[Federal Register Volume 67, Number 113 (Wednesday, June 12, 2002)]
[Notices]
[Pages 40329-40333]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-14821]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service


National Toxicology Program (NTP)

    Announcement of and Request for Public Comments on Substances 
Nominated to the National Toxicology Program (NTP) for Toxicological 
Studies and on Study Recommendations Made by the NTP Interagency 
Committee for Chemical Evaluation and Coordination (ICCEC)

Summary

    The NTP continuously solicits and accepts nominations for 
toxicological

[[Page 40330]]

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 undergo several 
levels of review before selections for testing are made and 
toxicological studies are designed and implemented. Evaluation by the 
NTP ICCEC is the initial external review step in the NTP's formal 
selection process for NTP study nominations. On April 17, 2002 the 
ICCEC met to review 19 new nominations and make study recommendations. 
This announcement (1) provides brief background information regarding 
the substances nominated to NTP for study, (2) presents the ICCEC's 
study recommendations from its April 17, 2002 meeting, (3) solicits 
public comment on the nominations themselves and on the study 
recommendations by the ICCEC, 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

    At it's meeting on April 17, 2002, the ICCEC reviewed 19 new 
nominations for NTP studies. For 14 of these nominations, one or more 
types of toxicological studies were recommended, and for 5 nominations, 
no studies were recommended at this time. The nominated substances with 
CAS numbers, nomination source, nomination rationale, specific study 
recommendations, and other pertinent information are given in the 
attached tables.
    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. The ICCEC is 
composed of representatives from the Agency for Toxic Substances and 
Disease Registry, U.S. Consumer Product Safety Commission, Department 
of Defense, U.S. Environmental Protection Agency, U.S. Food and Drug 
Administration's National Center for Toxicological Research, National 
Cancer Institute, National Center for Environmental Health, National 
Institute of Environmental Health Sciences, National Institute for 
Occupational Safety and Health, 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 Comments

    Interested parties are invited to submit comments or supplementary 
information on the nominated substances and study recommendations that 
appear in the attached tables. The NTP welcomes toxicology and 
carcinogenesis information from completed, ongoing, or planned studies, 
as well as information on current production levels, use 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 models for mechanistic based 
research, including transgenic or knockout mice, and welcomes comments 
regarding the use of specific animal models to address scientific 
questions relevant to the nominated substances and studies 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 by August 12, 2002. 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's 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, P. O. Box 12233, MD A3-
07, Research Triangle Park, North Carolina 27709; telephone: (919) 541-
5710; FAX: (919) 541-3647; email: [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) Those substances of 
greatest concern for public health 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 National 
Institute of Environmental Health Sciences, 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 testing program. For 
further information on NTP toxicology studies (previous or in progress) 
visit

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the NTP web site at http://ntp-server.niehs.nih.gov.

    Dated: June 5, 2002.
Samuel Wilson,
Deputy Director, National Toxicology Program.

Attachment

Substances Nominated to the NTP for Toxicological Studies and 
Recommendations Made by the ICCEC on April 17, 2002

