Federal Register: July 24, 2001 (Volume 66, Number 142)
DOCID: FR Doc 01-18391
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
NOTICE: NOTICES
ACTION: National Toxicology Program:
SUBJECT CATEGORY:
National Toxicology Program; Call for Public Comments on 16 Substances, Mixtures and Exposure Circumstances Proposed for Listing in the Report on Carcinogens, Eleventh Edition
DOCUMENT SUMMARY:
Background
The National Toxicology Program (NTP) announces its intent to review additional agents, substances, mixtures and exposure circumstances for possible listing in the Report on Carcinogens (RoC), Eleventh Edition that is scheduled for publication in 2004. This Report (previously known as the Annual Report on Carcinogens) is a Congressionally mandated listing of known human carcinogens and reasonably anticipated human carcinogens and its preparation is delegated to the National Toxicology Program by the Secretary, Department of Health and Human Services (DHHS). Section 301(b)(4) of the Public Health Service Act, as amended, provides that the Secretary, DHHS shall publish a report, which contains a list of all substances (1) which either are known to be human carcinogens or may reasonably be anticipated to be human carcinogens, and (2) to which a significant number of persons residing in the United States (US) are exposed. The law also states that the reports should provide available information on the nature of exposures, the estimated number of persons exposed and the extent to which the implementation of Federal regulations decreases the risk to public health from exposure to these chemicals.
The scientific review of the nominated agents, substances, mixtures or exposure circumstances involves three separate scientific reviews: Two Federal review groups and one nongovernment peer review body (a subcommittee of the NTP Board of Scientific Counselors) that meets in an open, public forum. Throughout the review process, multiple opportunities are provided for public input including comment at the public meeting of the NTP Board Subcommittee. In reviewing nominations for the RoC, all available data and public comments are considered in the application of the criteria for inclusion or removal of candidate agents, substances, mixtures or exposure circumstances or for a change in a candidate's classification. The criteria used in the review process are as follows:
Known To Be Human Carcinogens
There is sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer.
Reasonably Anticipated To Be Human Carcinogens
There is limited evidence of carcinogenicity from studies in humans which indicates that causal interpretation is credible but that alternative explanations such as chance, bias or confounding factors could not adequately be excluded; or
There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors: (1) In multiple species, or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site or type of tumor or at onset; or
There is less than sufficient evidence of carcinogenicity in humans or laboratory animals; However, the agent, substance or mixture belongs to a well defined, structurallyrelated class of substances whose members are listed in a previous Report on Carcinogens as either a known to be human carcinogen, or reasonably anticipated to be human carcinogen or there is convincing relevant information that the agent acts through mechanisms indicating it would likely cause cancer in humans.
Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment, with consideration given to all relevant information. Relevant information includes, but is not limited to dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub populations, genetic effects, or other data relating to mechanism of action or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would therefore not reasonably be anticipated to cause cancer in humans.
A detailed description of the review procedures, including the steps in the formal review process, is available at http://ntp server.niehs.nih.gov or can be obtained by contacting: Dr. C.W. Jameson, National Toxicology Program, Report on Carcinogens, 79 Alexander Drive, Building 4401, Room 3118, P.O. Box 12233, Research Triangle Park, NC 27709; phone: (919) 5414096, fax: (919) 5410144, email: jameson@niehs.nih.gov. Public Comment Requested
The following table identifies the 16 nominations the NTP may
consider for review in 2001 or 2002, as either a new listing in or
changing the current listing from reasonably anticipated to be a human
carcinogen to the known to be a human carcinogen category in the
Eleventh Report. These nominations are provided with their Chemical
Abstracts Services (CAS) Registry numbers (where available) and pending
review action. Additional nominations for the Eleventh Report or
modifications to the nominations in the attached table may be
identified and would be announced in future Federal Register notices.
The NTP solicits public input on these 16 nominations and asks for relevant
[[Page 38431]]
information concerning their carcinogenesis, as well as current
production data, use patterns, or human exposure information. The NTP
also invites interested parties to identify any scientific issues
related to the listing of a specific nomination in the RoC that they
feel should be addressed during the reviews. Comments concerning these
nominations for listing in or changing the current listing in the
Eleventh Report on Carcinogens will be accepted through September 24,
2001. Individuals submitting public comments are asked to include
relevant contact information (name, affiliation (if any), address,
telephone, fax, and email). Comments or questions should be directed to Dr. C.W. Jameson at the address listed above.
