National Toxicology Program (NTP), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Announcement of an Independent Scientific Peer Review Meeting on the Use of In Vitro Testing Methods for Estimating Starting Doses for Acute Oral Systemic Toxicity Tests and Request for Comments, 14229-14231 [E6-4075]

Download as PDF Federal Register / Vol. 71, No. 54 / Tuesday, March 21, 2006 / Notices provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications and the discussions could disclose confidential trade secrets or commercial property such as patentable material, and personal information concerning individuals associated with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Environmental Health Sciences Special Emphasis Panel Review of Conferences (R13s) and Cooperative Agreement (U13). Date: April 12, 2006. Time: 1 p.m. to 5 p.m. Agenda: To review and evaluate grant applications. Place: NIEHS/National Institutes of Health, Building 4401, East Campus, 79 T.W. Alexander Drive, Research Triangle Park, NC 27709, (Telephone Conference Call). Contact Person: Linda K Bass, PhD, Scientific Review Administrator, Scientific Review Branch, Office of Program Operations, Division of Extramural Research and Training, Nat. Institute of Environmental Health Sciences, P.O. Box 12233, MD EC–30, Research Triangle Park, NC 27709, 919/541– 1307. (Catalogue of Federal Domestic Assistance Program Nos. 93.115, Biometry and Risk Estimation—Health Risks from Environmental Exposures; 93.142, NIEHS Hazardous Waste Worker Health and Safety Training; 93.143, NIEHS Superfund Hazardous Substances—Basic Research and Education; 93.894, Resources and Manpower Development in the Environmental Health Sciences; 93.113, Biological Response to Environmental Health Hazards; 93.114, Applied Toxicological Research and Testing, National Institutes of Health, HHS) Dated: March 13, 2006. Anna Snouffer, Acting Director, Office of Federal Advisory Committee Policy. [FR Doc. 06–2738 Filed 3–20–06; 8:45 am] National Institutes of Health National Library of Medicine; Notice of Closed Meeting sroberts on PROD1PC70 with NOTICES Dated: March 15, 2006. Anna Snouffer, Acting Director, Office of Federal Advisory Committee Policy. [FR Doc. 06–2720 Filed 3–20–06; 8:45 am] BILLING CODE 4140–01–M DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP), NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Announcement of an Independent Scientific Peer Review Meeting on the Use of In Vitro Testing Methods for Estimating Starting Doses for Acute Oral Systemic Toxicity Tests and Request for Comments National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). ACTION: Meeting Announcement and Request for Comment. DEPARTMENT OF HEALTH AND HUMAN SERVICES Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2), notice is hereby given of the following meeting. The meeting will be closed to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications and the discussions could disclose confidential trade secrets or commercial 19:01 Mar 20, 2006 Name of Committee: National Library of Medicine Special Emphasis Panel, Loan Repayment Program—IAR. Date: April 27, 2006. Time: 1 p.m. to 4 p.m. Agenda: To review and evaluate grant applications. Place: National Library of Medicine, 6705 Rockledge Drive, Suite 301, Bethesda, MD 20817, (Telephone Conference Call). Contact Person: Zoe E. Huang, MD, Health Science Administrator, Extramural Programs, National Library of Medicine, Rockledge 1 Building, 6705 Rockledge Drive, Suite 301, MSC 7968, Bethesda, MD 20892–7968. 301– 594–4937. huangz@mail.nih.gov. (Catalogue of Federal Domestic Assistance Program Nos. 93.879, Medicine Library Assistance, National Institutes of Health, HHS) AGENCY: BILLING CODE 4140–01–M VerDate Aug<31>2005 property such as patentable material, and personal information concerning individuals associated with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of personal privacy. Jkt 208001 SUMMARY: NICEATM in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) announces a public, independent, scientific peer review meeting to evaluate the validation status of the in vitro 3T3 and normal human keratinocyte (NHK) neutral red uptake (NRU) basal cytotoxicity test methods for estimating starting doses for in vivo acute oral toxicity tests. These two in vitro cytotoxicity test methods are proposed as adjuncts to the in vivo acute oral toxicity tests to refine (i.e., to lessen PO 00000 Frm 00066 Fmt 4703 Sfmt 4703 14229 or avoid pain and distress) and/or reduce animal use. At this meeting, a scientific peer review panel (‘‘Panel’’) will peer review the background review document (BRD) on the 3T3 and NHK cytotoxicity test methods, evaluate the extent that the BRD addresses established validation and acceptance criteria, and provide comment on the draft ICCVAM recommendations on the proposed use of these test methods, draft test method protocols, and draft performance standards. NICEATM requests public comments on the BRD, draft ICCVAM test method recommendations, draft test method protocols, and draft performance standards. The meeting will be held on May 23, 2006, from 8:30 a.m. to 5 p.m. The meeting is open to the public with attendance limited only by the space available. In order to facilitate planning for this meeting, persons wishing to attend the meeting are asked to register via the ICCVAM/NICEATM Web site (https://iccvam.niehs.nih.gov) by May 12, 2006. ADDRESSES: The meeting will be held at the National Institutes of Health (NIH), Natcher Conference Center, 45 Center Drive, Bethesda, MD 20892. FOR FURTHER INFORMATION CONTACT: Correspondence should be sent by mail, fax, or email to Dr. William S. Stokes, NICEATM Director, NIEHS, P.O. Box 12233, MD EC–17, Research Triangle Park, NC 27709, (phone) 919–541–2384, (fax) 919–541–0947, (e-mail) niceatm@niehs.nih.gov, Courier address: NICEATM, 79 T.W. Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 27709. SUPPLEMENTARY INFORMATION: DATES: Background In September 2001, ICCVAM recommended that in vitro basal cytotoxicity test methods be considered as tools for estimating starting doses for in vivo acute systemic toxicity studies (Federal Register Vol. 66, No. 189, pp. 49686–7, September 28, 2001). The recommendations were based on the Report of the International Workshop on In Vitro Methods for Assessing Acute Systemic Toxicity (ICCVAM, 2001a). The Guidance Document on Using In Vitro Data to Estimate In Vivo Starting Doses for Acute Toxicity (ICCVAM, 2001b) was also made available at that time. The guidance document provided standard procedures for two in vitro basal cytotoxicity test methods and instructions for using these test methods to estimate starting doses for in vivo testing. E:\FR\FM\21MRN1.SGM 21MRN1 sroberts on PROD1PC70 with NOTICES 14230 Federal Register / Vol. 71, No. 54 / Tuesday, March 21, 2006 / Notices U.S. Federal agencies’ responses to the ICCVAM recommendations from the International Workshop were announced in 2004 (Federal Register Vol. 69, No. 47, pp. 11448–9, March 10, 2004). The U.S. Federal agencies agreed to encourage, to the extent applicable, the use of in vitro tests for determining starting doses for acute oral systemic toxicity testing. Furthermore, the U.S. Environmental Protection Agency (EPA) specifically encouraged those participating in the High Production Volume Challenge Program to consider using the recommended in vitro test methods as a supplemental component when conducting any new in vivo acute oral toxicity studies for the program (https://www.epa.gov/chemrtk/ toxprtow.htm). In 2002, NICEATM and the European Committee on the Validation of Alternative Methods began a collaborative validation study to independently evaluate the usefulness of two in vitro basal cytotoxicity test methods proposed for estimating starting doses for in vivo rodent acute oral toxicity tests. In vitro NRU cytotoxicity test methods using either BALB/c 3T3 fibroblasts, a mouse cell line, or NHK cells, primary human epidermal cells, were evaluated in a multi-laboratory international validation study. During the pre-validation phases of the study, the test method protocols were standardized further and revised to improve their intra- and inter-laboratory reproducibilities. NICEATM recommended using the revised test method protocols (Federal Register, Vol. 69, No. 201, pp. 61504–5, October 19, 2004) rather than the standard procedures outlined in the guidance document (ICCVAM, 2001b). During the validation study, 72 reference chemicals were tested using the 3T3 and NHK NRU test methods. The in vitro NRU cytotoxicity test results were used to estimate acute oral LD50 values, which in turn were used to identify the starting doses for simulated acute oral toxicity testing using the Up-and-Down Procedure (UDP; EPA 2002; OECD 2001a) and the Acute Toxic Class method (ATC; OECD 2001b). The in vivo test simulations were used to compare the number of animals used and the number of deaths expected to occur when starting with the default starting doses versus using a starting dose based on in vitro cytotoxicity data. To assist in an evaluation of the usefulness of these two in vitro NRU basal cytotoxicity test methods for estimating starting doses for in vivo. acute oral toxicity tests, NICEATM requested the submission of existing in vivo and in vitro acute toxicity data VerDate Aug<31>2005 19:30 Mar 20, 2006 Jkt 208001 (Federal Register, Vol. 69, No. 201, pp. 61504–5, October 19, 2004 and Vol. 65, No. 115, pp. 37400–3, June 14, 2000). In 2005, NICEATM announced a request for nominations of scientists to serve on the Panel and again requested existing in vivo and in vitro data (Federal Register Vol. 70, No. 54, pp. 14473–4, March 22, 2005). Expert Panel Meeting The purpose of this meeting is the scientific peer review evaluation of the validation status of the 3T3 and NHK NRU basal cytotoxicity test methods to determine starting doses for the UDP and ATC acute oral toxicity test methods in order to refine and reduce the use of animals. The Panel will first peer review the BRD on the 3T3 and NHK cytotoxicity test methods and then evaluate the extent that the BRDs address established validation and acceptance criteria (Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods, NIH Publication No. 97–3981, https:// iccvam.niehs.nih.gov). The Panel will also be asked to provide comment on the draft ICCVAM test method recommendations, draft standardized test method protocols, and draft performance standards. Information about the Panel meeting, including a roster of the members of the Panel and the agenda, will be made available two weeks prior to the meeting on the ICCVAM/NICETATM Web site (https:// iccvam.niehs.nih.gov) or can be obtained after that date by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT above). Attendance and Registration The public Panel meeting will take place May 23, 2006, at the NIH Campus, Natcher Conference Center, Bethesda, MD (a map of the NIH