[Federal Register Volume 69, Number 97 (Wednesday, May 19, 2004)]
[Notices]
[Pages 28940-28944]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-11359]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program; Call for Public Comments on 21 
Substances, Mixtures and Exposure Circumstances Proposed for Listing in 
the Report on Carcinogens, Twelfth 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), 
Twelfth Edition that is scheduled for publication in 2006. 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 NTP 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.
    A nomination recommended for review in the RoC is evaluated 
initially by the NIEHS/NTP RoC nomination review committee, composed of 
scientists from the NIEHS/NTP staff, to determine if the information 
available for a nomination indicates the criteria for listing can be 
applied and warrants formal consideration by the NTP. The scientific 
review of a nomination 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 RoC 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

[[Page 28941]]

or exposure circumstances or for a change in a candidate's 
classification.
    The criteria used in the review process and a detailed description 
of the review procedures, including the steps in the current formal 
review process, can be obtained from the NTP Web site at http://ntp-server.niehs.nih.gov (see Report on Carcinogens) 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, e-mail: [email protected].

Public Comment Requested

    The following table identifies the 21 nominations that the NTP may 
consider for review in 2004 or 2005, as either a new listing in or 
changing the current listing in the Twelfth Report. These nominations 
are provided with their Chemical Abstracts Services (CAS) Registry 
numbers (where available) and pending review action. Additional 
nominations for the Twelfth 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 
21 nominations and asks for relevant 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 Twelfth Report on Carcinogens will 
be accepted for a period of 60 days from the publication date of this 
announcement in the Federal Register. Individuals submitting public 
comments are asked to include relevant contact information (name, 
affiliation (if any), address, telephone, fax, and e-mail). Comments or 
questions should be directed to Dr. C. W. Jameson at the address listed 
above.

Additional Nominations Encouraged

    The NTP solicits and encourages the broadest participation from 
interested individuals or parties in nominating agents, substances, or 
mixtures for review for the Twelfth and future RoCs. Nominations should 
contain a rationale for review. Appropriate background information and 
relevant data (e.g., journal articles, NTP Technical Reports, IARC 
listings, exposure surveys, release inventories, etc.), which support 
the review of 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 e-mail). 
Nominations should be sent to Dr. Jameson's attention at the address 
given above.

    Dated: May 10, 2004.
Kenneth Olden,
Director, National Toxicology Program.

   Summary for Agents, Substances, Mixtures or Exposure Circumstances To Be Reviewed in 2004-2005 for Possible
                               Listing the Report on Carcinogens, Twelfth Edition
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                                           Primary uses or
  Nomination to be reviewed/CAS No.           exposures               Nominated by         Basis for nomination
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Aristolochia-Related Remedies........  Several Aristolochia     NIEHS \1\..............  Herbal remedies
                                        Herbal species                                    containing the plant
                                        (notably A. contorta,                             genus Aristolochia:
                                        A. debilis, A. fangchi                            IARC \2\ finding of
                                        and A. manshuriensis)                             sufficient evidence of
                                        have been used in                                 carcinogenicity in
                                        traditional Chinese                               humans (Vol. 83,
                                        medicine as anti-                                 2002).
                                        rheumatics, as
                                        diuretics, in the
                                        treatment of edema and
                                        for other conditions
                                        such as hemorrhoids,
                                        coughs and asthma.
 Aristolochic Acid...................  Aristolochic acid, the   NIEHS \1\..............  Naturally occurring
                                        principle extract from                            mixtures of
                                        Aristolochia, is a                                aristolochic acids:
                                        mixture of                                        IARC \2\ finding of
                                        nitrophenanthrene                                 sufficient evidence of
                                        carboxylic acids.                                 carcinogenicity in
                                                                                          animals and limited
                                                                                          evidence in humans
                                                                                          (Vol. 83, 2002).
Asphalt fumes........................  Asphalt is a petroleum   John Schelp of NAACP-    Human epidemiological
                                        product used in paving   Durham Chapter.          studies have reported
                                        and roofing                                       an increased risk in
                                        operations. Asphalt                               lung cancer among
                                        fumes are a cloud of                              workers exposed to
                                        small particles                                   asphalt fumes and
                                        generated from the                                asphalt fumes caused
                                        gaseous state after                               skin tumors in
                                        volatilization of                                 experimental animals.
                                        asphalt aggregates.                               Additionally, known
                                                                                          human carcinogens
                                                                                          (PAHs) have been found
                                                                                          in asphalt fumes.
Atrazine (192-24-9)..................  Atrazine is an           NIEHS \1\..............  IARC \2\ finding of
                                        herbicide used to                                 sufficient evidence of
                                        control grass and                                 carcinogenicity in
                                        broad-leaved weeds.                               animals (Vol. 73,
                                        Atrazine has been                                 1999).
                                        detected at levels
                                        that exceeded or
                                        approached the MCL for
                                        atrazine in 200
                                        community surface
                                        drinking water system.

