[Federal Register Volume 61, Number 188 (Thursday, September 26, 1996)]
[Notices]
[Pages 50499-50500]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-24227]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service


The National Toxicology Program (NTP) Revised Criteria and 
Process for Listing Substances in the Biennial Report on Carcinogens

AGENCY: National Institute of Environmental Health Sciences, Public 
Health Service, HHS.

ACTION: Notice.

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SUMMARY: The Department of Health and Human Services is providing this 
notice of changes in the criteria for listing carcinogens in the 
Biennial Report on Carcinogens. The process for developing these 
changes was public and included participation of a broad base of 
interested parties. The revised criteria will be used to develop the 
eighth annual report.

FOR FURTHER INFORMATION CONTACT: Dr. C.W. Jameson, NIEHS/NTP, Biennial 
Report on Carcinogens, MD WC-05, P.O. Box 12233, Research Triangle 
Park, North Carolina 27709: fax 919 541-2242; internet 
J[email protected].

SUPPLEMENTARY INFORMATION:

Background

    Section 301(b)(4) of the Public Health Service Act, as amended, 
provides that the Secretary, Department of Health and Human Services 
(HHS), shall publish a report which contains a list of all substances 
(1) which either are known to be human carcinogens or may reasonably be 
anticipated to be human carcinogens; and (2) to which a significant 
number of persons residing in the United States (US) are exposed. The 
Biennial Report on Carcinogens is prepared by the National Toxicology 
Program (NTP).
    A review of the criteria used to list substances in the Report was 
initiated by the Director, NTP in late 1994. The process for the review 
was public and included participation of a broad base of interested 
persons including Academia, Industry, Labor, Federal, State and Local 
Agencies and Private Organizations. During 1995 the review included two 
open, public meetings by the NTP Board of Scientific Counselors and a 
number of internal reviews by HHS and the NTP Executive Committee 
agencies.
    At each step of the review there was concurrence with the following 
points: (1) the current criteria should be revised; (2) mechanistic 
information should be used as part of the listing criteria; (3) the 
categories (known to be human carcinogens and reasonably anticipated to 
be human carcinogens) should remain the same as described in the 
original legislation; and (4) there should be a formal mechanism which 
allows for the removal of substances from the BRC. Based on these 
recommendations, revised criteria and a new procedure for applying 
these criteria for inclusion or removal of substances in the BRC were 
prepared by the NTP with the assistance of NTP participating agencies.

Revised Criteria

    A point by point comparison of the former BRC criteria to the 
revised criteria follows. Sections that have been deleted from the 
former BRC criteria are in brackets []. The changes/additions in the 
revised criteria are highlighted by underlining.

Former BRC Criteria Known To Be Carcinogens

    There is sufficient evidence of carcinogenicity from studies in 
humans which indicates a causal relationship between the agent and 
human cancer.

Revised BRC Criteria 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.

Former BRC Criteria 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 which 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.]

Revised BRC Criteria 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, 
could not adequately be excluded, or
    There is sufficient evidence of carcinogenicity from studies in 
experimental animals which indicates that there is an increased 
incidence of malignant and/or combined benign and malignant tumors: (a) 
in multiple species or at multiple tissue sites, or (b) by multiple 
routes of exposure, or (c) 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,

[[Page 50500]]

substance or mixture belongs to a well defined, structurally-related 
class of substances whose members are listed in a previous Annual or 
Biennial 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.
    The following descriptive paragraph has been added to the criteria:
    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 
reasonably be anticipated not to cause cancer in humans.

Expanded Review Procedure

    External peer review is added to the review process through the 
establishment of a new, standing subcommittee of the NTP Board of 
Scientific Counselors. The BRC Subcommittee will meet twice a year, in 
public session, to review nominations for listing and /or delisting and 
to receive public comment.

Listing/Delisting Procedures

    Nominations of chemicals for listing or delisting will be solicited 
from government, industry, academia, Federal, State and local agencies, 
and the general public. However, nominations can be submitted to the 
National Toxicology Program at any time. Interested persons should send 
nominations which contain a justification for listing or delisting the 
agent, substance, or mixture in the BRC to the: National Toxicology 
Program, Biennial Report on Carcinogens, MD WC-05, P.O. Box 12233, 
Research Triangle Park, NC 27709. To the extent feasible, all 
appropriate background information and relevant data (e.g. scientific 
journal publications, NTP reports, IARC listings, exposure surveys, 
release inventories, etc.) that support the nomination should be 
provided or fully referenced to permit retrieval. Nominations will be 
reviewed as expeditiously as possible. A list of new petitions for 
listing or delisting will be routinely published in appropriate 
publications, including the Federal Register, trade journals, and the 
NTP Liaison Office mail-outs, soliciting public comment and input on 
the nominations.

    Dated: August 15, 1996.
Kenneth Olden,
Director National Institute of Environmental Health Sciences and the 
National Toxicology Program.
    Dated: September 12, 1996.
Donna E. Shalala,
Secretary.
[FR Doc. 96-24227 Filed 9-25-96; 8:45 am]
BILLING CODE 4140-01-P