[Federal Register Volume 70, Number 200 (Tuesday, October 18, 2005)]
[Notices]
[Pages 60548-60554]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-20729]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Toxicology Program (NTP); Report on Carcinogens; Status 
of Nominations to the 12th Report on Carcinogens (RoC): Request for 
Comments and Nominations of Scientific Experts

AGENCY: National Institute of Environmental Sciences (NIEHS), National 
Institutes of Health (NIH), HHS.

[[Page 60549]]


ACTION: Request for Comments and Nominations of Scientific Experts.

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SUMMARY: The NTP invites public comments on an updated list of 
nominations proposed for review in the 12th RoC and the nomination of 
scientists who have expertise and/or knowledge relevant to the 
evaluation of carcinogenicity for these nominations (see SUPPLEMENTARY 
INFORMATION). Information on the nominations under consideration for 
the RoC can be obtained at the NTP Web site http://ntp.niehs.nih.gov 
(select ``Report on Carcinogens'') or by contacting Dr. C.W. Jameson at 
the address provided below.

DATES: Comments and nominations will be accepted until November 17, 
2005.

ADDRESSES: All correspondence should be directed to 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: 
<a href="/cdn-cgi/l/email-protection#3d575c50584e52537d535458554e13535455135a524b"><span class="__cf_email__" data-cfemail="3d575c50584e52537d535458554e13535455135a524b">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION:

Background

    This notice provides an update on the current status of and/or 
additions to the list of nominations identified in earlier Federal 
Register notices relevant to the 12th RoC [69FR28940 (May 19, 2004) and 
69FR62276 (October 25, 2004)]. All but the newly identified nomination 
of formaldehyde were announced in earlier Federal Register notices. Any 
additional nominations for the 12th RoC or modifications to the 
nominations in the attached table will be announced in future Federal 
Register notices.

Request for Comments on Nominations to the RoC

    The following table identifies the nominations that the NTP has 
under consideration for review as either a new listing in the RoC or as 
a change in the current listing. These nominations are provided with 
their Chemical Abstracts Services (CAS) Registry numbers (where 
available) and pending review action. The NTP solicits public input on 
these nominations and asks for relevant information concerning their 
carcinogenicity as well as current data on production, patterns of use, 
or human exposure. 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 (69FR28940) and/or the October 25, 2004 Federal 
Register notice (69FR62276) need not re-submit their comments as they 
are already part of the public record. Individuals submitting public 
comments are asked to include relevant contact information [name, 
affiliation (if any), address, telephone, fax, and e-mail] and 
sponsoring organization, if applicable. Written submissions will be 
made available on the NTP Web site as they are received (http://ntp.niehs.nih.gov/ select ``Report on Carcinogens'') and added to the 
public record.

Request for Nominations of Scientific Experts

    The NTP solicits nominations of scientists who have expertise and/
or knowledge relevant to the evaluation of carcinogenicity for the 
selected nominations. These scientists should have expertise in various 
aspects of toxicology, epidemiology, carcinogenesis, or other relevant 
areas of science (e.g., genetic toxicity, metabolism, etc.) and/or 
experience with the agent being reviewed. The experts may be used to 
write and/or review the background documents prepared on selected 
nominations. Nominations of scientists should include contact 
information for the nominee [name, affiliation (if any), address, 
telephone, fax, and e-mail], the specific nominated agent(s) (listed in 
the table below) for which they are being recommended as an expert, and 
a curriculum vitae (if possible). Contact information for the nominator 
must also be provided.

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 future RoCs. Nominations should contain a 
rationale for review. Appropriate background information and relevant 
data [e.g., journal articles, NTP Technical Reports, International 
Agency for Research on Cancer (IARC) listings, exposure surveys, 
release inventories, etc.] that 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].

Background Information on the Report on Carcinogens

    The RoC is a congressionally mandated document [Section 301(b)(4) 
of the Public Health Services Act, 42 U.S.C. 241(b)(4)], published by 
the Secretary of Health and Human Services (HHS), that identifies 
agents, substances, mixtures, or exposure circumstances (collectively 
referred to as ``substances'') that may pose a carcinogenic hazard to 
human health. The Secretary, HHS, has delegated responsibility for 
preparing the draft report to the NTP. Substances are listed in the RoC 
as either known to be a human carcinogen or reasonably anticipated to 
be a human carcinogen. Review of nominations (substances that are under 
consideration for listing or removing from the RoC) involves a multi-
step scientific review process with opportunity for public comment.