[[Page 28942]]

 
Benzofuran (271-89-6)................  Benzofuran is produced   NIEHS \1\..............  Results of a NTP
                                        by isolation from coal-                           bioassay (TR 370,
                                        tar oils. Benzofuran                              1989) that reported
                                        is used in the                                    clear evidence of
                                        manufacture of                                    carcinogenicity in
                                        coumarone-indene                                  male and female mice
                                        resins, which harden                              and some evidence of
                                        when heated and are                               carcinogenicity in
                                        used to make floor                                female rats.
                                        titles and other
                                        products.
Captafol (2425-06-01)................  Captafol is a fungicide  NIEHS \1\..............  IARC \2\ finding of
                                        that has been widely                              sufficient evidence of
                                        used since 1961 for                               carcinogenicity in
                                        the control of fungal                             animals (Vol. 53,
                                        diseases in fruits,                               1991). IARC also noted
                                        vegetables and some                               that captafol is
                                        other plants. Use of                              positive in many
                                        captafol in the United                            genetic assays,
                                        States was banned in                              including the in-vivo
                                        1999.                                             assay for dominant
                                                                                          lethal mutation.
Cobalt/Tungsten-Carbide Hard Metal     Hard-metals are          NIEHS \1\..............  Recent human cancer
 Manufacturing.                         manufactured by a                                 studies on the hard
                                        process of powder                                 metal manufacturing
                                        metallurgy from                                   industry an
                                        tungsten and carbon                               association between
                                        (tungsten carbide),                               exposure to hard
                                        and small amounts of                              metals (cobalt
                                        other metallic                                    tungsten-carbide) and
                                        compounds using cobalt                            lung cancer.
                                        as a binder. Hard
                                        metals are used to
                                        make cutting and
                                        grinding tools, dies,
                                        and wear products for
                                        a broad spectrum of
                                        industries including
                                        oil and gas drilling,
                                        and mining.
Di (2-ethylhexyl) phthalate (DEHP)     DEHP is mainly used as   Jun Ki-Chul, President   Currently listed in the
 (117-81-7).                            a plasticizer in         of Aekyung               RoC as reasonably
                                        polyvinyl chloride       Petrochemical Co., LTD   anticipated to be a
                                        (PVC) resins for         of Seoul, Korea (for     human carcinogen.
                                        fabricating flexible     delisting).             IARC reclassification
                                        vinyl products. PVC                               as not classifiable as
                                        resins have been used                             to its carcinogenicity
                                        to manufacture toys,                              to humans (Group 3)
                                        dolls, vinyl                                      (Vol. 73, 2000). IARC
                                        upholstery,                                       stated that there is
                                        tablecloths and many                              sufficient evidence
                                        other products.                                   for the
                                                                                          carcinogenicity in
                                                                                          experimental animals;
                                                                                          however, the mechanism
                                                                                          for liver tumor
                                                                                          involves peroxisome
                                                                                          proliferation that is
                                                                                          not relevant to
                                                                                          humans.
Etoposide in combination with          Etoposide in             NIEHS \1\..............  IARC \2\ finding of
 cisplatin and bleomycin.               combination with                                  sufficient evidence of
                                        cisplatin and                                     carcinogenicity in
                                        bleomycin is used to                              humans (Vol 76, 2000).
                                        treat testicular germ
                                        cell cancers.
Etoposide (33419-42-0)...............  Etoposide is a DNA       NIEHS \1\..............  IARC \2\ finding of
                                        topoisomerase II                                  limited evidence of
                                        inhibitor used in                                 carcinogenicity in
                                        chemotherapy for non-                             humans (Vol. 76,
                                        Hodgkin's lymphoma,                               2000).
                                        small-cell lung
                                        cancer, testicular
                                        cancer, lymphomas and
                                        a variety of childhood
                                        malignancies.
Glass wool (respirable size): Two      The major uses of glass  North American           Glass wool (respirable
 nominations: (1) Insulation glass      wool are in thermal,     Insulation               size) is currently
 wool fibers (2) Special purposes       electrical, and          Manufacturers            listed in the RoC as
 glass fibers.                          acoustical insulation,   Association nominated    reasonably anticipated
                                        weatherproofing, and     glass wool (respirable   to be a human
                                        filtration media. In     size) for delisting.     carcinogen.
                                        1980, approximately     Special purpose glass    Insulation glass wool:
                                        80% of the glass wool    wool fibers: NIEHS \1\.  IARC \2\ finding of
                                        produced for                                      limited evidence of
                                        structural insulation                             carcinogenicity in
                                        was used in houses.                               animals and evaluation
                                        Special purpose fibers                            as not classifiable as
                                        are used for high-                                to its carcinogenicity
                                        efficiency air                                    to humans (Group 3)
                                        filtration media, and                             (Vol. 81, 2002).
                                        acid battery                                     Special-purpose glass
                                        separators.                                       fibers: IARC \2\
                                                                                          finding of sufficient
                                                                                          evidence of
                                                                                          carcinogenicity in
                                                                                          animals (Vol. 81,
                                                                                          2002).

