[Federal Register Volume 65, Number 66 (Wednesday, April 5, 2000)]
[Notices]
[Pages 17889-17891]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-8310]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program; Call for Public Comments on 
Substances, Mixtures and Exposure Circumstances Proposed for Listing in 
the Report on Carcinogens, Tenth 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), 
Tenth Edition. This Report (previously known as the Annual Report on 
Carcinogens) is a Congressionally mandated listing of known human 
carcinogens and reasonably anticipated human carcinogens and its 
preparation is delegated to the National Toxicology Program by the 
Secretary, Department of Health and Human Services (DHHS). Section 
301(b)(4) of the Public Health Service Act, as amended, provides that 
the Secretary, DHHS shall publish a report which contains a list of all 
substances (1) which either are known to be human carcinogens or may 
reasonably be anticipated to be human carcinogens, and (2) to which a 
significant number of persons residing in the United States (US) are 
exposed. The law also states that the reports should provide available 
information on the nature of exposures, the estimated number of persons 
exposed and the extent to which the implementation of Federal 
regulations decreases the risk to public health from exposure to these 
chemicals.
    The scientific review of the nominated agents, substances, mixtures 
or exposure circumstances involves three separate scientific reviews: 
two Federal review groups and one non-government peer review body (a 
subcommittee of the NTP Board of Scientific Counselors) that meets in 
an open, public forum. Throughout the review process, multiple 
opportunities are provided for public input including at the 
Subcommittee meeting. In reviewing nominations for the RoC, all 
available data and public comments, which are relevant to application 
of the criteria for inclusion or removal of candidate agents, 
substances, mixtures or exposure circumstances or for a change in a 
candidate's classification, are evaluated. The criteria used in the 
review process are as follows:
Known To Be Human Carcinogens
    There is sufficient evidence of carcinogenicity from studies in 
humans which indicates a causal relationship between exposure to the 
agent, substance or mixture and human cancer.
Reasonably Anticipated To Be Human Carcinogens
    There is limited evidence of carcinogenicity from studies in humans 
which indicates that causal interpretation is credible but that 
alternative explanations such as chance, bias or confounding factors 
could not adequately be excluded; or
    There is sufficient evidence of carcinogenicity from studies in 
experimental animals which indicates there is an increased incidence of 
malignant and/or a combination of malignant and benign tumors: (1) in 
multiple species, or at multiple tissue sites, or (2) by multiple 
routes of exposure, or (3) to an unusual degree with regard to 
incidence, site or type of tumor or at onset; or
    There is less than sufficient evidence of carcinogenicity in humans 
or laboratory animals; However, the agent, substance or mixture belongs 
to a well defined, structurally-related class of substances whose 
members are listed in a previous Report on Carcinogens as either a 
known to be human carcinogen, or reasonably anticipated to be human 
carcinogen or there is convincing relevant information that the agent 
acts through mechanisms indicating it would likely cause cancer in 
humans.
    Conclusions regarding carcinogenicity in humans or experimental 
animals are based on scientific judgment, with consideration given to 
all relevant information. Relevant information includes, but is not 
limited to dose response, route of exposure, chemical structure, 
metabolism, pharmacokinetics, sensitive subpopulations, genetic 
effects, or other data relating to mechanism of action or factors that 
may be unique to a given substance. For example, there may be 
substances for which there is evidence of carcinogenicity in laboratory 
animals but there are compelling data indicating that the agent acts 
through mechanisms which do not operate in humans and would therefore 
not reasonably be anticipated to cause cancer in humans.
    A detailed description of the review procedures, including the 
steps in the formal review process, is available at http://ntp-server.niehs.nih.gov or can be obtained by contacting: Dr. C.W. 
Jameson, National Toxicology Program, Report on Carcinogens, MD EC-14, 
P.O. Box 12233, Research Triangle Park, NC 27709; phone: (919) 541-
4096, fax: (919) 541-0144, email: [email protected].

[[Page 17890]]

Public Comment Requested

    The NTP is considering 11 agents, substances, mixtures and exposure 
circumstances for possible review in 2000, as either a new listing in 
or changing the current listing from reasonably anticipated to be a 
human carcinogen to the known to be a human carcinogen category in the 
Tenth Report. These nominations are provided in the following table 
with their Chemical Abstracts Services (CAS) Registry numbers (where 
available) and pending review action. The NTP solicits public input on 
these 11 nominations and asks for relevant information anyone may have 
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, changing the current listing in, or delisting from the 
Tenth Report on Carcinogens will be accepted through June 5, 2000. 
Individuals submitting public comments are asked to include relevant 
contact information (name, affiliation (if any), address, telephone, 
fax, and email). Comments or questions should be directed to Dr. C. W. 
Jameson at the address listed above.