Additional Nominations for Delisting or Listing Encouraged
The NTP solicits and encourages the broadest participation from
interested individuals or parties in nominating agents, substances, or
mixtures for listing in or delisting from the Eleventh and future RoCs.
Nominations should contain a rationale for listing or delisting.
Appropriate background information and relevant data (e.g. Journal
articles, NTP Technical Reports, IARC listings, exposure surveys,
release inventories, etc.), which support a nomination, should be
provided or referenced when possible. Contact information for the
nominator should also be included (name, affiliation (if any), address,
telephone, fax, and email). Nominations should be sent to Dr. Jameson's attention at the address given above.
Dated: July 12, 2001.
Kenneth Olden,
Director, National Toxicology Program.
Summary for Agents, Substances, Mixtures or Exposure Circumstances to be Reviewed in 20012002 for Possible
Listing in the Report on Carcinogens, Eleventh Edition
Nomination to be reviewed/CAS No. Primary uses or exposures Nominated by Basis for nomination
1Amino2,4dibromoanthraquinone 1Amino2,4 NIEHS \1\............ Results of NTP Bioassay
(81492). dibromoanthraquinone is (TR 383, 1996) that
an anthraquinonederived reported clear evidence
vat dye that is used in of carcinogenicity at
the textile industry. multiple tumor sites in
multiple species of
experimental animals.
2Amino3,4dimethylimidazo[4,5 MeIQ is a heterocyclic NIEHS \1\............ IARC \2\ finding of
f]quinoline (MeIQ) (77094112). amine that is formed sufficient evidence of
during heating or cooking carcinogenicity in
and is found in cooked experimental animals
meat and fish. (Vol. 56; 1993).
Cobalt Sulfate (10026241)....... Cobalt sulfate is used in NIEHS \1\............ Results of NTP Bioassay
electroplating and (TR 471, 998) which
electrochemical reported clear evidence
industries. It is also of carcinogenic activity
used as a coloring agent in female F344/N rats
for ceramics, a drying and male and female
agent in inks, paints, B63F1 mice and some
varnishes and linoleum, evidence of carcinogenic
and has been added to activity in male F344/N
animal feed as a mineral rats. supplement.
Diazoaminobenzene (DAAB) (13635 DAAB is used as an NIEHS \1\............ Results of research
6). intermediate, complexing supported the by the NTP
agent, polymer additive that demonstrated this
and also to promote chemical is
adhesion of natural quantitatively
rubber to steel. metabolized to benzene
(a known human
carcinogen).
Diethanolamine (DEA) (111422)... DEA is used in the Dr. Franklin Mirer of Results of NTP Bioassay
preparation of the United Auto (TR 478, 1999) which
surfactants used in Workers. reported clear evidence
liquid laundry, of carcinogenic activity
dishwashing detergents, in male and female
cosmetics, shampoos, and B6C3F1 mice.
hair conditioners and in textile processing,
industrial gas
purification and as an anticorrosion agent.
Hepatitis B Virus (HBV)........... HBV is a small DNA NIEHS \1\............ IARC \2\ finding of
enveloped virus that is sufficient evidence of
transmitted by carcinogenicity in
percutaneous or humans (Vol. 59, 1994).
permuscosal exposure to
infectious blood or body
fluids that contain blood.
Hepatitis C Virus (HCV)........... HCV is an RNAenveloped NIEHS \1\............ IARC \2\ finding of
virus that is transmitted sufficient evidence of
mainly by percutaneous carcinogenicity in
exposure to infectious humans (Vol. 59, 1994). blood and less
efficiently by
permuscosal exposure to
infectious blood or body
fluids that contain blood.
High Risk Human Papillomaviruses HPVs are small, non NIEHS \1\............ IARC \2\ finding of
(HPVs). enveloped viruses that sufficient evidence of
infect the skin and oral carcinogenicity in
and genital mucosa. HPV humans (Vol. 70, 1997). infections are common
throughout the world.
XRadiation and GAMMA (
Neutrons.......................... Exposure to neutrons NIEHS \1\............ IARC \2\ finding of
normally occurs from a sufficient evidence of
mixed irradiation field carcinogenicity in
in which neutrons are a humans (Vol. 75, 2000). minor component. The
exceptions are exposure
of patients to neutron
radiotherapy beams and exposures of aircraft
passengers and crew.
