The National Toxicology Program (NTP) announces its intent to review additional agents, substances, mixtures and exposure circumstances for possible listing in the Report on Carcinogens (RoC), Eleventh Edition that is scheduled for publication in 2004. This Report (previously known as the Annual Report on Carcinogens) is a Congressionally mandated listing of known human carcinogens and reasonably anticipated human carcinogens and its preparation is delegated to the National Toxicology Program by the Secretary, Department of Health and Human Services (DHHS). Section 301(b)(4) of the Public Health Service Act, as amended, provides that the Secretary, DHHS 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 law also states that the reports should provide available information on the nature of exposures, the estimated number of persons exposed and the extent to which the implementation of Federal regulations decreases the risk to public health from exposure to these chemicals.
The scientific review of the nominated agents, substances, mixtures or exposure circumstances involves three separate scientific reviews: Two Federal review groups and one non-government peer review body (a subcommittee of the NTP Board of Scientific Counselors) that meets in an open, public forum. Throughout the review process, multiple opportunities are provided for public input including comment at the public meeting of the NTP Board Subcommittee. In reviewing nominations for the RoC, all available data and public comments are considered in the application of the criteria for inclusion or removal of candidate agents, substances, mixtures or exposure circumstances or for a change in a candidate's classification. The criteria used in the review process are as follows:
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.
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 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.
A detailed description of the review procedures, including the steps in the formal review process, is available at http://ntp-server.niehs.nih.gov or can be obtained by contacting: Dr. C.W. Jameson, National Toxicology Program, Report on Carcinogens, 79 Alexander Drive, Building 4401, Room 3118, P.O. Box 12233, Research Triangle Park, NC 27709; phone: (919) 541-4096, fax: (919) 541-0144, email: firstname.lastname@example.org.
Public Comment Requested
The following table identifies the 16 nominations the NTP may consider for review in 2001 or 2002, as either a new listing in or changing the current listing from reasonably anticipated to be a human carcinogen to the known to be a human carcinogen category in the Eleventh Report. These nominations are provided with their Chemical Abstracts Services (CAS) Registry numbers (where available) and pending review action. Additional nominations for the Eleventh Report or modifications to the nominations in the attached table may be identified and would be announced in future Federal Register notices. The NTP solicits public input on these 16 nominations and asks for relevant Start Printed Page 38431information concerning their carcinogenesis, as well as current production data, use patterns, or human exposure information. The NTP also invites interested parties to identify any scientific issues related to the listing of a specific nomination in the RoC that they feel should be addressed during the reviews. Comments concerning these nominations for listing in or changing the current listing in the Eleventh Report on Carcinogens will be accepted through September 24, 2001. Individuals submitting public comments are asked to include relevant contact information (name, affiliation (if any), address, telephone, fax, and email). Comments or questions should be directed to Dr. C.W. Jameson at the address listed above.
Additional Nominations for Delisting or Listing Encouraged
The NTP solicits and encourages the broadest participation from interested individuals or parties in nominating agents, substances, or mixtures for listing in or delisting from the Eleventh and future RoCs. Nominations should contain a rationale for listing or delisting. Appropriate background information and relevant data (e.g. Journal articles, NTP Technical Reports, IARC listings, exposure surveys, release inventories, etc.), which support a nomination, should be provided or referenced when possible. Contact information for the nominator should also be included (name, affiliation (if any), address, telephone, fax, and email). Nominations should be sent to Dr. Jameson's attention at the address given above.Start Signature
Dated: July 12, 2001.
Director, National Toxicology Program.
