E8-7831. 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 composed of scientists from the public and private sectors and 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 June 11-12, 2008. The deadline for submission of written comments is May 23, 2008, and for pre-registering to attend the meeting, including providing notice of intent to present oral comments, is June 4, 2008. Persons needing interpreting services in order to attend should contact 301-402-8180 (voice) or 301-435-1908 (TTY). For other accommodations, 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 at the Radisson Hotel Research Triangle Park, 150 Park 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

June 11-12, 2008

• Update of NTP activities.
• Center for the Evaluation of Risks to Human Reproduction: Peer review of the draft NTP Brief on Bisphenol A.
• Criteria for evaluating outcomes in reproductive, developmental, and immunotoxicology studies.
• Report on the NTP BSC Technical Reports Review Subcommittee meeting held February 27-28, 2008.
• NTP studies of DNA-based therapies.
• NTP testing program: Proposed research projects on dimorpholinodiethyl ether, 2-ethylhexyl-p-methoxycinnamate, furan, melamine and cyanuric acid, 4,7,10-trioxatridecane-1,13-diamine, and tetravalent and pentavalent vanadium compounds.
• Update on the High Throughput Screening Initiative.
• Update on the Host Susceptibility Program.

The preliminary agenda, roster of NTP BSC members and ad hoc reviewers, proposed NTP research projects, 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). Following the meeting, summary minutes will be prepared and made available on the NTP meeting Web site.

Peer Review of the Draft NTP Brief on Bisphenol A

The NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) conducts scientifically based assessments of the potential for chemicals to adversely affect human reproduction and development. CERHR follows a multi-step process for its evaluations (66 FR 37047). Currently, CERHR is conducting an evaluation of bisphenol A (CAS RN: 80-5-07), a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics have many applications including food and drink packaging, compact discs, and medical devices, while epoxy resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. CERHR selected bisphenol A for evaluation because of its (1) High production volume, (2) widespread human exposure, (3) evidence of reproductive toxicity in laboratory animals, and (4) public concern.

As part of its evaluation process, CERHR has prepared the draft NTP Brief on bisphenol A that contains the NTP's conclusions and scientific support on whether or not exposure to this chemical presents a concern for human reproduction or the development of children. The draft brief is based on the CERHR Expert Panel Report on Bisphenol A released November 30, 2007, public comments on that report (the report and comments are available at http://cerhr.niehs.nih.gov/​chemicals/​bisphenol/​pubcomm-bisphenol.html), and new studies related to the toxicity or biological activity of bisphenol A published since the February 2007 cut-off date for literature for the expert panel's deliberations.

The draft brief will undergo peer review at the NTP BSC meeting. The NTP invites written public comments on the draft NTP Brief on Bisphenol A and/or presentation of oral comments at the NTP BSC meeting (see “Request for Comments” below). The draft brief will be available on the CERHR Web site (http://cerhr.niehs.nih.gov/​chemicals/​bisphenol/​bisphenol.html) and the NTP BSC meeting Web site (http://ntp.niehs.nih.gov/​go/​165) on April 15, 2008.

NTP Testing Program: 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, and/or present oral comments at the NTP BSC meeting on the nominated substances and preliminary study recommendations that appear in Table 1 (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 May 23, 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
Dimorpholinodiethyl ether [6425-39-4]	NCI	High production volume; potential worker exposures; lack of adequate toxicological data; suspicion of toxicity based on structure	—Initial toxicological characterization. —Studies to assess the potential for nitrosation.
2-Ethylhexyl p-methoxycinnamate [5466-77-3]	NCI	High production volume; widespread consumer exposure as a common sunscreen active ingredient; reported estrogenic and reproductive effects	—Comprehensive toxicological characterization including carcinogenicity and developmental toxicity studies. —Characterization of photodecomposition products.
4,7,10-Trioxatridecane-1,13-diamine [4246-51-9]	NCI	High production volume; potential worker exposures; lack of adequate toxicological data; acutely toxic	—Biomolecular screening studies. —Genotoxicity studies.
Vanadium, tetravalent and pentavalent forms	NIEHS, U.S. Environmental Protection Agency	Widespread occurrence as drinking water contaminant and use as a dietary supplement; EPA Drinking Water Contaminant Candidate List research need; pentavalent form is carcinogenic via the inhalation route; inadequate data to assess risk of oral exposures	—Comprehensive toxicological characterization. —Chronic toxicity and carcinogenicity studies via oral route of administration. —Multi-generation reproductive and developmental toxicity studies.
1 National Institute of Environmental Health Sciences (NIEHS); National Cancer Institute (NCI).
2 The terms “initial toxicological characterization” and “comprehensive toxicological characterization” in this table refer 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 for each are:
—Initial toxicological characterization: Biomolecular screening, in vitro mechanistic, in vitro and in vivo genotoxicity, absorption, disposition, metabolism, and elimination, and short-term repeat dose (2-4 weeks) in vivo studies.
—Comprehensive toxicological characterization: All of the aforementioned plus 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 appropriately addressed through studies on the nominated agent. 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 May 7, 2008.

In addition to review of the new nominations in Table 1, the NTP BSC will review proposed research projects for (1) furan [CAS RN: 110-00-9]; and (2) melamine [CAS RN: 108-78-1] and cyanuric acid [CAS RN: 108-80-5]. Draft research concepts for these proposed projects will be available on the NTP BSC meeting page (http://ntp.niehs.nih.gov/​go/​165) by May 7, 2008.

Attendance and Registration

The meeting is scheduled for June 11-12, 2008, beginning at 8:30 a.m. on each day and continuing to 5 p.m. on June 1 and on June 12 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 June 4, 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 May 23, 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. 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 June 4, 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: April 4, 2008.

Samuel H. Wilson,

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