                                   Table 1.--Substances Recommended for Study
----------------------------------------------------------------------------------------------------------------
                                                                 Nomination rationale;     Recommendations for
         Substance [CAS No.]                 Nominated by          other information      toxicological studies
----------------------------------------------------------------------------------------------------------------
Abrasive blasting agents; Coal slag;   National Institute for   High production volume   --Chronic inhalation
 Crushed glass; Garnet; Sand;           Occupational Safety      and widespread           toxicity in male rats;
 Specular hematite; Steel grit.         and Health;              occupational exposure;  --Pulmonary tissue
                                        Occupational Safety      lack of adequate         burden analysis.
                                        and Health               health effects
                                        Administration.          information; data
                                                                 needed to establish
                                                                 safe exposure limits.
5-Amino-o-cresol [2835-95-2].........  National Cancer          Widely used in           --Metabolism;
                                        Institute.               permanent hair dyes;    --Developmental and
                                                                 some evidence of         reproductive toxicity;
                                                                 toxicity; lack of       --Carcinogenicity.
                                                                 carcinogenicity data.
tert-Butyl hydroperoxide [75-91-2]...  National Cancer          High production volume   --Carcinogenicity;
                                        Institute.               industrial chemical;    --Consider mechanistic
                                                                 evidence for             studies related to
                                                                 genotoxicity and tumor   carcinogenicity of
                                                                 promotion activity;      organic peroxides as a
                                                                 lack of                  class.
                                                                 carcinogenicity data.
Chloramine-T [127-65-1] and p-         Private Individual.....  Investigational new      --In vitro and in vivo
 Toluenesulfonamide [70-55-3].                                   animal drug for          genotoxicity;
                                                                 antimicrobial use in    --Subchronic toxicity;
                                                                 aquaculture; evidence    and/or carcinogenicity
                                                                 for toxicity further     studies may be
                                                                 studies needed to        considered when
                                                                 establish safe residue   results of
                                                                 levels.                  genotoxicity studies
                                                                                          are available for
                                                                                          review.
Cobalt metal dust [7440-48-4]........  Cobalt Development       Widespread occupational  --Toxicological
                                        Institute;               exposure; evidence for   characterization
                                        International Union,     toxicity; insufficient   including
                                        United Auto Workers;     data to assess chronic   carcinogenicity and
                                        Occupational Safety      toxicity and             developmental toxicity
                                        and Health               carcinogenic potential.  (inhalation studies).
                                        Administration.
Ephedrine alkaloid dietary             National Cancer          Widely used dietary      --Developmental and
 supplements [no CAS No.].              Institute; National      supplement; reports of   reproductive toxicity;
                                        Institutes of Health     adverse effects in      --Subchronic toxicity;
                                        Office of Dietary        consumers; lack of      --Special emphasis on
                                        Supplements.             adequate toxicological   assessment of
                                                                 information for multi-   potential
                                                                 component dietary        cardiovascular and
                                                                 supplement               central ervous systems
                                                                 formulations.            effects;
                                                                                         --Studies should use
                                                                                          commercial ephedra
                                                                                          products with and
                                                                                          without caffeine and
                                                                                          other additives.
Ethanone, 1-(1,2,3,4,5,6,7,8-          Private Individual.....  High production volume   --Toxicological
 octahydro-2,3,8,8-tetramethyl-2-                                fragrance material;      characterization
 naphthalenyl)-(Iso-E Super) [54464-                             widespread consumer      including
 57-2].                                                          exposure; lack of        genotoxicity.
                                                                 toxicity data.
Hexafluorosilicic acid [16961-83-4]    Private Individuals      Primary agents used to   --Chemical
 and Sodium hexafluorosilicate [16893-  (multiple nominations).  fluoridate public        characterization
 85-9].                                                          drinking water           studies to assess
                                                                 systems; lack of         chemical fate under
                                                                 toxicity information;    aqueous conditions;
                                                                 assumed complete        --Toxicological studies
                                                                 dissociation to free     may be considered when
                                                                 fluoride under normal    results of chemical
                                                                 conditions of use not    characterization
                                                                 supported by             studies are available
                                                                 experimental evidence.   for review.
Ketamine hydrochloride [1867-66-9]...  U.S. Food and Drug       Approved drug for        --Comprehensive
                                        Administration.          anesthetic use in        neurotoxicity
                                                                 adults; off-label        assessment and
                                                                 pediatric use thought    toxicokinetics in
                                                                 to occur; causes         developing (post-
                                                                 severe lesions in        natal) non-human
                                                                 developing rat brain;    primates.
                                                                 further studies needed
                                                                 to assess safety of
                                                                 pediatric use.

