National Toxicology Program

[Federal Register: September 26, 1996 (Volume 61, Number 188)]
[Notices]
[Page 50499-50500]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service

 

THE NATIONAL TOXICOLOGY PROGRAM (NTP) REVISES CRITERIA AND PROCESS FOR LISTING SUBSTANCES IN THE BIENNIAL REPORT ON CARCNOGENS

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 intrested 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 Jameson@niehs.nih.gov.

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 in red.

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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, 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, Ph.D.
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