[Federal Register Volume 68, Number 136 (Wednesday, July 16, 2003)]
[Notices]
[Pages 42068-42071]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-18010]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


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)

    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 non-animal 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, e-mail 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://ntp-server.niehs.nih.gov.
    Send comments or information to Dr. Scott A. Masten, Office of 
Chemical Nomination and Selection, NIEHS/NTP, PO Box 12233, MD A3-07, 
Research Triangle Park, North Carolina 27709; telephone: (919) 541-
5710; Fax: (919) 541-3647; e-mail: [email protected].

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 cross-species extrapolation or evaluating dose-response 
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 health-related 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 over-riding factor in the NTP's decision to study a particular 
substance.
    The review and selection of substances nominated for study is a 
multi-step 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 Counselors--an 
external scientific advisory body, the NTP Executive Committee--the 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 11329-11331). This multi-step 
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://ntp-server.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
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                                                                                           Recommendations for
         Substance  [CAS No.]                Nominated by         Nomination rationale    toxicological studies
----------------------------------------------------------------------------------------------------------------
Acrylamide [79-06-1] and Glycidamide   U.S. Food and Drug       Inadequate information   --Toxicological
 [5694-00-8].                           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 [1345-04-6]......  National Cancer          Significant human        Chronic toxicity/
                                        Institute..              exposure in              carcinogenicity.
                                                                 occupational settings
                                                                 and suspicion of
                                                                 carcinogenicity.
Cadmium telluride [1306-25-8]........  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 [8000-27-9]..  National Cancer          Widespread occupational  --Toxicological
                                        Institute.               and consumer exposure;   characterization.
                                                                 lack of basic           --Developmental
                                                                 toxicology data.         toxicity.
Chondroitin sulfate [9007-28-7]......  National Cancer          Widespread long-term     --Chronic toxicity/
                                        Institute.               use as a dietary         carcinogenicity.
                                                                 supplement and          --Carcinogenicity of
                                                                 inadequate data to       chondroitin sulfate
                                                                 assess safety.           and glucosamine
                                                                                          combined.
Dimethylethanolamine [108-01-0]......  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 pre-clinical
                                                                 safety assessment is
                                                                 needed.
Glucosamine [3416-24-8]..............  National Cancer          Widespread long-term     --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      --Size--and
                                        for Biological and       anticipated future       composition--dependent
                                        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]]

 
trans--Resveratrol [501-36-0]........  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 [79-94-7]......  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) [21850-44-2].     Environmental Health     little toxicity data     characterization.
                                        Sciences.                available; suspicion    --In vivo genotoxicity.
                                                                 of carcinogenic          --Metabolism.
                                                                 potential due to 2,3-   --Carcinogenicity.
                                                                 dibromo-1-propanol
                                                                 substructure.
Tungsten [7440-33-7].................  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
----------------------------------------------------------------------------------------------------------------
4-Phenylcyclohexene [4994-16-5].  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.
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[FR Doc. 03-18010 Filed 7-15-03; 8:45 am]
BILLING CODE 4140-01-P