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Mercury, ((o-carboxyphenyl)thio)ethyl- U.S. Food and Drug       Organomercurial          --Toxicokinetics;
 ,sodium salt (Thimerosal) [54-64-8].   Administration.          preservative widely     --Neurodevelopmental
                                                                 used in vaccines and     toxicity;
                                                                 other therapeutics;     --Comparative studies
                                                                 large exposed            with ethylmercury and
                                                                 population;              methylmercury under
                                                                 insufficient toxicity    different dosing
                                                                 data.                    regimens in non-human
                                                                                          primates;
                                                                                         --Coordinate with
                                                                                          ongoing federally-
                                                                                          sponsored research
                                                                                          efforts.
Nitrogen trifluoride [7783-54-2].....  National Cancer          Rapidly increasing       --Genotoxicity;
                                        Institute.               industrial demand;      --Metabolism.
                                                                 acute toxic effects
                                                                 well described;
                                                                 potential for toxicity
                                                                 based on oxidizing
                                                                 properties.
Sodium metasilicate [6834-92-0]......  National Institute for   Widespread occupational  --Subchronic toxicity
                                        Occupational Safety      exposure; evidence for   (inhalation studies);
                                        and Health.              biological activity;     -Respiratory
                                                                 insufficient toxicity    hypersensitivity.
                                                                 data.
Turpentine [8006-64-2]...............  International Union,     Widespread occupational  --Chronic toxicity;
                                        United Auto Workers.     and consumer exposure;  --Carcinogenicity.
                                                                 reports of kidney
                                                                 toxicity in exposed
                                                                 humans; insufficient
                                                                 chronic toxicity
                                                                 information.
Welding fume: Gas metal arc welding    National Institute for   Widespread Occupational  --Acute and subchronic
 with stainless steel electrode; Gas    Occupational Safety      exposure; evidence for   inhalation exposure
 metal arc welding with mild steel      and Health;              toxicity of mixture      studies to assess
 electrode; Manual arc welding with     International Union;     and components; gaps     neurotoxicity,
 stainless steel electrode.             United Auto Workers.     in available health      immunotoxicity, and
                                                                 effects data.            pulmonary toxicity of
                                                                                          all 3 welding fume
                                                                                          types;
                                                                                         --Chronic inhalation
                                                                                          toxicity and
                                                                                          carcinogenicity
                                                                                          studies with one or
                                                                                          more welding fume
                                                                                          types.
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                       Table 2.--Substances for Which No Study Is Recommended at This Time
----------------------------------------------------------------------------------------------------------------
                                                                                                 Rationale for
                                                                              Nomination        recommending no
       Substance [CAS No.]           Nominated by        Nominated for     rationale; other      toxicological
                                                                              information           studies
----------------------------------------------------------------------------------------------------------------
Hexachloro-1,3-butadiene [87-68-  Carcinogen          --Carcinogenicity   Persistent          Low commercial
 3].                               Identification      (at doses           industrial by-      production
                                   Committee           intermediate to     product widely      volume,
                                   (Advisory Body      those used in       dispersed in        insufficient
                                   for California      previous studies).  environment; some   evidence of
                                   Environmental                           evidence for        significant human
                                   Protection                              carcinogenicity;    exposure, and
                                   Agency).                                existing data       availability of
                                                                           insufficient to     adequate
                                                                           characterize        toxicological
                                                                           carcinogenic        data.
                                                                           hazard.
Infrasound [no CAS No.].........  National Institute  --Toxicological     Low frequency       Insufficient
                                   of Environmental    characterization.   sound ubiquitous    information on
                                   Health Sciences.                        in occupational     human exposures
                                                                           and community       in community
                                                                           settings;           settings and
                                                                           insufficient        questionable
                                                                           settings;           utility of
                                                                           insufficient data   additional
                                                                           to address public   studies in
                                                                           concerns            available animal
                                                                           regarding           models/test
                                                                           potential health    systems; Consider
                                                                           hazards at low      seeking
                                                                           exposure levels.    additional expert
                                                                                               opinion on human
                                                                                               exposure and
                                                                                               toxicity data
                                                                                               needs.
Magnesium oxide [1309-48-4].....  National Cancer     --Biological        High production     Adequate available
                                   Institute.          disposition.        volume industrial   toxicological
                                                      --Chronic            chemical;           data.
                                                       inhalation          widespread
                                                       toxicity.           occupational
                                                                           exposure; lack of
                                                                           chronic
                                                                           inhalation
                                                                           toxicity data.
Methylolurea [1000-82-4]........  National Institute  --Toxicological     High production     Inclusion in the
                                   of Environmental    characterization.   volume industrial   High Production
                                   Health Sciences.                        chemical;           Volume Chemical
                                                                           widespread use      Challenge
                                                                           and potential for   Program.
                                                                           human exposure;
                                                                           lack of toxicity
                                                                           information.

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4-Methylquinoline [491-35-0]....  Carcinogen          --Comparative       Ubiquitous          Low commercial
                                   Identification      metabolism          environmental       production
                                   Committee           studies (with       contaminant; some   volume,
                                   (Advisory Body      quinoline).         evidence for        insufficient
                                   for California     --Carcinogenicity.   carcinogenicity;    evidence of
                                   Environmental                           existing data       significant human
                                   Protection                              insufficient to     exposure, and
                                   Agency).                                characterize        availability of
                                                                           carcinogenic        adequate
                                                                           hazard.             toxicological
                                                                                               data.
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[FR Doc. 02-14821 Filed 6-11-02; 8:45 am]
BILLING CODE 4140-01-P