|Nomination to be reviewed/CAS No.||Primary uses or exposures||Nominated by||Basis for nomination|
|1-Amino-2,4-dibromoanthraquinone (81-49-2)||1-Amino-2,4-dibromoanthraquinone is an anthraquinone-derived vat dye that is used in the textile industry||NIEHS 1||Results of NTP Bioassay (TR 383, 1996) that reported clear evidence of carcinogenicity at multiple tumor sites in multiple species of experimental animals.|
|2-Amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) (77094-11-2)||MeIQ is a heterocyclic amine that is formed during heating or cooking and is found in cooked meat and fish||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in experimental animals (Vol. 56; 1993).|
|Cobalt Sulfate (10026-24-1)||Cobalt sulfate is used in electroplating and electrochemical industries. It is also used as a coloring agent for ceramics, a drying agent in inks, paints, varnishes and linoleum, and has been added to animal feed as a mineral supplement||NIEHS 1||Results of NTP Bioassay (TR 471, 998) which reported clear evidence of carcinogenic activity in female F344/N rats and male and female B63F1 mice and some evidence of carcinogenic activity in male F344/N rats.|
|Diazoaminobenzene (DAAB) (136-35-6)||DAAB is used as an intermediate, complexing agent, polymer additive and also to promote adhesion of natural rubber to steel||NIEHS 1||Results of research supported the by the NTP that demonstrated this chemical is quantitatively metabolized to benzene (a known human carcinogen).|
|Diethanolamine (DEA) (111-42-2)||DEA is used in the preparation of surfactants used in liquid laundry, dishwashing detergents, cosmetics, shampoos, and hair conditioners and in textile processing, industrial gas purification and as an anticorrosion agent||Dr. Franklin Mirer of the United Auto Workers||Results of NTP Bioassay (TR 478, 1999) which reported clear evidence of carcinogenic activity in male and female B6C3F1 mice.|
|Hepatitis B Virus (HBV)||HBV is a small DNA-enveloped virus that is transmitted by percutaneous or permuscosal exposure to infectious blood or body fluids that contain blood||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol. 59, 1994).|
|Hepatitis C Virus (HCV)||HCV is an RNA-enveloped virus that is transmitted mainly by percutaneous exposure to infectious blood and less efficiently by permuscosal exposure to infectious blood or body fluids that contain blood||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol. 59, 1994).|
|High Risk Human Papillomaviruses (HPVs)||HPVs are small, non-enveloped viruses that infect the skin and oral and genital mucosa. HPV infections are common throughout the world||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol. 70, 1997).|
|X-Radiation and GAMMA (γ)-Radiation||The major exposures of concern for cancer from X- and γ-radiation are from the past use of atomic weapons and from medical uses of radiation||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol. 75, 2000).|
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|Neutrons||Exposure to neutrons normally occurs from a mixed irradiation field in which neutrons are a minor component. The exceptions are exposure of patients to neutron radiotherapy beams and exposures of aircraft passengers and crew||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in humans (Vol. 75, 2000).|
|Occupational exposure to lead or lead compounds||Major occupational exposures are in the lead smelting and refining industries, battery-manufacturing plants, steel welding or cutting operations, construction, and firing ranges||NIEHS 1||Recent published data that indicate an excess of cancers in workers exposed to lead and lead compounds.|
|Naphthalene (91-20-3)||Naphthalene is used as an intermediate in the synthesis of many industrial chemicals, an ingredient in some moth repellants and toilet bowl deodorants, as an antiseptics for irrigating animal wounds and to control lice on livestock and poultry||NIEHS 1||Results of NTP Bioassay (TR 500, 2000) that reported clear evidence of carcinogenicity in male & female rats and some evidence in female mice.|
|Nitrobenzene (98-95-3)||Nitrobenzene is used mainly in the production of aniline, itself a major chemical intermediate in the production of dyes||NIEHS 1||IARC 2 finding sufficient of evidence of carcinogenicity in experimental animals (Vol. 65, 1996).|
|Nitromethane (75-52-5)||Nitromethane is used as an additive to many halogenated solvents and aerosol propellants as a stabilizer. It can also be used in specialized fuels and in explosives||NIEHS 1||Results of NTP Bioassay (TR 461, 1997) that reported clear evidence of carcinogenicity in male & female mice and clear evidence in female rats.|
|Phenylimidazopyridine [PhIP, (105650-23-5)]||PhIP is a heterocyclic amine that is formed during heating or cooking and is found in cooked meat and fish||Dr. Takashi Sugimura, President Emeritus, National Cancer Center of Japan||Nomination based on Dr. Sugimura's recent reviews of the carcinogenicity of heterocyclic amines.|
|4,4′-Thiodianiline (139-65-1)||4,4′-Thiodianiline has been produced commercially since the early 1940's as an intermediate of several diazo dyes||NIEHS 1||IARC 2 finding of sufficient evidence of carcinogenicity in experimental animals (Suppl 7, 1987). and result of NTP Bioassay studies that demonstrated clear evidence of carcinogenicity in mice and rats (TR-047, 1978).|
|1 The National Institute of Environmental Health Sciences (NIEHS).|
|2 International Agency for Research on Cancer (IARC).|
[FR Doc. 01-18391 Filed 7-23-01; 8:45 am]
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