National Toxicology Program (Ntp); Office of Chemical Nomination and Selection; Announcement of and Request for Public Comment on Toxicological Study Nominations to the NTP

Federal RegisterApr 11, 2006

71 Fed. Reg. 18341 (Apr. 11, 2006)

AGENCY:

National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health.

ACTION:

Notice; request for comments and additional information.

SUMMARY:

The 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. This notice (1) provides brief background information and study recommendations regarding 10 nominations for study by the NTP (Table 1), (2) solicits public comment on the nominations and study recommendations, and (3) requests the submission of additional relevant information for consideration by the NTP in its continued review of these nominations. An electronic copy of this announcement, supporting documents for each nomination, and further information on the NTP and the NTP Study Nomination and Review Process can be accessed through the NTP Web site ( http://ntp.niehs.nih.gov/;;; select “Nominations to the Testing Program”).

DATES:

Comments or information should be submitted by May 10, 2006.

ADDRESSES:

Correspondence should be addressed to Dr. Scott A. Masten, Director, Office of Chemical Nomination and Selection, NIEHS/NTP, 111 T.W. Alexander Drive, P. O. Box 12233, Research Triangle Park, North Carolina 27709; telephone: 919-541-5710; FAX: 919-541-3647; e-mail: masten@niehs.nih.gov.

SUPPLEMENTARY INFORMATION:

Background Information

The NTP actively seeks to identify and select for study chemicals and other substances 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. Nominations can be submitted to the NTP at http://ntp.niehs.nih.gov/ select “Nominations to the Testing Program” or by contacting Dr. Scott Masten (see ADDRESSES above). Substances considered appropriate for study generally fall into two broad yet overlapping categories: (1) Substances judged to have high concern as possible public health hazards 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 for evaluating dose-response relationships. Nominations are also solicited for 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 agents.

Study nominations may entail the evaluation of a variety of health-related effects including, but not limited to, reproductive and developmental toxicity, genetic toxicity, immunotoxicity, neurotoxicity, metabolism and disposition, and carcinogenicity in appropriate experimental models. In reviewing and selecting nominations for study, the NTP also considers legislative mandates that require responsible private sector 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.

Nominations undergo a multi-step, formal process of review. Briefly, during the entire nomination review and selection process, the NTP works with staff at other federal agencies and interested parties to supplement information about nominated substances and to ensure that regulatory and public health needs are addressed. The nomination review and selection process is accomplished through the participation of representatives from the NIEHS, other federal agencies represented on the Interagency Committee for Chemical Evaluation and Coordination (ICCEC), the NTP Board of Scientific Counselors (BSC)—an external scientific advisory body, the NTP Executive Committee—the NTP federal interagency policy body, and the public. Preliminary study recommendations for each nomination are developed and refined by the nominator, NTP staff, and the ICCEC. Preliminary study recommendation for the nominations may be refined as the formal review process continues. NTP also considers recommendations from the BSC and the NTP Executive Committee, public comments received on the nominations, and other available information in selecting candidate substances for study. The NTP initiates appropriate toxicology and carcinogenicity studies as time and resources permit.

The nomination review and selection process is described in further detail on the NTP Web site ( http://ntp.niehs.nih.gov/;;; select “Nominations to the Testing Program”).

Request for Comments and Additional Information

The NTP invites interested parties to submit written comments or supplementary information on the nominated substances and study recommendations that appear in Table 1. 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 interested in identifying appropriate animal and non-animal experimental models for mechanistic-based research, including genetically modified rodents and higher-throughput in vitro test methods, and as such, solicits comments regarding the use of specific in vivo and in vitro experimental approaches to address questions relevant to the nominated substances and issues under consideration. The BSC will discuss the nominations listed in Table 1 at a public meeting on June 13, 2006. A separate Federal Register notice will be published in the future about this meeting. Comments or additional information may be submitted at any time; however, to ensure adequate time for consideration prior to the June 13, 2006 BSC meeting, comments should be submitted by May 10, 2006. The NTP will not respond to submitted comments; however, all information received will be become part of the official record that the NTP considers in its ongoing review of these nominations. Persons submitting comments 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 publicly available electronically on the NTP website as they are received ( http://ntp.niehs.nih.gov/ select “Nominations to the Testing Program”).

Background Information on the NTP Office of Chemical Nomination and Selection

The NTP Office of Chemical Nomination and Selection (OCNS) manages the solicitation, receipt, and review of NTP toxicology study nominations. The OCNS conducts an initial review of each study nomination received to determine whether the substance or issue has been adequately studied or has been previously considered by the NTP. For nominations not eliminated from consideration or deferred at this stage, the OCNS initiates a formal review process, as described above. The OCNS also ensures adequate background information is available to support the review for each nomination and corresponds with interested parties regarding the status of NTP study nominations. For further information on the OCNS visit the NTP Web site ( http://ntp.niehs.nih.gov select “Nominations to the Testing Program”) or contact Dr. Masten (see ADDRESSES above).

Dated: March 28, 2006.

Samuel H. Wilson,

Deputy Director, National Institute of Environmental Health Sciences and National Toxicology Program.