[[Page 28943]]

 
Metalworking Fluids..................  Metal working fluids     NIEHS \1\..............  Recent human cancer
                                        are complex mixtures                              studies of metal
                                        that may contain                                  working fluid that
                                        mixtures of oil,                                  show an association
                                        emulsifiers, anti-weld                            between exposure to
                                        agents, corrosion                                 these materials and
                                        inhibitors, extreme                               cancer at several
                                        pressure additives,                               tissue sites.
                                        buffers biocides and
                                        other additives. They
                                        are used to cool and
                                        lubricate tools and
                                        working surfaces in a
                                        variety of industrial
                                        machining and grinding
                                        operations.
otho-Nirotoluine (88-72-2)...........  ortho-Nitrotoluene is    NIEHS \1\..............  Results of a NTP
                                        used to synthesize                                bioassay (TR 504,
                                        agricultural and                                  2002), which reported
                                        rubber chemicals, azo                             clear evidence of
                                        and sulfur dyes, and                              carcinogenicity in
                                        dyes for cotton, wool,                            rats and mice.
                                        silk, leather, and
                                        paper.
Oxazepam (604-75-1)..................  Oxazepam is a            NIEHS \1\..............  Results of a NTP
                                        benzodiazepine used                               bioassay (TR 443,
                                        extensively since the                             1993), which reported
                                        1960s for the                                     clear evidence of
                                        treatment of anxiety                              carcinogenicity in
                                        and insomnia and in                               male and female mice.
                                        the control of
                                        symptoms of alcohol
                                        withdrawal.
Riddelliine (232476-96-0)............  Riddelliine is found in  NIEHS \1\..............  Results of a NTP
                                        a class of plants                                 bioassay (TR 508,
                                        growing in western                                2003), which reported
                                        United States. Cattle,                            clear evidence of
                                        horses and sheep                                  carcinogenicity in
                                        ingest these toxic                                male and female rats
                                        plants. Residues have                             and mice.
                                        been found in, milk,
                                        and honey.
Styrene (100-42-5)...................  Styrene is used in the   Lorenzo Tomatis........  IARC \2\ finding of
                                        production of                                     limited evidence of
                                        polystyrene,                                      carcinogenicity in
                                        acrylonitrile-                                    animals and limited
                                        butadiene-styrene                                 evidence of
                                        resins, styrene-                                  carcinogenicity in
                                        butadiene rubbers and                             humans (Vol. 82,
                                        latexes, and                                      2002).
                                        unsaturated
                                        polystyrene resins.
Talc Two nominations (1) Cosmetic      Talc occurs in various   NIEHS \1\..............  The NTP deferred
 talc (2) Occupational exposure to      geological settings                               consideration of
 talc.                                  around the world.                                 listing talc
                                        Exposure to general                               (asbestiform and non-
                                        population occurs                                 asbestiform talc) in
                                        through use of                                    the 10th RoC because
                                        products such as                                  its 2000 review of
                                        cosmetics.                                        talc found confusion
                                        Occupational exposure                             in the scientific
                                        occurs during mining,                             literature over the
                                        milling and processing.                           mineral nature of
                                                                                          talc. Given the
                                                                                          confusion over
