E8-23181. National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board of Scientific Counselors

AGENCY:

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

ACTION:

Meeting announcement and request for comments.

SUMMARY:

Pursuant to Public Law 92-463, notice is hereby given of a meeting of the NTP Board of Scientific Counselors (NTP BSC). The NTP BSC is a federally chartered, external advisory group composed of scientists from the public and private sectors that provides primary scientific oversight to the NTP Director and evaluates the scientific merit of the NTP's intramural and collaborative programs.

DATES:

The NTP BSC meeting will be held on November 20-21, 2008. The deadline for submission of written comments is November 6, 2008, and for pre-registration to attend the meeting, including registering to present oral comments, is November 13, 2008. Persons needing interpreting services in order to attend should contact 301-402-8180 (voice) or 301-435-1908 (TTY). For other accommodations while on the NIEHS campus, contact 919-541-2475 or e-mail [e-mail]. Requests should be made at least 7 days in advance of the event.

ADDRESSES:

The NTP BSC meeting will be held in the Rodbell Auditorium, Rall Building at the NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709. Public comments on all agenda topics and any other correspondence should be submitted to Dr. Barbara Shane, Executive Secretary for the NTP BSC, NTP Office of Liaison, Policy and Review, NIEHS, P.O. Box 12233, MD A3-01, Research Triangle Park, NC 27709; telephone: [phone]; fax: [phone]; or e-mail: [e-mail]. Courier address: NIEHS, 111 T.W. Alexander Drive, Room A322, Research Triangle Park, NC 27709.

FOR FURTHER INFORMATION CONTACT:

Dr. Barbara Shane (telephone: [phone] or e-mail: [e-mail]).

SUPPLEMENTARY INFORMATION:

Preliminary Agenda Topics and Availability of Meeting Materials

November 20-21, 2008

• Update of NTP activities
• NTP testing program: nominations and proposed research projects on bisphenol AF, dimethylamine borane, ethylene glycol 2-ethylhexyl ether, hydroxyurea, L-beta-methylaminoalanine, and triclosan
• BSC working group report on criteria for evaluating outcomes in immunotoxicology studies
• BSC working group report on criteria for evaluating outcomes in reproductive toxicology studies
• BSC working group report on criteria for evaluating outcomes in developmental toxicology studies
• Toxicology of DNA-based therapies
• Concept review: production of mold materials
• Sources of variability in NTP toxicogenomic studies
• Update on the High Throughput Screening Initiative

The preliminary agenda, roster of NTP BSC members and ad hoc reviewers, draft NTP research concepts, public comments, and any additional information, when available, will be posted on the NTP BSC meeting Web site (http://ntp.niehs.nih.gov/​go/​165) or may be requested in hardcopy from the Executive Secretary for the NTP BSC (see ADDRESSES above). Updates to the agenda will also be posted to this site. Following the meeting, summary minutes will be prepared and made available on the NTP meeting Web site.

NTP Testing Program: Nominations and Proposed Research Projects

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. 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 evaluating dose-response relationships. Nominations are subject to a multi-step, formal process of review before selections for testing are made and toxicological studies are designed and implemented. 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 BSC, the NTP Executive Committee—the NTP federal interagency policy body, and the public. 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”).

Table 1 lists new nominations to be reviewed at the NTP BSC meeting. Background documents for each nomination are available on the NTP Web site at http://ntp.niehs.nih.gov/​go/​nom. The NTP invites interested parties to submit written comments, provide supplementary information, or present oral comments at the NTP BSC meeting on the nominated substances and preliminary study recommendations (see “Request for Comments” below). The NTP welcomes toxicology 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 high-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. Although the deadline for submission of written comments to be considered at the NTP BSC meeting is November 6, 2008 (see “Request for Comments” below), the NTP welcomes comments or additional information on these study nominations at any time.

