Federal Register: July 16, 2003 (Volume 68, Number 136)
DOCID: FR Doc 03-18010
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
NOTICE: NOTICES
ACTION: National Toxicology Program:
SUBJECT CATEGORY:
National Toxicology Program; Announcement of and Request for Public Comments on Substances Nominated to the National Toxicology Program (NTP) for Toxicological Studies and Study Recommendations Made by the NTP Interagency Committee for Chemical Evaluation and Coordination (ICCEC)
DOCUMENT SUMMARY:
Summary: The National Toxicology Program (NTP) continuously solicits and accepts nominations for toxicological studies to be undertaken by the program. Nominations of substances of potential human health concern are received from Federal agencies, the public, and other interested parties. These nominations are subject to several levels of review before selections for testing are made and toxicological studies are designed and implemented. Evaluation by the NTP Interagency Committee for Chemical Evaluation and Coordination (ICCEC) is the initial external review step in the NTP's formal selection process for NTP study nominations. On June 10, 2003, the ICCEC met to review 14 new nominations and make study recommendations. This announcement (1) Provides brief background information regarding the substances nominated to the NTP for study, (2) presents the ICCEC's study recommendations from its June 10, 2003 meeting, (3) solicits public comment on the nominations and study recommendations, and (4) requests the submission of additional relevant information for consideration by the NTP in its continued evaluation of these nominations.
Review of Study Nominations
Evaluation by the ICCEC is the initial external step in the NTP's formal selection process for NTP study nominations. At it's meeting on June 10, 2003, the ICCEC reviewed 14 new nominations for NTP studies. For 13 of these nominations, the ICCEC recommended one or more types of toxicological studies, and for one nomination, no studies were recommended at this time. The nominated substances with CAS numbers, nomination source, nomination rationale, and specific study recommendations are given in the accompanying tables.
The ICCEC is composed of representatives from the Agency for Toxic Substances and Disease Registry,
[[Page 42069]]
U.S. Consumer Product Safety Commission, U.S. Department of Defense, U.S. Environmental Protection Agency, U.S. Food and Drug
Administration's National Center for Toxicological Research, National
Institutes of Health's (NIH) National Cancer Institute, National Center
for Environmental Health, NIH's National Institute of Environmental
Health Sciences (NIEHS), National Institute for Occupational Safety and
Health, NIH's National Library of Medicine, and the Occupational Safety
and Health Administration. The ICCEC meets once or twice annually to
evaluate groups of new study nominations and to make recommendations
with respect to both specific types of studies and testing priorities. Request for Public Comment
Interested parties are invited to submit written comments or supplementary information on the nominated substances and study recommendations that appear in the accompanying tables. The NTP welcomes toxicology and carcinogenesis study information from completed, ongoing, or anticipated studies, as well as information on current U.S. production levels, use or consumption patterns, human exposure, environmental occurrence, or public health concerns for any of the nominated substances. The NTP is also interested in identifying appropriate new animal and nonanimal models for mechanistic based research, including genetically modified rodents, and as such, solicits comments regarding the use of specific in vivo and in vitro experimental models to address scientific questions relevant to the nominated substances or issues under consideration. All information received will be considered by the NTP in its continued review of these nominations. Comments or information should be sent to Dr. Scott Masten (contact information below) by September 15, 2003. Persons responding to this request should include their name, affiliation, mailing address, phone, fax, email address and sponsoring organization (if any) with the submission. Written submissions will be made available electronically on the NTP Web site as they are received.
An electronic copy of this announcement, Internet links to electronic versions of supporting documents for each nomination, and further information on the NTP and the NTP Chemical Nomination and Selection Process can be accessed through the NTP Web site: http://ntpserver.niehs.nih.gov .
Send comments or information to Dr. Scott A. Masten, Office of Chemical Nomination and Selection, NIEHS/NTP, PO Box 12233, MD A307, Research Triangle Park, North Carolina 27709; telephone: (919) 541 5710; Fax: (919) 5413647; email: masten@niehs.nih.gov. Background
The NTP actively seeks to identify and select for study chemicals and other agents for which sufficient information is not available to adequately evaluate potential human health hazards. The NTP accomplishes this goal through a formal open nomination and selection process. Substances considered appropriate for study generally fall into two broad yet overlapping categories: (1) Substances judged to have high concern as a possible public health hazard based on the extent of human exposure and/or suspicion of toxicity and (2) substances for which toxicological data gaps exist and additional studies would aid in assessing potential human health risks, e.g. by facilitating crossspecies extrapolation or evaluating doseresponse relationships. Input is also solicited regarding the nomination of studies that permit the testing of hypotheses to enhance the predictive ability of future NTP studies, address mechanisms of toxicity, or fill significant gaps in the knowledge of the toxicity of classes of chemical, biological, or physical substances. Substances may be studied to evaluate a variety of healthrelated effects, including but not limited to reproductive and developmental toxicity, genotoxicity, immunotoxicity, neurotoxicity, metabolism and disposition, and carcinogenicity. In reviewing and selecting nominated substances, the NTP also considers legislative mandates that require responsible private sector commercial organizations to evaluate their products for health and environmental effects. The possible human health consequences of anticipated or known human exposure, however, remain the overriding factor in the NTP's decision to study a particular substance.
