[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]]

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Part V





Department of Health and Human Services





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Public Health Service



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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