Table 1.—Study Recommendations for Substances Nominated to the NTP for Toxicological Studies

Substance [CAS No.]	Nominated by	Nomination Rationale	Study Recommendations
Arbutin 497-76-7]	NIEHS	Consumer exposure through food, cosmetics, and dietary supplements; lack of adequate toxicological data; suspicion of toxicity based on chemical structure	—In vitro and in vivo metabolism and disposition studies. —In vitro and in vivo genotoxicity studies. —Emphasis on understanding gastrointestinal metabolism and disposition, identifying experimental animal model representative of humans, and development of appropriate biomarkers.
tert-Butylacrylamide [107-58-4]	NCI	High production volume (HPV); potential worker and consumer exposures; lack of adequate toxicological data; suspicion of toxicity based on chemical structure	—Metabolism and disposition studies. —Subchronic toxicity studies. —Mammalian genotoxicity studies. —Coordinate studies with voluntary data development activities of the Extended HPV (EHPV) Program.
Ceric oxide [1306-38-3]	NIEHS	Widespread industrial use and potential for increasing exposure; demonstrated pulmonary toxicity; lack of toxicity data for nanoscale form —Toxicological characterization including chemical disposition and toxicokinetics —Comparative inhalation toxicity studies of microscale and nanoscale forms —Dermal penetration studies
Diazonaphthoquinone derivatives Sodium 1,2-naphthoquinone-2-diazide-5-sulfonate [2657-00-3] 2,3,4-Trihydroxybenzophenone tris(1,2-naphthoquinonediazide-5-sulfonate) [5610-94-6] 2,3,4-Trihydroxybenzophenone 1,2-naphthoquinonediazide-5-sulfonate [68510-93-0]	NIEHS	Moderate production volume; potential worker exposures from production and use of photoresists; lack of adequate toxicological data	—In vitro toxicity studies evaluating genotoxicity, immunotoxicity and phototoxicity. —Dermal penetration studies.
3-Dimethylaminopropyl methacrylamide [5205-93-6]	NCI	High production volume (HPV); potential worker and consumer exposures; lack of adequate toxicological data; demonstrated toxicity in short-term studies	—Metabolism and disposition studies. —Genotoxicity studies. —Subchronic toxicity studies. —Coordinate studies with voluntary data development activities of the Extended HPV (EHPV) Program.
Flame retardants Antimony trioxide [1309-64-4] Decabromodiphenyl oxide [1163-19-5]	Consumer Product Safety Commission Staff	Anticipated increased use in upholstered furniture and bedding and potential consumer exposures from these uses; insufficient toxicity data to assess potential health risks	See specific chemicals below: —Chronic toxicity studies (oral route). —Consider studies of nanoscale form if used in or released during flame retardant applications. —Developmental neurotoxicity studies. —Studies only to be performed if adequate private sector study not identified or planned.
Tris (chloropropyl) phosphate, mixture of four isomers [13674-84-5; 76025-08-6; 76649-15-5; 6145-73-9]			—Subchronic and chronic toxicity studies (oral route). —Studies to focus on commercial mixture or major isomers present in commercially used mixtures.
Phosphonic acid, (3-((hydroxymethyl) amino)-3-oxopropyl)-, dimethyl ester [20120-33-6]			—Subchronic and chronic toxicity studies (oral route). —Dermal absorption studies.

Tris (hydroxymethyl) phosphine oxide [1067-12-5]			—Subchronic and chronic toxicity studies (oral route). —Dermal absorption studies.
Aromatic phosphates tert-Butylphenyl diphenyl phosphate [56803-37-3] 2-Ethylhexyl diphenyl phosphate [1241-94-7] Isodecyl diphenyl phosphate [29761-21-5] Phenol, isopropylated, phosphate (3:1) [68937-41-7] Tricresyl phosphate [1330-78-5] Triphenyl phosphate [115-86-6]			For one or more representative aromatic phosphates: —Subchronic and chronic toxicity studies (oral route). —Neurotoxicity and/or developmental neurotoxicity studies. —Coordinate with the U.S. Environmental Protection Agency to pursue additional testing by manufacturers.
Gypsum, natural and synthetic forms [13397-24-5]	Mount Sinai-Irving J. Selikoff Center for Occupational and Environmental Medicine Operative Plasterers' and Cement Masons' International Association of the United States and Canada	Widespread worker exposures in numerous occupations and to the general population after destruction of the World Trade Centers in 2001; limited toxicity data to assess potential health risks	—Short-term pulmonary toxicity studies. —Comparative studies of intratracheal versus inhalation routes of administration. —Studies are of relatively low priority given low suspicion of toxicity.
N-methyl-3-oxobutanamide [20306-75-6]	NCI	High production volume; potential worker and environmental exposures; lack of adequate toxicological data	—In vitro and in vivo genotoxicity studies. —Include structurally-related diketene compounds and N-phenyl derivatives.
Phenoxyethyl acrylate [48145-04-6]	NCI	High production volume; potential worker and consumer exposures; lack of adequate toxicological data	—Defer pending review of voluntary data submission through the Extended HPV (EHPV) Program.
Trifluoromethylbenzene [98-08-8]	NCI	High production volume and potential for increased use; potential worker exposures; lack of adequate toxicological data; demonstrated toxicity in short-term studies	Defer pending review of 1) production data through the 2006 Toxic Substances Control Act (TSCA) Inventory Update Rule, and 2) Organization for Economic Cooperation and Development (OECD) Screening Information Data Set (SIDS) program output.
National Institute of Environmental Health Sciences (NIEHS); National Cancer Institute (NCI)
The term “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. Other types of studies (e.g., metabolism and disposition, immunotoxicity, and reproductive and developmental toxicity) may be conducted as part of a complete toxicological characterization; however, these types of studies are not listed unless they are specifically recommended.

[FR Doc. E6-5217 Filed 4-10-06; 8:45 am]

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