The review and selection of substances nominated for study is a multistep process. A broad range of concerns are addressed during this process through the participation of representatives from the NIEHS, other Federal agencies, the NTP Board of Scientific Counselorsan external scientific advisory body, the NTP Executive Committeethe NTP Federal interagency policy body, and the public. This process is described in further detail in a March 2, 2000 Federal Register announcement (Volume 65, Number 42, pages 1132911331). This multistep evaluative process provides the NTP with direction and guidance to ensure that it's testing program addresses toxicological concerns relative to all areas of public health, and furthermore, that there is balance among the types of substances selected for study (e.g., industrial chemicals, consumer products, therapeutic agents). As such, it should be recognized that at any given time, the new study nominations under consideration do not necessarily reflect the overall balance of substances historically or currently being evaluated by the NTP in it's toxicology testing program. For further information on NTP toxicology studies (previous or in progress) visit the NTP Web site at http://ntpserver.niehs.nih.gov.
Dated: July 7, 2003.
Samuel Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
Substances Nominated to the NTP for Toxicological Studies and Recommendations Made by the ICCEC on June 10, 2003
[[Page 42070]]
Table 1.Substances Recommended for Study
Recommendations for
Substance [CAS No.] Nominated by Nomination rationale toxicological studies
Acrylamide [79061] and Glycidamide U.S. Food and Drug Inadequate information Toxicological
[5694008]. Administration. available to characterization.
accurately assess Toxicokinetics.
human health risks Mechanistic
from exposure to (hemoglobin adducts).
acrylamide in Carcinogenicity.
foodstuffs; a properly Bioavailability from
designed well food and drinking
conducted, GLP water.
compliant bioassay
with appropriate
ancillary studies is
needed to provide dose
response information
and account for the
food matrix through
which humans are
exposed.
Antimony trisulfide [1345046]...... National Cancer Significant human Chronic toxicity/
Institute.. exposure in carcinogenicity.
occupational settings
and suspicion of
carcinogenicity.
Cadmium telluride [1306258]........ U.S. Department of Potential for Toxicological
Energy, Brookhaven widespread characterization.
National Laboratory, applications in Chemical disposition
National Renewable photovoltaic energy (oral and inhalation
Energy Laboratory, generation; routes).
First Solar, Inc. anticipated increase
in human exposures;
further data needed to
address health and
safety issues related
to manufacture and use.
Cedarwood oil, Virginia [8000279].. National Cancer Widespread occupational Toxicological
Institute. and consumer exposure; characterization.
lack of basic Developmental
toxicology data. toxicity.
Chondroitin sulfate [9007287]...... National Cancer Widespread longterm Chronic toxicity/
Institute. use as a dietary carcinogenicity.
supplement and Carcinogenicity of
inadequate data to chondroitin sulfate
assess safety. and glucosamine
combined.
Dimethylethanolamine [108010]...... National Institute of Potential for Metabolism.
Environmental Health widespread human
Sciences. exposure through its
use in industrial and
consumer products;
inadequate
toxicological
database; some
ethanolamines can
interfere with choline
uptake and utilization
and may also generate
nitrosamines.
Drugs positive for QT Interval U.S. Food and Drug QT interval Initiate a study
Prolongation/Induction of Torsade Administration. prolongation and program to develop in
Proarrhythmia [No CAS No.]. torsade de pointes is vitro and in vivo test
a high priority cause systems for assessing
for concern in drug QT interval
development and prolongation.
regulatory safety
evaluation; a clear
definition of the
strengths,
limitations, and
future performance
characteristics of the
canine telemetry model
for preclinical
safety assessment is
needed.
Glucosamine [3416248].............. National Cancer Widespread longterm Chronic toxicity/
Institute. use as a dietary carcinogenicity.
supplement and Carcinogenicity of
inadequate data to chondroitin sulfate
assess safety. and glucosamine
combined.