    Dated: October 6, 2005.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.

                       Status of Nominations To Be Reviewed for the Report on Carcinogens
----------------------------------------------------------------------------------------------------------------
                                    Primary uses or                            Basis for
       Nomination/CAS No.              exposures           Nominator          nomination            Status
----------------------------------------------------------------------------------------------------------------
 1 Herbal remedies containing     Several             NIEHS.............  Herbal remedies     Review for
 aristolochic acid.                Aristolochia                            containing the      possible listing
*Note--this nomination was         species (notably                        plant genus         in 12th RoC.
 previously identified as          A. contorta, A.                         Aristolochia:
 ``Aristolochia-Related Herbal     debilis, A.                             IARC 2 finding of
 Remedies''.                       fangchi and A.                          sufficient
                                   manshuriensis)                          evidence of
                                   have been used in                       carcinogenicity
                                   traditional                             in humans (IARC
                                   Chinese medicine                        Monograph Vol.
                                   as                                      82, 2002).
                                   antirheumatics,
                                   as diuretics, in
                                   the treatment of
                                   edema, and for
                                   other conditions
                                   such as
                                   hemorrhoids,
                                   coughs, and
                                   asthma.

[[Page 60550]]

 
Aristolochic Acid...............  Aristolochic acid,  NIEHS.............  Naturally           Review for
                                   the principle                           occurring           possible listing
                                   extract from                            mixtures of         in 12th RoC.
                                   Aristolochia, is                        aristolochic
                                   a mixture of                            acids: IARC 2
                                   nitrophenanthrene                       finding of
                                   carboxylic acids.                       sufficient
                                                                           evidence of
                                                                           carcinogenicity
                                                                           in animals and
                                                                           limited evidence
                                                                           in humans (IARC
                                                                           Monograph Vol.
                                                                           82, 2002).
Asphalt fumes...................  Asphalt is a        Private Individual  Human               Defer review of
                                   petroleum product                       epidemiological     nomination until
                                   used in paving                          studies have        the 13th RoC.
                                   and roofing                             reported an
                                   operations.                             increased risk of
                                   Asphalt fumes are                       lung cancer among
                                   a cloud of small                        workers exposed
                                   particles                               to asphalt fumes
                                   generated after                         and asphalt fumes
                                   volatilization of                       caused skin
                                   asphalt                                 tumors in
                                   aggregates.                             experimental
                                                                           animals.
                                                                           Additionally,
                                                                           known human
                                                                           carcinogens
                                                                           (polycyclic
                                                                           aromatic
                                                                           hydrocarbons or
                                                                           PAHs) have been
                                                                           found in asphalt
                                                                           fumes.
Atrazine (192-24-9).............  Atrazine is an      NIEHS.............  IARC 2 finding of   Defer review of
                                   herbicide used to                       sufficient          nomination until
                                   control grass and                       evidence of         the 13th RoC.
                                   broad-leaved                            carcinogenicity
                                   weeds. Atrazine                         in animals (IARC
                                   has been detected                       Monograph Vol.
                                   at levels that                          73, 1999).
                                   exceeded or
                                   approached the
                                   maximum
                                   contaminant level
                                   (MCL) for
                                   atrazine in 200
                                   community surface
                                   drinking water
                                   systems.
Benzofuran (271-89-6)...........  Benzofuran is       NIEHS.............  Results of a NTP    Defer review of
                                   produced by                             bioassay (NTP       nomination until
                                   isolation from                          Technical Report    the 13th RoC.
                                   coal-tar oils.                          370, 1989) 3,
                                   Benzofuran is                           which reported
                                   used in the                             clear evidence of
                                   manufacture of                          carcinogenicity
                                   coumarone-indene                        in male and
                                   resins, which                           female mice and
                                   harden when                             some evidence of
                                   heated and are                          carcinogenicity
                                   used to make                            in female rats.
                                   floor tiles and
                                   other products.
Captafol (2425-06-01)...........  Captafol is a       NIEHS.............  IARC 2 finding of   Review for
                                   fungicide that                          sufficient          possible listing
                                   has been widely                         evidence of         in 12th RoC.
                                   used since 1961                         carcinogenicity
                                   for the control                         in animals (IARC
                                   of fungal                               Monograph Vol.
                                   diseases in                             53, 1991). IARC
                                   fruits,                                 also noted that
                                   vegetables, and                         captafol is
                                   some other                              positive in many
                                   plants. Use of                          genetic assays
                                   captafol in the                         including the in-
                                   United States was                       vivo assay for
                                   banned in 1999.                         dominant lethal
                                                                           mutation.
1 Cobalt-tungsten carbide         Cobalt-tungsten     NIEHS.............  Recent human        Review for
 powders and hard metals.          carbide hard-                           cancer studies on   possible listing
*Note--This nomination was         metals are                              the hard metal      in 12th RoC.
 previously identified as          manufactured by a                       manufacturing
 ``Cobalt/Tungsten-Carbide Hard    process of powder                       industry showing
 Metal Manufacturing''.            metallurgy from                         an association
                                   tungsten and                            between exposure
                                   carbon (tungsten                        to hard metals
                                   carbide), and                           (cobalt tungsten-
                                   small amounts of                        carbide) and lung
                                   other metallic                          cancer.
                                   compounds using
                                   cobalt as a
                                   binder. They 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.

