[Federal Register Volume 66, Number 142 (Tuesday, July 24, 2001)]
[Notices]
[Pages 38430-38432]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 01-18391]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program; Call for Public Comments on 16 
Substances, Mixtures and Exposure Circumstances Proposed for Listing in 
the Report on Carcinogens, Eleventh Edition

Background

    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: [email protected].

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

[[Page 38431]]

information 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.

    Dated: July 12, 2001.
Kenneth Olden,
Director, National Toxicology Program.

   Summary for Agents, Substances, Mixtures or Exposure Circumstances to be Reviewed in 2001-2002 for Possible
                             Listing in the Report on Carcinogens, Eleventh Edition
----------------------------------------------------------------------------------------------------------------
 Nomination to be reviewed/CAS No.   Primary uses or exposures       Nominated by         Basis for nomination
----------------------------------------------------------------------------------------------------------------
1-Amino-2,4-dibromoanthraquinone    1-Amino-2,4-                NIEHS \1\............  Results of NTP Bioassay
 (81-49-2).                          dibromoanthraquinone is                            (TR 383, 1996) that
                                     an anthraquinone-derived                           reported clear evidence
                                     vat dye that is used in                            of carcinogenicity at
                                     the textile industry.                              multiple tumor sites in
                                                                                        multiple species of
                                                                                        experimental animals.
2-Amino-3,4-dimethylimidazo[4,5-    MeIQ is a heterocyclic      NIEHS \1\............  IARC \2\ finding of
 f]quinoline (MeIQ) (77094-11-2).    amine that is formed                               sufficient evidence of
                                     during heating or cooking                          carcinogenicity in
                                     and is found in cooked                             experimental animals
                                     meat and fish.                                     (Vol. 56; 1993).
Cobalt Sulfate (10026-24-1).......  Cobalt sulfate is used in   NIEHS \1\............  Results of NTP Bioassay
                                     electroplating and                                 (TR 471, 998) which
                                     electrochemical                                    reported clear evidence
                                     industries. It is also                             of carcinogenic activity
                                     used as a coloring agent                           in female F344/N rats
                                     for ceramics, a drying                             and male and female
                                     agent in inks, paints,                             B63F1 mice and some
                                     varnishes and linoleum,                            evidence of carcinogenic
                                     and has been added to                              activity in male F344/N
                                     animal feed as a mineral                           rats.
                                     supplement.
Diazoaminobenzene (DAAB) (136-35-   DAAB is used as an          NIEHS \1\............  Results of research
 6).                                 intermediate, complexing                           supported the by the NTP
                                     agent, polymer additive                            that demonstrated this
                                     and also to promote                                chemical is
                                     adhesion of natural                                quantitatively
                                     rubber to steel.                                   metabolized to benzene
                                                                                        (a known human
                                                                                        carcinogen).
Diethanolamine (DEA) (111-42-2)...  DEA is used in the          Dr. Franklin Mirer of  Results of NTP Bioassay
                                     preparation of              the United Auto        (TR 478, 1999) which
                                     surfactants used in         Workers.               reported clear evidence
                                     liquid laundry,                                    of carcinogenic activity
                                     dishwashing detergents,                            in male and female
                                     cosmetics, shampoos, and                           B6C3F1 mice.
                                     hair conditioners and in
                                     textile processing,
                                     industrial gas
                                     purification and as an
                                     anticorrosion agent.
Hepatitis B Virus (HBV)...........  HBV is a small DNA-         NIEHS \1\............  IARC \2\ finding of
                                     enveloped virus that is                            sufficient evidence of
                                     transmitted by                                     carcinogenicity in
                                     percutaneous or                                    humans (Vol. 59, 1994).
                                     permuscosal exposure to
                                     infectious blood or body
                                     fluids that contain blood.
Hepatitis C Virus (HCV)...........  HCV is an RNA-enveloped     NIEHS \1\............  IARC \2\ finding of
                                     virus that is transmitted                          sufficient evidence of
                                     mainly by percutaneous                             carcinogenicity in
                                     exposure to infectious                             humans (Vol. 59, 1994).
                                     blood and less
                                     efficiently by
                                     permuscosal exposure to
                                     infectious blood or body
                                     fluids that contain blood.
High Risk Human Papillomaviruses    HPVs are small, non-        NIEHS \1\............  IARC \2\ finding of
 (HPVs).                             enveloped viruses that                             sufficient evidence of
                                     infect the skin and oral                           carcinogenicity in
                                     and genital mucosa. HPV                            humans (Vol. 70, 1997).
                                     infections are common
                                     throughout the world.
X-Radiation and GAMMA ()-  The major exposures of      NIEHS \1\............  IARC \2\ finding of
 Radiation.                          concern for cancer from X-                         sufficient evidence of
                                      and -radiation                           carcinogenicity in
                                     are from the past use of                           humans (Vol. 75, 2000).
                                     atomic weapons and from
                                     medical uses of radiation.