Nanoscale materials. [No CAS No.].... Rice University Center Intense current and Sizeand
for Biological and anticipated future compositiondependent
Environmental research and biological disposition
Nanotechnology. development focus; of nanocrystalline
further studies and fluorescent
development of semiconductor
appropriate materials.
toxicological methods Toxicological
are needed to characterization of
adequately assess high aspect ratio
health effects. carbon nanomaterials.
Role of particle core
and surface
composition in the
immunotoxicity of the
above listed
materials.
Phototoxicity of
representative metal
oxide nanoparticles. [[Page 42071]]
transResveratrol [501360]........ National Institute of Widespread human Toxicological
Environmental Health exposure from natural characterization.
Sciences. dietary sources and Carcinogenicity.
use of dietary Reproductive
supplements; suspicion toxicity.
of toxicity based on
estrogenic and
genotoxic activity;
insufficient data
available to
characterize safety.
Tetrabromobisphenol A [79947]...... National Institute of High production volume; Toxicological
Environmental Health widespread human characterization.
Sciences. exposure and suspicion Neurodevelopmental
of thyroid toxicity/ toxicity.
tumorigenicity. Carcinogencity.
Tetrabromobisphenol A bis(2,3 National Institute of High production volume; Toxicological
dibromopropyl ether) [21850442]. Environmental Health little toxicity data characterization.
Sciences. available; suspicion In vivo genotoxicity.
of carcinogenic Metabolism.
potential due to 2,3 Carcinogenicity.
dibromo1propanol
substructure.
Tungsten [7440337]................. National Center for Important industrial Toxicological
Environmental Health. materials; characterization.
insufficient data to Carcinogenicity.
assess human health Studies should focus
implications of on a representative
elevated urinary soluble tungsten
tungsten levels. compound.
Table 2.Substance for Which No Study Is Recommended at This Time
Rationale for
Nomination recommending no
Substance [CAS No.] Nominated by Nominated for rationale toxicological
studies
4Phenylcyclohexene [4994165]. Private Toxicological Present in indoor Low suspicion of
Individuals. characterization environments hazard based on
including primarily from available human
genotoxicity and carpet emissions; exposure and
neurotoxicity. concern that it toxicity
has not been information.
adequately tested
for potential
health effects. [FR Doc. 0318010 Filed 71503; 8:45 am]
BILLING CODE 414001P
SUMMARY:
Chemicals nominated for toxicological studies; study recommendations,
DOCUMENT BODY 2:
Summary: The National Toxicology Program (NTP) continuously solicits and accepts nominations for toxicological studies to be undertaken by the program. Nominations of substances of potential human health concern are received from Federal agencies, the public, and other interested parties. These nominations are subject to several levels of review before selections for testing are made and toxicological studies are designed and implemented. Evaluation by the NTP Interagency Committee for Chemical Evaluation and Coordination (ICCEC) is the initial external review step in the NTP's formal selection process for NTP study nominations. On June 10, 2003, the ICCEC met to review 14 new nominations and make study recommendations. This announcement (1) Provides brief background information regarding the substances nominated to the NTP for study, (2) presents the ICCEC's study recommendations from its June 10, 2003 meeting, (3) solicits public comment on the nominations and study recommendations, and (4) requests the submission of additional relevant information for consideration by the NTP in its continued evaluation of these nominations.
Review of Study Nominations
Evaluation by the ICCEC is the initial external step in the NTP's formal selection process for NTP study nominations. At it's meeting on June 10, 2003, the ICCEC reviewed 14 new nominations for NTP studies. For 13 of these nominations, the ICCEC recommended one or more types of toxicological studies, and for one nomination, no studies were recommended at this time. The nominated substances with CAS numbers, nomination source, nomination rationale, and specific study recommendations are given in the accompanying tables.
