National Toxicology Program: Chemicals nominated for toxicological studies; study recommendations; comment request,

[Federal Register: August 20, 2004 (Volume 69, Number 161)]

[Notices]

[Page 51691-51693]

From the Federal Register Online via GPO Access [wais.access.gpo.gov]

[DOCID:fr20au04-114]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

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)

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://ntp-server.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 non-animal models for mechanistic-based 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, 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.

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; e-mail: 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 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 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 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, Federal agencies represented on the ICCEC, the NTP Board of Scientific Counselors--an external scientific advisory body, the NTP Executive Committee--the 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 multi-step 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://ntp-server.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. n-Buityl glycidyl ether [2426- National

Suspicion of toxicity based Toxicological studies: 08-6].

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-(2-ethylhexyl)phthalate U.S. Food and Long-term risks associated Toxicological studies: Tiered (DEHP) [118-71-7].

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 non-human 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 non-DEHP-

subchronic intravenous containing products.

exposure to neonatal male rats and nonhuman primates. Ionic liquids 1-Butyl-3- University of Widespread interest as

Toxicological studies: methylimida zo lium chloride Alabama Center replacements for volatile --Toxicological [79917-90-1] 1-Butyl-1-

for Green

organic compounds (VOCs) in characterization methylpyrrolidinium chloride Manufacturing. various applications; lack --Coordinate research program [479500-35-1] N-

of toxicity data.

with the U.S. EPA. Butylpyridinium chloride [1124-64-7]. 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://ntp-server.niehs.nih.gov/ )

Stachybotrys chartarum [67892- Private

Public concern regarding Toxicological studies: 26-2].

Individual.

potential non-infectious --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 [1314-35-8] 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

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--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 [94-26-8]........ 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

dose-response of reproductive

male reproductive toxicant; lack of effects, and human adequate toxicity exposure. data. Decane [124-18-5]............. 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 [1120-21-4].......... 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. 04-19136 Filed 8-19-04; 8:45 am]

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