Occupational exposure to lead or Major occupational NIEHS \1\............ Recent published data
lead compounds. exposures are in the lead that indicate an excess
smelting and refining of cancers in workers
industries, battery exposed to lead and lead
manufacturing plants, compounds.
steel welding or cutting
operations, construction, and firing ranges.
Naphthalene (91203)............. Naphthalene is used as an NIEHS \1\............ Results of NTP Bioassay
intermediate in the (TR 500, 2000) that
synthesis of many reported clear evidence
industrial chemicals, an of carcinogenicity in
ingredient in some moth male & female rats and
repellants and toilet some evidence in female
bowl deodorants, as an mice. antiseptics for
irrigating animal wounds
and to control lice on
livestock and poultry.
Nitrobenzene (98953)............ Nitrobenzene is used NIEHS \1\............ IARC \2\ finding
mainly in the production sufficient of evidence
of aniline, itself a of carcinogenicity in
major chemical experimental animals
intermediate in the (Vol. 65, 1996). production of dyes.
Nitromethane (75525)............ Nitromethane is used as an NIEHS \1\............ Results of NTP Bioassay
additive to many (TR 461, 1997) that
halogenated solvents and reported clear evidence
aerosol propellants as a of carcinogenicity in
stabilizer. It can also male & female mice and
be used in specialized clear evidence in female
fuels and in explosives. rats.
Phenylimidazopyridine [PhIP, PhIP is a heterocyclic Dr. Takashi Sugimura, Nomination based on Dr.
(105650235)]. amine that is formed President Emeritus, Sugimura's recent
during heating or cooking National Cancer reviews of the
and is found in cooked Center of Japan. carcinogenicity of
meat and fish. heterocyclic amines.
4,4'Thiodianiline (139651)..... 4,4'Thiodianiline has NIEHS \1\............ IARC \2\ finding of
been produced sufficient evidence of
commercially since the carcinogenicity in
early 1940's as an experimental animals
intermediate of several (Suppl 7, 1987). and
diazo dyes. result of NTP Bioassay
studies that
demonstrated clear
evidence of
carcinogenicity in mice
and rats (TR047, 1978).
\1\ The National Institute of Environmental Health Sciences (NIEHS). \2\ International Agency for Research on Cancer (IARC).
[FR Doc. 0118391 Filed 72301; 8:45 am]
BILLING CODE 414001P
SUMMARY:
Carcinogens Report, Eleventh Edition—; Agents, substances, mixtures, and exposure circumstances; listing; comment request,
DOCUMENT BODY 2:
Background
The National Toxicology Program (NTP) announces its intent to review additional agents, substances, mixtures and exposure circumstances for possible listing in the Report on Carcinogens (RoC), Eleventh Edition that is scheduled for publication in 2004. This Report (previously known as the Annual Report on Carcinogens) is a Congressionally mandated listing of known human carcinogens and reasonably anticipated human carcinogens and its preparation is delegated to the National Toxicology Program by the Secretary, Department of Health and Human Services (DHHS). Section 301(b)(4) of the Public Health Service Act, as amended, provides that the Secretary, DHHS shall publish a report, which contains a list of all substances (1) which either are known to be human carcinogens or may reasonably be anticipated to be human carcinogens, and (2) to which a significant number of persons residing in the United States (US) are exposed. The law also states that the reports should provide available information on the nature of exposures, the estimated number of persons exposed and the extent to which the implementation of Federal regulations decreases the risk to public health from exposure to these chemicals.
The scientific review of the nominated agents, substances, mixtures or exposure circumstances involves three separate scientific reviews: Two Federal review groups and one nongovernment peer review body (a subcommittee of the NTP Board of Scientific Counselors) that meets in an open, public forum. Throughout the review process, multiple opportunities are provided for public input including comment at the public meeting of the NTP Board Subcommittee. In reviewing nominations for the RoC, all available data and public comments are considered in the application of the criteria for inclusion or removal of candidate agents, substances, mixtures or exposure circumstances or for a change in a candidate's classification. The criteria used in the review process are as follows:
Known To Be Human Carcinogens
There is sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer.