Additional Nominations for Delisting or Listing Encouraged

    The NTP solicits and encourages the broadest participation from 
interested individuals or parties in nominating agents, substances, or 
mixtures for listing in or delisting from the Tenth and future RoCs. 
Nominations should contain a rationale for listing or delisting. 
Appropriate background information and relevant data (e.g. Journal 
articles, NTP Technical Reports, IARC listings, exposure surveys, 
release inventories, etc.), which support a nomination, should be 
provided or referenced when possible. Contact information for the 
nominator should also be included (name, affiliation (if any), address, 
telephone, fax, and email). Nominations should be sent to Dr. Jameson's 
attention at the address given above.

    Dated: March 27, 2000.
Kenneth Olden,
Director, National Toxicology Program.

   Summary for Nominations To Be Reviewed in 2000 for Consideration of Listing In or Delisting From the Tenth
                                              Report on Carcinogens
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                                      Primary uses or
       Nomination/CAS No.                exposures         To be reviewed for         Basis of nomination
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Chloramphenicol (56-75-7).......  Used widely as an        Listing in the      Nominated by RG1 \1\ based on the
                                   antibiotic since the     10th Report.        IARC \2\ identification of
                                   1950s. Veterinary use                        chloramphenicol as a Group 2A-
                                   of chloramphenicol has                       Probable Human Carcinogen (Vol.
                                   resulted in the                              50, 1990). IARC listing based on
                                   occurrence of residues                       findings of limited evidence of
                                   in animal-derived food.                      carcinogenicity in humans based
                                                                                on case reports, which described
                                                                                an unusual succession of
                                                                                leukemia following
                                                                                chloramphenicol-induced aplastic
                                                                                anemia and bone-marrow
                                                                                depression.
Human Papillomaviruses (HPVs)...  HPVs are small, non-     Listing in the      Nominated by RG1 \1\ based on
                                   enveloped viruses that   10th Report.        IARC \2\ finding of sufficient
                                   contain a double-                            evidence of carcinogenicity in
                                   stranded, circular 8                         human epidemiology studies and
                                   kb DNA genome. HPV                           identifying certain human
                                   infections are common                        papillomaviruses as a Group 1--
                                   throughout the world,                        Known Human Carcinogen (Vol. 64,
                                   are highly host-                             1995). HPVs are found in over
                                   specific and, with the                       90% of all invasive cervical
                                   exception of some                            cancers and in a high proportion
                                   ungulate                                     of certain other anogenital
                                   papillomaviruses,                            cancers. Carcinogenicity in
                                   infect only epithelial                       humans has been most firmly
                                   cells.                                       established for HPV-16, but
                                                                                strong evidence of
                                                                                carcinogenicity also exists for
                                                                                certain other HPV types.
Lead and Lead Compounds.........  Widespread uses which    Listing in the      Nominated by RG1 \1\ based on
                                   have included use in     10th Report.        recent published data that
                                   pipes for water                              indicate an excess of cancers in
                                   distribution, lead-                          workers exposed to lead and lead
                                   based paints, lead                           compounds.
                                   additives in gasoline,
                                   and many other
                                   applications.
Methyleugenol (93-15-2).........  Flavoring agent used in  Listing in the      Nominated by RG1 \1\ based on
                                   jellies, baked goods,    10th Report.        recent NTP Technical Report (TR
                                   nonalcoholic                                 491, 1998) reporting clear
                                   beverages, chewing                           evidence of carcinogenic
                                   gum, candy, and ice                          activity of methyleugenol in
                                   cream. Also used as a                        rats and mice based on the
                                   fragrance for many                           increased incidences of liver
                                   perfumes, lotions,                           neoplasms in rats and mice,
                                   detergents and soaps.                        neuroendocrine tumors of the
                                                                                glandular stomach in male and
                                                                                female rats and male mice, and
                                                                                the increased incidences of
                                                                                kidney neoplasms, malignant
                                                                                mesothelioma, mammary gland
                                                                                fibroadenoma, and subcutaneous
                                                                                fibroma and fibroma or
                                                                                fibrosarcoma (combined) in male
                                                                                rats.
Nickel and Nickel Compounds       Widely used in           Listing in the      Action required to complete
 including Metallic Nickel &       commercial               10th Report.        review of Nickel and Nickel
 Nickel Alloys.                    applications for over                        Compounds. This review will be
                                   100 years.                                   of metallic nickel and nickel
                                                                                alloys. Review of nickel
                                                                                compounds for listing in the
                                                                                Report on Carcinogens was
                                                                                completed in 1998.