[[Page 38432]]

 
Neutrons..........................  Exposure to neutrons        NIEHS \1\............  IARC \2\ finding of
                                     normally occurs from a                             sufficient evidence of
                                     mixed irradiation field                            carcinogenicity in
                                     in which neutrons are a                            humans (Vol. 75, 2000).
                                     minor component. The
                                     exceptions are exposure
                                     of patients to neutron
                                     radiotherapy beams and
                                     exposures of aircraft
                                     passengers and crew.
Occupational exposure to lead or    Major occupational          NIEHS \1\............  Recent published data
 lead compounds.                     exposures are in the lead                          that indicate an excess
                                     smelting and refining                              of cancers in workers
                                     industries, battery-                               exposed to lead and lead
                                     manufacturing plants,                              compounds.
                                     steel welding or cutting
                                     operations, construction,
                                     and firing ranges.
Naphthalene (91-20-3).............  Naphthalene is used as an   NIEHS \1\............  Results of NTP Bioassay
                                     intermediate in the                                (TR 500, 2000) that
                                     synthesis of many                                  reported clear evidence
                                     industrial chemicals, an                           of carcinogenicity in
                                     ingredient in some moth                            male & female rats and
                                     repellants and toilet                              some evidence in female
                                     bowl deodorants, as an                             mice.
                                     antiseptics for
                                     irrigating animal wounds
                                     and to control lice on
                                     livestock and poultry.
Nitrobenzene (98-95-3)............  Nitrobenzene is used        NIEHS \1\............  IARC \2\ finding
                                     mainly in the production                           sufficient of evidence
                                     of aniline, itself a                               of carcinogenicity in
                                     major chemical                                     experimental animals
                                     intermediate in the                                (Vol. 65, 1996).
                                     production of dyes.
Nitromethane (75-52-5)............  Nitromethane is used as an  NIEHS \1\............  Results of NTP Bioassay
                                     additive to many                                   (TR 461, 1997) that
                                     halogenated solvents and                           reported clear evidence
                                     aerosol propellants as a                           of carcinogenicity in
                                     stabilizer. It can also                            male & female mice and
                                     be used in specialized                             clear evidence in female
                                     fuels and in explosives.                           rats.
Phenylimidazopyridine [PhIP,        PhIP is a heterocyclic      Dr. Takashi Sugimura,  Nomination based on Dr.
 (105650-23-5)].                     amine that is formed        President Emeritus,    Sugimura's recent
                                     during heating or cooking   National Cancer        reviews of the
                                     and is found in cooked      Center of Japan.       carcinogenicity of
                                     meat and fish.                                     heterocyclic amines.
4,4'-Thiodianiline (139-65-1).....  4,4'-Thiodianiline has      NIEHS \1\............  IARC \2\ finding of
                                     been produced                                      sufficient evidence of
                                     commercially since the                             carcinogenicity in
                                     early 1940's as an                                 experimental animals
                                     intermediate of several                            (Suppl 7, 1987). and
                                     diazo dyes.                                        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]
BILLING CODE 4140-01-P