Reasonably Anticipated To Be Human Carcinogens
There is limited evidence of carcinogenicity from studies in humans which indicates that causal interpretation is credible but that alternative explanations such as chance, bias or confounding factors could not adequately be excluded; or
There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors: (1) In multiple species, or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site or type of tumor or at onset; or
There is less than sufficient evidence of carcinogenicity in humans or laboratory animals; However, the agent, substance or mixture belongs to a well defined, structurallyrelated class of substances whose members are listed in a previous Report on Carcinogens as either a known to be human carcinogen, or reasonably anticipated to be human carcinogen or there is convincing relevant information that the agent acts through mechanisms indicating it would likely cause cancer in humans.
Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment, with consideration given to all relevant information. Relevant information includes, but is not limited to dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub populations, genetic effects, or other data relating to mechanism of action or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would therefore not reasonably be anticipated to cause cancer in humans.
A detailed description of the review procedures, including the steps in the formal review process, is available at http://ntp server.niehs.nih.gov or can be obtained by contacting: Dr. C.W. Jameson, National Toxicology Program, Report on Carcinogens, 79 Alexander Drive, Building 4401, Room 3118, P.O. Box 12233, Research Triangle Park, NC 27709; phone: (919) 5414096, fax: (919) 5410144, email: jameson@niehs.nih.gov. Public Comment Requested
The following table identifies the 16 nominations the NTP may
consider for review in 2001 or 2002, as either a new listing in or
changing the current listing from reasonably anticipated to be a human
carcinogen to the known to be a human carcinogen category in the
Eleventh Report. These nominations are provided with their Chemical
Abstracts Services (CAS) Registry numbers (where available) and pending
review action. Additional nominations for the Eleventh Report or
modifications to the nominations in the attached table may be
identified and would be announced in future Federal Register notices.
The NTP solicits public input on these 16 nominations and asks for relevant
[[Page 38431]]
information concerning their carcinogenesis, as well as current
production data, use patterns, or human exposure information. The NTP
also invites interested parties to identify any scientific issues
related to the listing of a specific nomination in the RoC that they
feel should be addressed during the reviews. Comments concerning these
nominations for listing in or changing the current listing in the
Eleventh Report on Carcinogens will be accepted through September 24,
2001. Individuals submitting public comments are asked to include
relevant contact information (name, affiliation (if any), address,
telephone, fax, and email). Comments or questions should be directed to Dr. C.W. Jameson at the address listed above.
Additional Nominations for Delisting or Listing Encouraged
The NTP solicits and encourages the broadest participation from
interested individuals or parties in nominating agents, substances, or
mixtures for listing in or delisting from the Eleventh and future RoCs.
Nominations should contain a rationale for listing or delisting.
Appropriate background information and relevant data (e.g. Journal
articles, NTP Technical Reports, IARC listings, exposure surveys,
release inventories, etc.), which support a nomination, should be
provided or referenced when possible. Contact information for the
nominator should also be included (name, affiliation (if any), address,
telephone, fax, and email). Nominations should be sent to Dr. Jameson's attention at the address given above.
Dated: July 12, 2001.
Kenneth Olden,
Director, National Toxicology Program.
Summary for Agents, Substances, Mixtures or Exposure Circumstances to be Reviewed in 20012002 for Possible
Listing in the Report on Carcinogens, Eleventh Edition
Nomination to be reviewed/CAS No. Primary uses or exposures Nominated by Basis for nomination
1Amino2,4dibromoanthraquinone 1Amino2,4 NIEHS \1\............ Results of NTP Bioassay
(81492). dibromoanthraquinone is (TR 383, 1996) that
an anthraquinonederived reported clear evidence
vat dye that is used in of carcinogenicity at
the textile industry. multiple tumor sites in
multiple species of
experimental animals.
2Amino3,4dimethylimidazo[4,5 MeIQ is a heterocyclic NIEHS \1\............ IARC \2\ finding of
f]quinoline (MeIQ) (77094112). amine that is formed sufficient evidence of
during heating or cooking carcinogenicity in
and is found in cooked experimental animals
meat and fish. (Vol. 56; 1993).
Cobalt Sulfate (10026241)....... Cobalt sulfate is used in NIEHS \1\............ Results of NTP Bioassay
electroplating and (TR 471, 998) which
electrochemical reported clear evidence
industries. It is also of carcinogenic activity
used as a coloring agent in female F344/N rats
for ceramics, a drying and male and female
agent in inks, paints, B63F1 mice and some
varnishes and linoleum, evidence of carcinogenic
and has been added to activity in male F344/N
animal feed as a mineral rats. supplement.
