[Federal Register Volume 69, Number 205 (Monday, October 25, 2004)]
[Notices]
[Pages 62276-62279]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-23788]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program; Call for Additional Public Comments 
on 21 Substances, Mixtures and Exposure Circumstances Proposed for 
Review for Listing or Changing the Current Listing in the Report on 
Carcinogens, Twelfth Edition

Background

    The National Toxicology Program (NTP) initially announced its 
intent to review additional agents, substances, mixtures and exposure 
circumstances for possible listing or changing the current listing in 
the Report on Carcinogens (RoC), Twelfth Edition in a May 19, 2004 
Federal Register notice (69 FR 28940 (May 19, 2004)). Based on some of 
the comments received in response to this notice, the NTP is concerned 
that there might have been confusion about the procedures that will be 
used for review of nominations to the 12th RoC. A detailed description 
of the current review procedures, including the steps in the formal 
review process, is available on the Web at http://ntp-server.niehs.nih.gov (select on 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, PO 
Box 12233, Research Triangle Park, NC 27709; phone: (919) 541-4096, 
fax: (919) 541-0144, e-mail: [email protected].

Public Comment Requested

    Because of the possibility of confusion over the review procedures 
for the 12th RoC nominations, additional comments concerning the 
nominations for listing or changing the current listing in the 12th RoC 
will be accepted by the NTP for a period of 30 days from the 
publication date of this announcement in the Federal Register. The 
following table identifies the 21 nominations the NTP may consider for 
review in 2004 or 2005, as either a new listing in or changing the 
current listing in the 12th RoC. These nominations are provided with 
their Chemical Abstracts Services (CAS) Registry numbers (where 
available) and pending review action. Additional nominations for the 
12th RoC 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.
    Individuals who submitted comments in response to the May 19, 2004 
Federal Register (69 FR 28940 (May 19, 2004)) that initially announced 
the 12th RoC nominations need not re-submit their comments as they are 
already part of the public record. Individuals submitting new or 
additional 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 email). 
Nominations should be sent to Dr. Jameson's attention at the address 
given above.

    Dated: October 15, 2004.
Samuel Wilson,
Deputy Director, National Institute of Environmental Health Sciences.

[[Page 62277]]