The ICCEC is composed of representatives from the Agency for Toxic Substances and Disease Registry,
[[Page 42069]]
U.S. Consumer Product Safety Commission, U.S. Department of Defense, U.S. Environmental Protection Agency, U.S. Food and Drug
Administration's National Center for Toxicological Research, National
Institutes of Health's (NIH) National Cancer Institute, National Center
for Environmental Health, NIH's National Institute of Environmental
Health Sciences (NIEHS), National Institute for Occupational Safety and
Health, NIH's National Library of Medicine, and the Occupational Safety
and Health Administration. The ICCEC meets once or twice annually to
evaluate groups of new study nominations and to make recommendations
with respect to both specific types of studies and testing priorities. Request for Public Comment
Interested parties are invited to submit written comments or supplementary information on the nominated substances and study recommendations that appear in the accompanying tables. The NTP welcomes toxicology and carcinogenesis study information from completed, ongoing, or anticipated studies, as well as information on current U.S. production levels, use or consumption patterns, human exposure, environmental occurrence, or public health concerns for any of the nominated substances. The NTP is also interested in identifying appropriate new animal and nonanimal models for mechanistic based research, including genetically modified rodents, and as such, solicits comments regarding the use of specific in vivo and in vitro experimental models to address scientific questions relevant to the nominated substances or issues under consideration. All information received will be considered by the NTP in its continued review of these nominations. Comments or information should be sent to Dr. Scott Masten (contact information below) by September 15, 2003. Persons responding to this request should include their name, affiliation, mailing address, phone, fax, email address and sponsoring organization (if any) with the submission. Written submissions will be made available electronically on the NTP Web site as they are received.
An electronic copy of this announcement, Internet links to electronic versions of supporting documents for each nomination, and further information on the NTP and the NTP Chemical Nomination and Selection Process can be accessed through the NTP Web site: http://ntpserver.niehs.nih.gov .
Send comments or information to Dr. Scott A. Masten, Office of Chemical Nomination and Selection, NIEHS/NTP, PO Box 12233, MD A307, Research Triangle Park, North Carolina 27709; telephone: (919) 541 5710; Fax: (919) 5413647; email: masten@niehs.nih.gov. Background
The NTP actively seeks to identify and select for study chemicals and other agents for which sufficient information is not available to adequately evaluate potential human health hazards. The NTP accomplishes this goal through a formal open nomination and selection process. Substances considered appropriate for study generally fall into two broad yet overlapping categories: (1) Substances judged to have high concern as a possible public health hazard based on the extent of human exposure and/or suspicion of toxicity and (2) substances for which toxicological data gaps exist and additional studies would aid in assessing potential human health risks, e.g. by facilitating crossspecies extrapolation or evaluating doseresponse relationships. Input is also solicited regarding the nomination of studies that permit the testing of hypotheses to enhance the predictive ability of future NTP studies, address mechanisms of toxicity, or fill significant gaps in the knowledge of the toxicity of classes of chemical, biological, or physical substances. Substances may be studied to evaluate a variety of healthrelated effects, including but not limited to reproductive and developmental toxicity, genotoxicity, immunotoxicity, neurotoxicity, metabolism and disposition, and carcinogenicity. In reviewing and selecting nominated substances, the NTP also considers legislative mandates that require responsible private sector commercial organizations to evaluate their products for health and environmental effects. The possible human health consequences of anticipated or known human exposure, however, remain the overriding factor in the NTP's decision to study a particular substance.
The review and selection of substances nominated for study is a multistep process. A broad range of concerns are addressed during this process through the participation of representatives from the NIEHS, other Federal agencies, the NTP Board of Scientific Counselorsan external scientific advisory body, the NTP Executive Committeethe NTP Federal interagency policy body, and the public. This process is described in further detail in a March 2, 2000 Federal Register announcement (Volume 65, Number 42, pages 1132911331). This multistep evaluative process provides the NTP with direction and guidance to ensure that it's testing program addresses toxicological concerns relative to all areas of public health, and furthermore, that there is balance among the types of substances selected for study (e.g., industrial chemicals, consumer products, therapeutic agents). As such, it should be recognized that at any given time, the new study nominations under consideration do not necessarily reflect the overall balance of substances historically or currently being evaluated by the NTP in it's toxicology testing program. For further information on NTP toxicology studies (previous or in progress) visit the NTP Web site at http://ntpserver.niehs.nih.gov.
Dated: July 7, 2003.
Samuel Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
Substances Nominated to the NTP for Toxicological Studies and Recommendations Made by the ICCEC on June 10, 2003
[[Page 42070]]
Table 1.Substances Recommended for Study
Recommendations for
Substance [CAS No.] Nominated by Nomination rationale toxicological studies
Acrylamide [79061] and Glycidamide U.S. Food and Drug Inadequate information Toxicological
[5694008]. Administration. available to characterization.
accurately assess Toxicokinetics.
human health risks Mechanistic
from exposure to (hemoglobin adducts).
acrylamide in Carcinogenicity.
foodstuffs; a properly Bioavailability from
designed well food and drinking
conducted, GLP water.
compliant bioassay
with appropriate
ancillary studies is
needed to provide dose
response information
and account for the
food matrix through
which humans are
exposed.