Diazoaminobenzene (DAAB) (13635 DAAB is used as an NIEHS \1\............ Results of research
6). intermediate, complexing supported the by the NTP
agent, polymer additive that demonstrated this
and also to promote chemical is
adhesion of natural quantitatively
rubber to steel. metabolized to benzene
(a known human
carcinogen).
Diethanolamine (DEA) (111422)... DEA is used in the Dr. Franklin Mirer of Results of NTP Bioassay
preparation of the United Auto (TR 478, 1999) which
surfactants used in Workers. reported clear evidence
liquid laundry, of carcinogenic activity
dishwashing detergents, in male and female
cosmetics, shampoos, and B6C3F1 mice.
hair conditioners and in textile processing,
industrial gas
purification and as an anticorrosion agent.
Hepatitis B Virus (HBV)........... HBV is a small DNA NIEHS \1\............ IARC \2\ finding of
enveloped virus that is sufficient evidence of
transmitted by carcinogenicity in
percutaneous or humans (Vol. 59, 1994).
permuscosal exposure to
infectious blood or body
fluids that contain blood.
Hepatitis C Virus (HCV)........... HCV is an RNAenveloped NIEHS \1\............ IARC \2\ finding of
virus that is transmitted sufficient evidence of
mainly by percutaneous carcinogenicity in
exposure to infectious humans (Vol. 59, 1994). blood and less
efficiently by
permuscosal exposure to
infectious blood or body
fluids that contain blood.
High Risk Human Papillomaviruses HPVs are small, non NIEHS \1\............ IARC \2\ finding of
(HPVs). enveloped viruses that sufficient evidence of
infect the skin and oral carcinogenicity in
and genital mucosa. HPV humans (Vol. 70, 1997). infections are common
throughout the world.
XRadiation and GAMMA (
Neutrons.......................... Exposure to neutrons NIEHS \1\............ IARC \2\ finding of
normally occurs from a sufficient evidence of
mixed irradiation field carcinogenicity in
in which neutrons are a humans (Vol. 75, 2000). minor component. The
exceptions are exposure
of patients to neutron
radiotherapy beams and exposures of aircraft
passengers and crew.
Occupational exposure to lead or Major occupational NIEHS \1\............ Recent published data
lead compounds. exposures are in the lead that indicate an excess
smelting and refining of cancers in workers
industries, battery exposed to lead and lead
manufacturing plants, compounds.
steel welding or cutting
operations, construction, and firing ranges.
Naphthalene (91203)............. Naphthalene is used as an NIEHS \1\............ Results of NTP Bioassay
intermediate in the (TR 500, 2000) that
synthesis of many reported clear evidence
industrial chemicals, an of carcinogenicity in
ingredient in some moth male & female rats and
repellants and toilet some evidence in female
bowl deodorants, as an mice. antiseptics for
irrigating animal wounds
and to control lice on
livestock and poultry.
Nitrobenzene (98953)............ Nitrobenzene is used NIEHS \1\............ IARC \2\ finding
mainly in the production sufficient of evidence
of aniline, itself a of carcinogenicity in
major chemical experimental animals
intermediate in the (Vol. 65, 1996). production of dyes.
Nitromethane (75525)............ Nitromethane is used as an NIEHS \1\............ Results of NTP Bioassay
additive to many (TR 461, 1997) that
halogenated solvents and reported clear evidence
aerosol propellants as a of carcinogenicity in
stabilizer. It can also male & female mice and
be used in specialized clear evidence in female
fuels and in explosives. rats.
Phenylimidazopyridine [PhIP, PhIP is a heterocyclic Dr. Takashi Sugimura, Nomination based on Dr.
(105650235)]. amine that is formed President Emeritus, Sugimura's recent
during heating or cooking National Cancer reviews of the
and is found in cooked Center of Japan. carcinogenicity of
meat and fish. heterocyclic amines.
4,4'Thiodianiline (139651)..... 4,4'Thiodianiline has NIEHS \1\............ IARC \2\ finding of
been produced sufficient evidence of
commercially since the carcinogenicity in
early 1940's as an experimental animals
intermediate of several (Suppl 7, 1987). and
diazo dyes. result of NTP Bioassay
studies that
demonstrated clear
evidence of
carcinogenicity in mice
and rats (TR047, 1978).
\1\ The National Institute of Environmental Health Sciences (NIEHS). \2\ International Agency for Research on Cancer (IARC).
[FR Doc. 0118391 Filed 72301; 8:45 am]
BILLING CODE 414001P