[[Page 60551]]

 
Di (2-ethylhexyl) phthalate       DEHP is mainly      Private Individual  Currently listed    Review for
 (DEHP) (117-81-7).                used as a                               in the RoC as       possible removal
                                   plasticizer in                          reasonably          of listing in
                                   polyvinyl                               anticipated to be   12th RoC.
                                   chloride (PVC)                          a human
                                   resins for                              carcinogen.
                                   fabricating                            IARC 2
                                   flexible vinyl                          reclassification
                                   products. PVC                           as not
                                   resins have been                        classifiable as
                                   used to                                 to its
                                   manufacture toys,                       carcinogenicity
                                   dolls, vinyl                            to humans (Group
                                   upholstery,                             3) (IARC
                                   tablecloths, and                        Monograph Vol.
                                   many other                              77, 2000). IARC
                                   products.                               stated 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        NIEHS.............  IARC 2 finding of   Review for
 cisplatin and bleomycin.          combination with                        sufficient          possible listing
                                   cisplatin and                           evidence of         in 12th RoC.
                                   bleomycin is used                       carcinogenicity
                                   to treat                                in humans (IARC
                                   testicular germ                         Monograph Vol.
                                   cell cancers.                           76, 2000).
Etoposide (33419-42-0)..........  Etoposide is a DNA  NIEHS.............  IARC 2 finding of   Review for
                                   topoisomerase II                        limited evidence    possible listing
                                   inhibitor used in                       of                  in 12th RoC.
                                   chemotherapy for                        carcinogenicity
                                   non-Hodgkin's                           in humans (IARC
                                   lymphoma, small-                        Monograph Vol.
                                   cell lung cancer,                       76, 2000).
                                   testicular
                                   cancer,
                                   lymphomas, and a
                                   variety of
                                   childhood
                                   malignancies.
Formaldehyde (50-00-0)..........  Formaldehyde is     NIEHS.............  Formaldehyde (gas)  Review for
                                   primarily used in                       is currently        possible
                                   the production of                       listed in the RoC   reclassification
                                   resins that are                         as reasonably       of listing status
                                   used in the                             anticipated to be   in 12th RoC.
                                   production of                           a human
                                   many different                          carcinogen.
                                   products                                Nominated for
                                   including                               reconsideration
                                   plastics,                               based on the 2004
                                   adhesives and                           IACR 2 review,
                                   binders for wood                        which concluded
                                   products, pulp                          that there was
                                   and paper,                              sufficient
                                   synthetic fibers,                       evidence for the
                                   and in textile                          carcinogenicity
                                   finishing. It is                        of formaldehyde
                                   also used as a                          in humans (IARC
                                   disinfectant and                        Monograph Vol.
                                   preservative and                        88, 2004).
                                   as an
                                   intermediate for
                                   many industrial
                                   chemicals.