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

Substance [CAS No.]	Nominated by 1	Nomination rationale	Preliminary study recommendations 2
Bisphenol AF [1478-61-1]	NIEHS	Moderate production and use in polymer synthesis; short-term studies suggest potential for endocrine disruption and adverse reproductive effects; lack of adequate toxicity data	—Comprehensive toxicological characterization.
Dimethylamine borane [74-94-2]	National Institute for Occupational Safety and Health	Possible contact sensitizer and systemic toxicant but insufficient evidence as determined by the NIOSH Dermal Subject Matter Expert Workgroup	—Dermal absorption studies. —Skin sensitization studies. —Subchronic dermal toxicity studies with neurotoxicity and behavioral assessments.
Ethylene glycol 2-ethylhexyl ether [1559-35-9]	NIEHS	High production volume; potential worker exposures; suspicion of toxicity based on chemical structure; lack of adequate toxicity data	—Reproductive and developmental toxicity studies.
Hydroxyurea [127-07-1]	NIEHS and Private Individual	Long-term safety concern when used as therapy for sickle cell anemia; NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) Expert Panel identified a critical data need for multi-generational experimental animal studies to assess the long-term effects of prenatal and postnatal exposures on postnatal development including developmental neurotoxicity, reproductive function, and carcinogenicity	No experimental animal toxicity studies at this time; human studies currently being considered by the NIH and other federal agencies may address outstanding safety concerns.
L-beta-Methylaminoalanine [15920-93-1]	NIEHS	Natural product produced by cyanobacteria with localized and potentially widespread environmental occurrence; suspected risk factor for neurological disease(s); lack of adequate toxicity data	—Absorption, distribution, metabolism, and elimination studies. —Neurotoxicity studies. —Biomolecular screening studies.
Triclosan [3380-34-5]	Private Individual and U.S. Food and Drug Administration	Widespread use in consumer products; frequent and long-term exposure for all age groups; lack of adequate toxicity data for dermal exposures	—Carcinogenicity studies via dermal administration. —Phototoxicity studies. —Reproductive toxicity studies.
1 National Institute of Environmental Health Sciences (NIEHS).
2 The term “comprehensive toxicological characterization” in this table refers to the approximate scope of a research program to address toxicological data needs. The types of toxicological studies that would be considered by NTP staff during the conceptualization and design of a research program are biomolecular screening, in vitro mechanistic, in vitro and in vivo genotoxicity, absorption, disposition, metabolism, and elimination, short-term repeat dose (2-4 weeks) in vivo studies, subchronic toxicity (13-26 weeks), chronic toxicity (1-2 years), carcinogenicity in conventional or genetically modified rodent models, organ systems toxicity (immunotoxicity, reproductive and developmental toxicity, neurotoxicity), in vivo mechanistic, toxicokinetics, and other special studies as appropriate (e.g., chemistry, toxicogenomics, phototoxicity).

To facilitate review of proposed research projects by the NTP BSC and the public, NTP staff developed a draft research concept document for each nomination recommended for study. A research concept is a brief document outlining the nomination or study rationale, and the significance, study approach, and expected outcome of a proposed research program tailored for each nomination. The purpose of these research concepts is to outline the general elements of a program of study that would address the specific issues that prompted the nomination, but also encompass studies that may address larger public health issues or topics in toxicology that could be addressed appropriately through studies on the nominated substance(s). Draft research concepts for the new nominations listed in Table 1 will be available on the NTP BSC meeting page (http://ntp.niehs.nih.gov/​go/​165) by October 9, 2008.

Attendance and Registration

The meeting is scheduled for November 20-21, 2008, beginning at 8:30 a.m. on each day and continuing to 5 p.m. on November 20 and on November 21 until adjournment. The meeting is open to the public with attendance limited only by the space available. Individuals who plan to attend are encouraged to register online at the NTP BSC meeting Web site (http://ntp.niehs.nih.gov/​go/​165) by November 13, 2008, to facilitate planning for the meeting. The NTP is making plans to videocast the meeting through the Internet at http://www.niehs.nih.gov/​news/​video/​live.

Request for Comments

Written comments submitted in response to this notice should be received by November 6, 2008. Comments will be posted on the NTP BSC meeting Web site and persons submitting them will be identified by their name and affiliation and/or sponsoring organization, if applicable. Persons submitting written comments should include their name, affiliation (if applicable), phone, e-mail, and sponsoring organization (if any) with the document.

Time will be allotted during the meeting for the public to present oral comments to the NTP BSC on the agenda topics. Each organization is allowed one time slot per agenda topic. At least 7 minutes will be allotted to each speaker, and if time permits, may be extended to 10 minutes at the discretion of the NTP BSC chair. Persons wishing to present oral comments are encouraged to pre-register on the NTP meeting Web site. Registration for oral comments will also be available on-site, although time allowed for presentation by on-site registrants may be less than that for pre-registered speakers and will be determined by the number of persons who register at the meeting.

Persons registering to make oral comments are asked, if possible, to send a copy of their statement to the Executive Secretary for the NTP BSC (see ADDRESSES above) by November 13, 2008, to enable review by the NTP BSC prior to the meeting. Written statements can supplement and may expand the oral presentation. If registering on-site and reading from written text, please bring 40 copies of the statement for distribution to the NTP BSC and NIEHS/NTP staff and to supplement the record.

Background Information on the NTP Board of Scientific Counselors

The NTP BSC is a technical advisory body comprised of scientists from the public and private sectors that provides primary scientific oversight to the overall program and its centers. Specifically, the NTP BSC advises the NTP on matters of scientific program content, both present and future, and conducts periodic review of the program for the purpose of determining and advising on the scientific merit of its activities and their overall scientific quality. Its members are selected from recognized authorities knowledgeable in fields such as toxicology, pharmacology, pathology, biochemistry, epidemiology, risk assessment, carcinogenesis, mutagenesis, molecular biology, behavioral toxicology, neurotoxicology, immunotoxicology, reproductive toxicology or teratology, and biostatistics. Members serve overlapping terms of up to four years. NTP BSC meetings are held annually or biannually.

Dated: September 23, 2008.

Samuel H. Wilson,

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