Antimony trisulfide [1345046]...... National Cancer Significant human Chronic toxicity/
Institute.. exposure in carcinogenicity.
occupational settings
and suspicion of
carcinogenicity.
Cadmium telluride [1306258]........ U.S. Department of Potential for Toxicological
Energy, Brookhaven widespread characterization.
National Laboratory, applications in Chemical disposition
National Renewable photovoltaic energy (oral and inhalation
Energy Laboratory, generation; routes).
First Solar, Inc. anticipated increase
in human exposures;
further data needed to
address health and
safety issues related
to manufacture and use.
Cedarwood oil, Virginia [8000279].. National Cancer Widespread occupational Toxicological
Institute. and consumer exposure; characterization.
lack of basic Developmental
toxicology data. toxicity.
Chondroitin sulfate [9007287]...... National Cancer Widespread longterm Chronic toxicity/
Institute. use as a dietary carcinogenicity.
supplement and Carcinogenicity of
inadequate data to chondroitin sulfate
assess safety. and glucosamine
combined.
Dimethylethanolamine [108010]...... National Institute of Potential for Metabolism.
Environmental Health widespread human
Sciences. exposure through its
use in industrial and
consumer products;
inadequate
toxicological
database; some
ethanolamines can
interfere with choline
uptake and utilization
and may also generate
nitrosamines.
Drugs positive for QT Interval U.S. Food and Drug QT interval Initiate a study
Prolongation/Induction of Torsade Administration. prolongation and program to develop in
Proarrhythmia [No CAS No.]. torsade de pointes is vitro and in vivo test
a high priority cause systems for assessing
for concern in drug QT interval
development and prolongation.
regulatory safety
evaluation; a clear
definition of the
strengths,
limitations, and
future performance
characteristics of the
canine telemetry model
for preclinical
safety assessment is
needed.
Glucosamine [3416248].............. National Cancer Widespread longterm Chronic toxicity/
Institute. use as a dietary carcinogenicity.
supplement and Carcinogenicity of
inadequate data to chondroitin sulfate
assess safety. and glucosamine
combined.
Nanoscale materials. [No CAS No.].... Rice University Center Intense current and Sizeand
for Biological and anticipated future compositiondependent
Environmental research and biological disposition
Nanotechnology. development focus; of nanocrystalline
further studies and fluorescent
development of semiconductor
appropriate materials.
toxicological methods Toxicological
are needed to characterization of
adequately assess high aspect ratio
health effects. carbon nanomaterials.
Role of particle core
and surface
composition in the
immunotoxicity of the
above listed
materials.
Phototoxicity of
representative metal
oxide nanoparticles. [[Page 42071]]
transResveratrol [501360]........ National Institute of Widespread human Toxicological
Environmental Health exposure from natural characterization.
Sciences. dietary sources and Carcinogenicity.
use of dietary Reproductive
supplements; suspicion toxicity.
of toxicity based on
estrogenic and
genotoxic activity;
insufficient data
available to
characterize safety.
Tetrabromobisphenol A [79947]...... National Institute of High production volume; Toxicological
Environmental Health widespread human characterization.
Sciences. exposure and suspicion Neurodevelopmental
of thyroid toxicity/ toxicity.
tumorigenicity. Carcinogencity.
Tetrabromobisphenol A bis(2,3 National Institute of High production volume; Toxicological
dibromopropyl ether) [21850442]. Environmental Health little toxicity data characterization.
Sciences. available; suspicion In vivo genotoxicity.
of carcinogenic Metabolism.
potential due to 2,3 Carcinogenicity.
dibromo1propanol
substructure.
Tungsten [7440337]................. National Center for Important industrial Toxicological
Environmental Health. materials; characterization.
insufficient data to Carcinogenicity.
assess human health Studies should focus
implications of on a representative
elevated urinary soluble tungsten
tungsten levels. compound.
Table 2.Substance for Which No Study Is Recommended at This Time
Rationale for
Nomination recommending no
Substance [CAS No.] Nominated by Nominated for rationale toxicological
studies
4Phenylcyclohexene [4994165]. Private Toxicological Present in indoor Low suspicion of
Individuals. characterization environments hazard based on
including primarily from available human
genotoxicity and carpet emissions; exposure and
neurotoxicity. concern that it toxicity
has not been information.
adequately tested
for potential
health effects. [FR Doc. 0318010 Filed 71503; 8:45 am]
BILLING CODE 414001P