Federal Register: August 20, 2004 (Volume 69, Number 161)
DOCID: FR Doc 04-19136
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 Comment 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:
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 24, 2004, the ICCEC met to review 10 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 24, 2004 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. 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. 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 its meeting on June 24, 2004, the ICCEC reviewed 10 new nominations for NTP studies. For 7 of these nominations, the ICCEC recommended one or more types of toxicological studies, and for 3 nominations, the ICCEC deferred making specific study recommendations pending review of additional information. The nominated substances with Chemical Abstract Service (CAS) Registry numbers, nomination source, nomination rationale, and specific study recommendations are given in the accompanying tables.
The ICCEC is composed of representatives from the U.S. Consumer Product Safety Commission, U.S. Department of Defense, U.S. Environmental Protection Agency (U.S. EPA), U.S. Food and Drug Administration's National Center for Toxicological Research, National Center for Environmental Health/Agency for Toxic Substances and Disease Registry, National Institutes of Health's (NIH) National Cancer Institute, 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 mechanisticbased research, 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 October 19, 2004. 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.
Send comments or information to Dr. Scott A. Masten, Office of Chemical Nomination and Selection, NIEHS/NTP, P.O. 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 pharmacokinetics, 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,
Federal agencies represented on the ICCEC, the NTP Board of Scientific
Counselorsan external scientific advisory body, the NTP Executive Committeethe NTP Federal interagency policy body, and
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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 multistep evaluative process provides the NTP with
direction and guidance to ensure that its 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 its 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: August 10, 2004.
Samuel Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
Substances Nominated to the NTP for Toxicological Studies and
Recommendations Made by the NTP Interagency Committee for Chemical Evaluation and Coordination on June 24, 2004
Table 1.Substances Recommended for Study *
Recommendations for
Substance [CAS number] Nominated by Nomination rationale toxicological studies
Bitter orange extract [No CAS Private Consumer exposure through Toxicological studies:
No.]. Individual. increasing dietary Developmental toxicity
supplement use; suspicion of Physiological responses
toxicity; lack of adequate (e.g., cardiovascular and
toxicity data. cerebrovascular)
Subchronic toxicity
Toxicokinetics (of
constituents)
Studies alone and in
combination with caffeine
Studies in rats and possibly
miniature pigs.
nBuityl glycidyl ether [2426 National Suspicion of toxicity based Toxicological studies:
086]. Institute of on structural features; Toxicological
Environmental positive results in genetic characterization including
Health Sciences. toxicity studies; reproductive toxicity,
substantial potential for carcinogenicity, and analysis
human exposure and a lack of of urinary metabolites
chronic toxicity data. Coordinate with voluntary
data development activities of
the U.S. EPA.
Di(2ethylhexyl)phthalate U.S. Food and Longterm risks associated Toxicological studies: Tiered
(DEHP) [118717]. Drug with medical exposures of research programs to address:
Administration. infants have not been Quantitative studies of
clearly elucidated; toxicokinetics and
significant knowledge gaps biotransformation following
on the toxicokinetics and intravenous exposure in
effects in fetal and neonatal male nonhuman
neonatal primates of primates
intravenous exposure; Assessment of toxicokinetics,
further studies will better reproductive and immune
define risks and benefits of endpoints following acute and
utilizing nonDEHP subchronic intravenous
containing products. exposure to neonatal male rats
and nonhuman primates.
Ionic liquids 1Butyl3 University of Widespread interest as Toxicological studies:
methylimida zo lium chloride Alabama Center replacements for volatile Toxicological
[79917901] 1Butyl1 for Green organic compounds (VOCs) in characterization
methylpyrrolidinium chloride Manufacturing. various applications; lack Coordinate research program
[479500351] N of toxicity data. with the U.S. EPA. Butylpyridinium chloride
[1124647].
Perfluorinated compounds U.S. Presumed widespread human Toxicological studies:
class study [Mutliple CAS Environmental exposure; known toxicity of Tiered research program to
Nos.]. Protection certain class members; include pharmacokinetics,
Agency. insufficient information to mechanistic, reproductive
assess hazard/risk across toxicity, and carcinogenicity
entire structural class. studies (for specific
compounds, see supporting
document available at http://ntpserver.niehs.nih.gov/ )
Stachybotrys chartarum [67892 Private Public concern regarding Toxicological studies:
262]. Individual. potential noninfectious Toxicological
National adverse health effects of characterization including
Institute of fungal exposures in indoor immunotoxicity.
Environmental environments; inadequate
Health Sciences. toxicological data available
evaluating potential
systemic toxicity from long
term exposure to this
organism under relevant
exposure scenarios.
Tungsten trioxide [1314358] National Cancer Important industrial raw Toxicological studies:
and fibrous tungsten Institute. materials; one of several Toxicoligical
suboxides. metals that may form toxic characterization
fibrous ``whiskers''; Genotoxicity
carcinogenic potential of Characterize fiber stability
tungsten (vs. cemented and biopersistence
tungsten carbide) is not In vitro toxicity to lung
adequately characterized. cells
Comparative intratracheal
toxicity studies with a known
hazardous fiber [[Page 51693]]
Further studies including
carcinogenicity will be
considered following
completion of above.
* Note: A recommendation for ``toxicological characterization''
in this table includes studies for genotoxicity, subchronic
toxicity, and chronic toxicity/carcinogenicity, as determined to be
appropriate during the conceptualization and design of a research
program to address toxicological data needs. Though other types of
studies (e.g., metabolism, pharmacokinetics, immunotoxicity,
reproductive/developmental toxicity) may be conducted as part of a
complete toxicological characterization, these types of studies are not listed unless they were specifically recommended.
Table 2.Substance for Which Specific Study Recommendations Were Deferred
Rationale for
Substance [CAS number] Nominated by Nominated for Nomination rationale deferral/further
information needed
Butylparaben [94268]........ National Toxicological Widespread use in Further review of
Institute of characterization foods, cosmetics, data on estrogen
Environmental including and receptor binding,
Health Sciences. reproductive pharmaceuticals; pharmacokinetics,
toxicity studies. potential doseresponse of
reproductive male reproductive
toxicant; lack of effects, and human
adequate toxicity exposure.
data.
Decane [124185]............. National Cancer Carcinogenicity Widespread Review of industry
Institute. studies. industrial use and voluntary data
environmental development
occurrence as air activities
pollutant; coordinated by the
suspicion of U.S. EPA.
carcinogenicity but
no adequate
carcinogenicity
study available.
Undecane [1120214].......... National Cancer Carcinogenicity Widespread Review of industry
Institute. studies. industrial use and voluntary data
environmental development
occurrence as air activities
pollutant; coordinated by the
suspicion of U.S. EPA.
carcinogenicity but
no adequate
carcinogenicity
study available. [FR Doc. 0419136 Filed 81904; 8:45 am]
BILLING CODE 414001P
SUMMARY:
Chemicals nominated for toxicological studies; study recommendations; comment request,