[[Page 17891]]

 
Estrogens, steroidal............  Estrogens are widely     Listing in the      Nominated by RG1 \1\ based on
                                   used in oral             10th Report.        IARC \2\ identification of
                                   contraceptives and in                        Estrogens, Steroidal as a Group
                                   post-menopausal                              1-Known Human Carcinogen (Vol.
                                   therapy for women.                           72, 1999) IARC listing based on
                                                                                a consistent, strongly positive
                                                                                association between exposure to
                                                                                a number of estrogenic
                                                                                substances and risk of
                                                                                endometrial and breast cancer in
                                                                                women.
Talc (14807-96-6) (Non-           Talc (non-asbestiform)   Listing in the      Nominated by RG1 \1\ based on NTP
 Asbestiform).                     occurs in various        10th Report.        Technical Report (TR 421, 1993)
                                   geological settings                          which reported clear evidence of
                                   around the world.                            carcinogenic activity of talc
                                   Occupational exposure                        (non-asbestiform) based on
                                   occurs during mining,                        increased incidences of alveolar/
                                   milling and                                  bronchiolar adenomas and
                                   processing. Exposure                         carcinomas of the lung in female
                                   to general population                        rats and also recently published
                                   occurs through use of                        epidemiology studies that
                                   products such as                             suggests that talc exposure
                                   cosmetics.                                   among pottery workers has been
                                                                                associated with lung cancer, and
                                                                                ovarian neoplasms in women.
Talc (14807-96-6) (Containing     Talc (containing         Listing in the      Nominated by RG1 \1\ based on
 Asbestiform Fibers).              asbestiform fibers)      10th Report.        IARC \2\ identification of talc
                                   occurs in various                            (containing asbestiform fibers)
                                   geological settings                          as a Group 1-Known Human
                                   around the world.                            Carcinogen (Sup 7, 1987). IARC
                                   Occupational exposure                        listing based on the observed
                                   occurs during mining,                        association between exposure to
                                   milling and processing.                      talc containing asbestiform
                                                                                fibers and mesothelioma in
                                                                                humans.
Trichloroethylene (TCE) (79-01-   Trichloroethylene is     Upgrade to Known..  Recommended by RG1 \1\ to be
 6).                               widely used as a                             upgraded to a known human
                                   solvent with 80-90%                          carcinogen based on recent
                                   used worldwide for                           published data that indicate an
                                   degreasing metals.                           excess of kidney cancers in
                                                                                workers exposed to
                                                                                trichloroethylene.
Broad Spectrum UV Radiation.....  Solar and artificial     Listing in the      Review of UVA, UVB and UVC
                                   sources of ultraviolet   10th Report.        recommended by RG2 \3\ based on
                                   radiation.                                   earlier Report on Carcinogens
                                                                                review of solar UV radiation.
Wood Dust.......................  It is estimated that at  Listing in the      Nominated by the Occupational
                                   least two million        10th Report.        Safety and Health Administration
                                   people are routinely                         based on IARC \2\ identification
                                   exposed occupationally                       of wood dust as a Group 1-Known
                                   to wood dust                                 Human Carcinogen (Vol. 62,
                                   worldwide. Non-                              1995). IARC listing based on
                                   occupational exposure                        increases in cancer,
                                   also occurs. The                             particularly cancer of the nasal
                                   highest exposures have                       cavities and paranasal sinuses,
                                   generally been                               associated with exposure to wood
                                   reported in wood                             dust.
                                   furniture and cabinet
                                   manufacture,
                                   especially during
                                   machine sanding and
                                   similar operations.
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\1\ The NIEHS Review Committee for the Report on Carcinogens (RG1).
\2\ International Agency For Research On Cancer (IARC).
\3\ The NTP Executive Committee* Interagency Working Group for the Report on Carcinogens (RG2).
*Agencies from the NTP Executive Committee represented on RG2 include: Agency for Toxic Substances and Disease
  Registry (ATSDR), Consumer Product Safety Commission (CPSC), Environmental Protection Agency (EPA), National
  Center for Environmental Health of the Centers for Disease Control and Prevention (NCEH/CDC), National Center
  for Toxicological Research of the Food and Drug Administration (NCTR/FDA), National Institute for Occupational
  Safety and Health/CDC (NIOSH/CDC), Occupational Safety and Health Administration (OSHA), National Cancer
  Institute of the National Institutes of Health (NCI/NIH), and National Institute of Environmental Health
  Sciences/NIH(NIEHS/NIH)

[FR Doc. 00-8310 Filed 4-4-00; 8:45 am]
BILLING CODE 4140-01-P