[[Page 60552]]

 
1 Certain Glass Wool Fibers.....  Glass wool fibers,  North American      Glass wool          Review for
*Note--This nomination was         which are a type    Insulation          (respirable size)   possible listing
 previously identified as          of synthetic        Manufacturers       is currently        in 12th RoC.
 ``Glass wool (respirable size):   vitreous fibers,    Association         listed in the RoC
 Two nominations: (1) Insulation   are an inorganic    nominated glass     as reasonably
 glass wool fibers, and (2)        fibrous material    wool (respirable    anticipated to be
 Special purpose glass fibers''.   manufactured        size) for           a human
                                   primarily from      delisting.          carcinogen.
                                   glass and          NIEHS recommended   Insulation glass
                                   processed           that the            wool: IARC 2
                                   inorganic oxides.   nomination be       finding of
                                   The composition     defined as          limited evidence
                                   of these fibers     ``certain glass     of
                                   may vary            wool fibers''       carcinogenicity
                                   substantially       because of the      in animals and
                                   because of          considerable        evaluation as not
                                   differences in      differences in      classifiable as
                                   end-use,            the composition     to its
                                   manufacturing       of glass wool       carcinogenicity
                                   requirements, and   fibers.             to humans (Group
                                   biopersistence                          3) (IARC
                                   considerations.                         Monograph Vol.
                                   The major uses of                       81, 2002).
                                   glass wool are in                      Special-purpose
                                   thermal,                                glass fibers:
                                   electrical, and                         IARC 2 finding of
                                   acoustical                              sufficient
                                   insulation,                             evidence of
                                   weatherproofing,                        carcinogenicity
                                   and filtration                          in animals (IARC
                                   media. Some glass                       Monograph Vol.
                                   wool fibers                             81, 2002).
                                   (special purpose
                                   fibers) are used
                                   for high-
                                   efficiency air
                                   filtration media,
                                   and acid battery
                                   separators.
Metalworking Fluids.............  Metal working       NIEHS.............  Recent human        Review for
                                   fluids are                              cancer studies of   possible listing
                                   complex mixtures                        metal working       in 12th RoC.
                                   that may contain                        fluids that show
                                   mixtures of oil,                        an association
                                   emulsifiers, anti-                      between exposure
                                   weld agents,                            to these
                                   corrosion                               materials and
                                   inhibitors,                             cancer at several
                                   extreme pressure                        tissue sites.
                                   additives,
                                   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.
ortho-Nitrotoluene (88-72-2)....  ortho-Nitrotoluene  NIEHS.............  Results of a NTP    Review for
                                   is used to                              bioassay (NTP       possible listing
                                   synthesize                              Technical Report    in 12th RoC.
                                   agricultural and                        504, 2002) 3,
                                   rubber chemicals,                       which reported
                                   azo and sulfur                          clear evidence of
                                   dyes, and dyes                          carcinogenicity
                                   for cotton, wool,                       in rats and mice.
                                   silk, leather,
                                   and paper.
Oxazepam (604-75-1).............  Oxazepam is a       NIEHS.............  Results of a NTP    Defer review of
                                   benzodiazepine                          bioassay (NTP       nomination until
                                   used extensively                        Technical Report    the 13th RoC.
                                   since the 1960s                         443, 1993) 3,
                                   for the treatment                       which reported
                                   of anxiety and                          clear evidence of
                                   insomnia and in                         carcinogenicity
                                   the control of                          in male and
                                   symptoms of                             female mice.
                                   alcohol
                                   withdrawal.
Riddelliine (23246-96-0)........  Riddelliine is      NIEHS.............  Results of a NTP    Review for
                                   found in class of                       bioassay (NTP       possible listing
                                   plants growing in                       Technical Report    in 12th RoC.
                                   western United                          508, 2003) 3,
                                   States. Cattle,                         which reported
                                   horses, and sheep                       clear evidence of
                                   ingest these                            carcinogenicity
                                   toxic plants.                           in male and
                                   Residues have                           female rats and
                                   been found in                           mice.
                                   milk and honey.
Styrene (100-42-5)..............  Styrene is used in  Private Individual  IARC 2 finding of   Review for
                                   the production of                       limited evidence    possible listing
                                   polystyrene,                            of                  in 12th RoC.
                                   acrylonitrile-                          carcinogenicity
                                   butadiene-styrene                       in animals and
                                   resins, styrene-                        limited evidence
                                   butadiene rubbers                       of
                                   and latexes, and                        carcinogenicity
                                   unsaturated                             in humans (IARC
                                   polystyrene                             Monograph Vol.
                                   resins.                                 82, 2002).