   Summary for Agents, Substances, Mixtures or Exposure Circumstances To Be Reviewed in 2004-2005 for Possible
                               Listing the Report on Carcinogens, Twelfth Edition
----------------------------------------------------------------------------------------------------------------
   Nomination to be reviewed/CAS
              number                 Primary uses or exposures       Nominated by         Basis for nomination
----------------------------------------------------------------------------------------------------------------
Aristolochia-Related Herbal         Several Aristolochia        NIEHS \1\............  Herbal remedies
 Remedies.                           species (notably A.                                containing the plant
                                     contorta, A. debilis, A.                           genus Aristolochia: IARC
                                     fangchi and A.                                     \2\ finding evidence of
                                     manshuriensis) have been                           carcinogenicity in
                                     used in traditional                                humans (Vol. 83, 2002).
                                     Chinese medicine as anti-
                                     rheumatics, as
                                     diruretics, 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 aristolochic
                                     Aristolochia, is a                                 acids: IARC \2\ finding
                                     mixture of                                         of sufficient evidence
                                     nitrophenanthrene                                  of carcinogenicity in
                                     carboxylic acids.                                  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 an
                                     and roofing operations.                            increased risk in lung
                                     Asphalt fumes are a cloud                          cancer among workers
                                     of small particles                                 exposed to asphalt fumes
                                     generated from the                                 and asphalt fumes caused
                                     gaseous state after                                skin tumors in
                                     volatilization of asphalt                          experimental animals.
                                     aggregates.                                        Additionally, known
                                                                                        human carcinogens (PAHs)
                                                                                        have been found in
                                                                                        asphalt fumes.
Atrazine (192-24-9)...............  Atrazine is an herbicide    NIEHS \1\............  IARC \2\ finding of
                                     used to control grass and                          sufficient evidence of
                                     broad-leaved weeks.                                carcinogenicity in
                                     Atrazine has been                                  animals (Vol. 73, 1999).
                                     detected at levels that
                                     exceeded or approached
                                     the MCL for atrazine in
                                     200 community surface
                                     drinking water systems.
Benzofuran (271-89-6).............  Benzofuran is produced by   NIEHS \1\............  Results of a NTP bioassay
                                     isolation from coal-tar                            (TR 370, 1989), which
                                     oils. Benzofuran is used                           reported clear evidence
                                     in the manufacture of                              of carinogenicity in
                                     coumarone-indene resins,                           male and female mice and
                                     which harden when heated                           some evidence of
                                     and are used to make                               carcinogenicity in
                                     floor titles and other                             female rats.
                                     products.
Captafol (2425-06-01).............  Captafol is a fungicide     NIEHS \1\............  IARC \2\ finding of
                                     that has been widely used                          sufficient evidence of
                                     since 1961 for the                                 carcinogenicity in
                                     control of fungal                                  animals (Vol. 53, 1991).
                                     diseases in fruits,                                IARC also noted that
                                     vegetables and some other                          captafol is positive in
                                     plants. Use of captafol                            many genetic assays,
                                     in the United States was                           including the in-vivo
                                     banned in 1999.                                    assay for dominant
                                                                                        lethal mutation.
Cobalt/Tungsten-Carbide Hard Metal  Hard-metals are             NIEHS \1\............  Recent human cancer
 Manufacturing.                      manufactured by a process                          studies on the hard
                                     of powder metallurgy from                          metal manufacturing
                                     tungsten and carbon                                industry showing an
                                     (tungsten carbide), and                            association between
                                     small amounts of other                             exposure to hard metals
                                     metallic compounds using                           (cobalt tungsten-
                                     cobalt as a binder. Hard                           carbide) and lung
                                     metals are used to make                            cancer.
                                     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 a    Jun Ki-Chul,           Currently listed in the
 (117-81-7).                         plasticizer in polyvinyl    President of Aekyung   RoC as reasonably
                                     chloride (PVC) resins for   Petrochemical Co.,     anticipated to be a
                                     fabricating flexible        LTD of Seoul, Korea    human carcinogen.
                                     vinyl products. PVC         (for delisting).      IARC reclassification as
                                     resins have been used to                           not classifiable as to
                                     manufacture toys, dolls,                           its carcinogenicity to
                                     vinyl upholstery,                                  humans (Group 3) (Vol.
                                     tablecloths and many                               73, 2000). IARC stated
                                     other products.                                    that there was
                                                                                        sufficient evidence 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 combination    NIEHS \1\............  IARC \2\ finding of
 cisplatin and bleomycin.            with cisplating and                                sufficient evidence of
                                     bleomycin is used to                               carcinogenicity in
                                     treat testicular germ                              humans (Vol. 76, 2000).
                                     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, 2000).
                                     Hodgkin's lyumphoma,
                                     small-cell lung cancer,
                                     testicular cancer,
                                     lymphomas and a variety
                                     of childhood malignancies.

[[Page 62278]]

