Sciences Inc.
Dr. Clay Frederick--Rohm & Haas
Dr. Thomas Goldsworthy--Chemical Industry Institute of Toxicology
Dr. Bryan Hardin--NIOSH
Dr. David Longfellow--NCI
Dr. Judith MacGregor--Toxicology Consulting Services
Dr. Roger McClellan--Chemical Industry Institute of Toxicology
Dr. Karen Medville--Cornell University
Dr. James Melius--Center to Protect Workers' Rights
Dr. Beth Mileson--NC State Department of Health
Dr. Franklin Mirer--International Union, UAW
Dr. Rafael Moure--University of Massachusetts / Lowell
Dr. Gunter Oberdorster--Univ. of Rochester, Dept. Env. Medicine
Dr. Jean Parker--EPA/ORD
Dr. Janet Phoenix--Environmental Health Center, Washington, DC
Dr. Resha Putzrath--Georgetown Risk Group, Washington, DC
Dr. David Rall--Asst. Surgeon General, USPHS (Ret.)
Dr. Larry Roslinski--Ford Motor Company
Mr. Sheldon Samuels--Workplace Health Fund
Dr. Regina Santella--Columbia University, Dept. Environ. Sciences
Dr. Loretta Schuman--OSHA
Dr. Ellen Silbergeld--Environmental Defense Fund and the U of MD
Dr. Thomas Sinks--Nat'l Center for Env. Health, CDC
Dr. Thomas Slaga--Univ. of Texas, M.D. Anderson Cancer Center
Ms. Yee Wan--Stevens ATSDR
Dr. Donald Stevenson--Former Director of Toxicology, Shell Oil Co.
Dr. Lorenzo Tomatis--Former Director, IARC
Dr. Harri Vainio--Institute of Occupational Health, Finland
Dr. Vanessa Vu--EPA/OPPTS
Dr. Bailus Walker--Howard University
Dr. Cheryl Walker--Univ. of Texas, M.D. Anderson Cancer Center
Dr. Jerry Ward--National Cancer Institute
Dr. Marilyn Wind--CPSC
Dr. Sidney Wolfe--Public Citizens Group, Washington, DC
Dr. Hiroshi Yamasaki--IARC
Dr. Lauren Zeise--State of California EPA
[FR Doc. 95-13874 Filed 6-7-95; 8:45 am]
BILLING CODE 4140-01-P