[[Page 60553]]

 
Talc (Two nominations)..........  Talc occurs in      NIEHS.............  The NTP deferred    Withdrawn from
(1) Cosmetic talc...............   various                                 consideration of    review.
(2) Occupational exposure to       geological                              listing talc
 talc.                             settings around                         (asbestiform and
                                   the world.                              non-asbestiform
                                   Exposure to                             talc) in the 10th
                                   general                                 RoC because its
                                   population occurs                       2000 review of
                                   through use of                          talc found that
                                   products such as                        there has been
                                   cosmetics.                              considerable
                                   Occupational                            confusion over
                                   exposure occurs                         the mineral
                                   during mining,                          nature and
                                   milling, and                            consequences of
                                   processing.                             exposure to talc,
                                                                           both containing
                                                                           asbestiform
                                                                           fibers and not
                                                                           containing
                                                                           asbestiform
                                                                           fibers. It has
                                                                           become evident
                                                                           that the
                                                                           literature on
                                                                           both forms of
                                                                           talc, with a few
                                                                           exceptions,
                                                                           provides an
                                                                           inadequate
                                                                           characterization
                                                                           of the actual
                                                                           materials under
                                                                           study to enable
                                                                           one to reach
                                                                           definitive
                                                                           conclusions
                                                                           concerning the
                                                                           specific
                                                                           substances
                                                                           responsible for
                                                                           the range of
                                                                           adverse health
                                                                           outcomes reported.
Teniposide (29767-20-2).........  Teniposide is a     NIEHS.............  IARC 2 finding of   Review for
                                   DNA topoisomerase                       limited evidence    possible listing
                                   II inhibitors                           of                  in 12th RoC.
                                   used mainly in                          carcinogenicity
                                   the treatment of                        in humans (IARC
                                   adult and                               Monograph Vol.
                                   childhood                               76, 2000).
                                   leukemia.
Vinyl Mono-Halides as a class...  Vinyl halides are   NIEHS.............  Vinyl fluoride and  Defer review of
                                   used in the                             vinyl bromide are   nomination until
                                   production of                           currently listed    the 13th RoC.
                                   polymers and                            in the RoC as
                                   copolymers. Vinyl                       reasonably
                                   bromide is mainly                       anticipated to be
                                   used in polymers                        a human
                                   as a flame                              carcinogen and
                                   retardant and in                        vinyl chloride is
                                   the production of                       currently listed
                                   monoacrylic                             in the RoC as a
                                   fibers for carpet-                      known to be a
                                   backing                                 human carcinogen.
                                   materials. Vinyl                       Vinyl mono-
                                   chloride is used                        halides:
                                   to produce                              Structural
                                   polyvinyl                               similarities and
                                   chloride and                            common mechanisms
                                   copolymers. Vinyl                       of tumor
                                   fluoride is used                        formation.
                                   in the production
                                   of 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 Nomination has been redefined based on public comments received from earlier Federal Register notices and/or
  review of the literature.
2 International Agency for Research on Cancer (IARC). IARC Monographs are available from http://monographs.iarc.fr/.
3 NTP Technical Reports are available at http://ntp.niehs.nih.gov/ see ``NTP Study Reports.''


[[Page 60554]]

[FR Doc. 05-20729 Filed 10-17-05; 8:45 am]
BILLING CODE 4140-01-P


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