 
Glass wool (respirable size): Two   The major uses of glass     North American         Glass wool (respirable
 nominations:                        wool are in thermal,        Insulation             size) is currently
(1) Insulation glass wool fibers.    electrical, and             Manufacturers          listed in the RoC as
(2) Special purposes glass fibers.   acoustical insulation,      Association            reasonably anticipated
                                     weatherproofing, and        nominated glass wool   to be a human
                                     filtration media. In        (respirable size)      carcinogen.
                                     1980, approximately 80%     for delisting.        Insulation glass wool:
                                     of the glass wool          Special purpose glass   IARC \2\ finding of
                                     produced for structural     wool fibers: NIEHS     limited evidence of
                                     insulation was used in      \1\.                   carcinogenicity in
                                     houses. Special purpose                            animals and evaluation
                                     fibers are used for high-                          as not classifiable as
                                     efficiency air filtration                          to its carcinogenicity
                                     media, and acid battery                            to humans (Group 3)
                                     separators.                                        (Vol. 81, 2002).
                                                                                       Special-purpose glass
                                                                                        fibers: IARC \2\ finding
                                                                                        of sufficient evidence
                                                                                        of carcinogenicity in
                                                                                        animals (Vol. 81, 2002).
Metalworking Fluids...............  Metal working fluids are    NIEHS \1\............  Recent human cancer
                                     complex mixtures that may                          studies of metal working
                                     contain mixtures of oil,                           fluid that show an
                                     emulsifiers, anti-weld                             association between
                                     agents, corrosion                                  exposure to these
                                     inhibitors, extreme                                materials and cancer at
                                     pressure additives,                                several 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-Nitrotolume (88-72-2)........  ortho-Nitrotoluene is used  NIEHS \1\............  Results of a NTP bioassay
                                     to synthesize                                      (TR 504, 2002), which
                                     agricultural and rubber                            reported clear evidence
                                     chemicals, azo and sulfur                          of carcinogenicity in
                                     dyes, and dyes for                                 rats and mice.
                                     cotton, wool, silk,
                                     leather, and paper.
Oxazepam (604-75-1)...............  Oxazepam is a               NIEHS \1\............  Results of a NTP bioassay
                                     benzodiazepine used                                (TR 443, 1993), which
                                     extensively since the                              reported clear evidence
                                     1960s for the treatment                            of carcinogenicity in
                                     of anxiety and insomnia                            male and female mice.
                                     and in the control of
                                     symptoms of alcohol
                                     withdrawal.
Riddelliine (23246-96-0)..........  Riddelliine is found in     NIEHS \1\............  Results of a NTP bioassay
                                     class of plants growing                            (TR 508, 2003), which
                                     in western US. Cattle,                             reported clear evidence
                                     horses and sheep ingest                            of carcinogenicity in
                                     these toxic plants.                                male and female rats and
                                     Residues have been found                           mice.
                                     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-butadiene-                           animals and limited
                                     styreen resins, styrene-                           evidence of
                                     butadiene rubbers and                              carcinogenicity in
                                     latexes, and unsaturated                           humans (Vol. 82, 2002).
                                     polystyrene resins.
Talc--Two nominations.............  Talc occurs in various      NIEHS \1\............  The NTP deferred
(1) Cosmetic talc.................   geological settings                                consideration of listing
Occupational exposure to talc.....   around the world.                                  talc (asbestiform and
                                     Exposure to general                                non-asbestiform talc) in
                                     population occurs through                          the 20th RoC because its
                                     use of products such as                            2000 review of talc
                                     cosmetics. Occupational                            found confusion in the
                                     exposure occurs during                             scientific literature
                                     mining, milling and                                over the mineral nature
                                     processing.                                        of talc. Given the
                                                                                        confusion over defining
                                                                                        exposure to talc based
                                                                                        on asbestiform fibers,
                                                                                        the NTP 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
                                     topoisomerase II                                   limited evidence of
                                     inhibitors used mainly in                          carcinogenicity in
                                     the treatment of adult                             humans (Vol. 76, 2000).
                                     and childhood leukemia.

[[Page 62279]]

 
Vinyl Mono-Halides as a class.....  Vinyl halides are used in   NIEHS \1\............  Vinyl Fluoride and Vinyl
                                     the production of                                  Bromide are currently
                                     polymers and copolymers.                           listed in the RoC as
                                     Vinyl bromide is mainly                            reasonably anticipated
                                     used in polymers as a                              to be a human carcinogen
                                     flame retardant and in                             and Vinyl Chloride is
                                     the production of                                  currently listed in the
                                     monoacrylic fibers for                             RoC as known to be a
                                     carpet-backing materials.                          human carcinogen in the
                                     Vinyl Chloride is used to                          Reports on Carcinogens.
                                     produced polyvinyl                                Vinyl Mono-Halides:
                                     chloride and copolymers.                           Structural similarities
                                     Vinyl Fluoride is used in                          and 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.
----------------------------------------------------------------------------------------------------------------
\1\ The National Institute of Environmental Health Sciences (NIEHS).
\2\ International Agency for Research on Cancer (IARC).

[FR Doc. 04-23788 Filed 10-22-04; 8:45 am]
BILLING CODE 4140-01-P