                                                                                          defining exposure to
                                                                                          talc based on
                                                                                          asbestiform fibers,
                                                                                          the NPT has decided
                                                                                          that the most
                                                                                          appropriate approach
                                                                                          would be to
                                                                                          characterize talc
                                                                                          exposure as cosmetic
                                                                                          talc and occupational
                                                                                          exposure to talc. The
                                                                                          basis for the review
                                                                                          of talc is as follows:
                                                                                         Cosmetic talc: Human
                                                                                          epidemiological
                                                                                          studies reporting an
                                                                                          increased risk of
                                                                                          ovarian cancer among
                                                                                          women using talc for
                                                                                          personal use.
                                                                                         Occupational exposure
                                                                                          to talc: Human
                                                                                          epidemiological
                                                                                          studies reporting an
                                                                                          increase risk of
                                                                                          cancer among workers
                                                                                          exposed to talc.
Teniposide (29767-20-2)..............  Teniposide is a DNA      NIEHS \1\..............  IARC \2\ finding of
                                        toposiomerase II                                  limited evidence of
                                        inhibitors used mainly                            carcinogenicity in
                                        in the treatment of                               humans (Vol. 76,
                                        adult childhood                                   2000).
                                        leukemia.

[[Page 28944]]

 
Vinyl Mono-Halides as a class........  Vinyl halides are used   NIEHS\1\...............  Vinyl Fluoride and
                                        in the production of                              Vinyl Bromide are
                                        polymers and                                      currently listed in
                                        copolymers. Vinyl                                 the RoC as reasonably
                                        bromide is mainly used                            anticipated to be a
                                        in polymers as a flame                            human carcinogen and
                                        retardant and in the                              Vinyl Chloride is
                                        production of                                     currently listed in
                                        monoacrylic fibers of                             the RoC as known to be
                                        carpet-backing                                    a human carcinogen in
                                        materials. Vinyl                                  the Report on
                                        Chloride is used to                               Carcinogens.
                                        produce polyvinyl                                Vinyl Mono-Halides:
                                        chloride and                                      Structural
                                        copolymers. Vinyl                                 similarities and
                                        Fluoride is used in                               common mechanisms of
                                        the production of                                 tumor formation.
                                        polyvinyl fluoride,
                                        which when laminated
                                        with aluminum, steel
                                        and other materials is
                                        used as a protective
                                        surface for the
                                        exteriors of
                                        residential and
                                        commercial buildings.
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\1\ The National Institute of Environmental Health Sciences (NIEHS).
\2\ International Agency for Research on Cancer (IARC).

[FR Doc. 04-11359 Filed 5-18-04; 8:45 am]
BILLING CODE 4140-01-P