Campus and other visitor information are available at https://www.nih.gov/about/visitor/ index.htm). The meeting will begin at 8:30 a.m. and conclude at approximately 5 p.m. Persons needing special assistance, such as sign language interpretation or other reasonable accommodation in order to attend, should contact 919–541–2475 voice, 919–541–4644 TTY (text telephone), through the Federal TTY Relay System at 800–877–8339, or by e-mail to niehsoeeo@niehs.nih.gov. Requests should be made at least seven business days in advance of the event. PO 00000 Frm 00067 Fmt 4703 Sfmt 4703 Availability of the BRD and Draft ICCVAM Recommendations NICEATM prepared a BRD on the 3T3 and NHK NRU basal cytotoxicity test methods that contains comprehensive summaries of the data generated in the validation study, an analysis of the accuracy and reliability of the two test methods, a simulation analysis of the refinement and reduction in animal use that would occur if these tests were used as adjuncts to the UDP and ATC acute oral systemic toxicity test methods, and related information characterizing the validation status of these assays. The BRD, draft ICCVAM test method recommendations, draft test method protocols, and draft test method performance standards will be provided to the Panel and made available to the public. Copies of these materials can be obtained from the ICCVAM/NICEATM Web site (https://iccvam.niehs.nih.gov) or by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT above). Request for Comments NICEATM invites the submission of written comments on the BRD, draft ICCVAM test method recommendations, draft test method protocols, and draft test method performance standards. When submitting written comments, it is important to refer to this Federal Register notice and include appropriate contact information (name, affiliation, mailing address, phone, fax, email and sponsoring organization, if applicable). Written comments should be sent by mail, fax, or email to Dr. William Stokes, Director of NICEATM, at the address listed above not later than May 5, 2006. All comments received will be placed on the ICCVAM/NICEATM website and made available to the Panel, ICCVAM agency representatives, and attendees at the meeting. This meeting is open to the public and time will be provided for the presentation of public oral comments at designated times during the peer review. Members of the public who wish to present oral statements at the meeting (one speaker per organization) should contact NICEATM (see FOR FURTHER INFORMATION CONTACT above) no later than May 12, 2006. Speakers will be assigned on a consecutive basis and up to seven minutes will be allotted per speaker. Persons registering to make comments are asked to provide a written copy of their statement by May 12, 2006, so that copies can be distributed to the Panel prior to the meeting or if this is not possible to bring 40 copies to the meeting. Written statements can supplement and expand the oral presentation. Each speaker is asked to E:\FR\FM\21MRN1.SGM 21MRN1 Federal Register / Vol. 71, No. 54 / Tuesday, March 21, 2006 / Notices provide contact information (name, affiliation, mailing address, phone, fax, email and sponsoring organization, if applicable) when registering to make oral comments. Summary minutes and a final report of the Panel will be available following the meeting at the ICCVAM/NICEATM Web site (https://iccvam.niehs.nih.gov). ICCVAM will consider the conclusions and recommendations from the Panel and any public comments received in finalizing test method recommendations and performance standards for these test methods. sroberts on PROD1PC70 with NOTICES Background Information on ICCVAM and NICEATM ICCVAM is an interagency committee composed of representatives from 15 U.S. Federal regulatory and research agencies that use or generate toxicological information. ICCVAM conducts technical evaluations of new, revised, and alternative methods with regulatory applicability and promotes the scientific validation and regulatory acceptance of toxicological test methods that more accurately assess the safety and hazards of chemicals and products while refining (less pain and distress), reducing, and replacing animal use. The ICCVAM Authorization Act of 2000 (Pub. L. 106–545, available at https:// iccvam.niehs.nih.gov/about/ PL106545.htm) establishes ICCVAM as a permanent interagency committee of the NIEHS under the NICEATM. NICEATM administers the ICCVAM and provides scientific and operational support for ICCVAM-related activities. NICEATM and ICCVAM work collaboratively to evaluate new and improved test methods applicable to the needs of U.S. Federal agencies. Additional information about ICCVAM and NICEATM can be found at the ICCVAM/ NICEATM Web site: https:// iccvam.niehs.nih.gov. References EPA. 2002a. Health Effects Test Guidelines OPPTS 870.1100 Acute Oral Toxicity. EPA 712–C–02–190. Washington, DC: U.S. Environmental Protection Agency. ICCVAM. 2001a. Report of the international workshop on in vitro methods for assessing acute systemic toxicity. NIH Publication 01–4499. Research Triangle Park, NC: National Institute for Environmental Health Sciences. Available at: https:// iccvam.niehs.nih.gov/. ICCVAM. 2001b. Guidance document on using in vitro data to estimate in vivo starting doses for acute toxicity. NIH Publication 01–4500. Research Triangle Park, NC: National Institute for Environmental Health Sciences. Available at: https:// iccvam.niehs.nih.gov/. OECD. 2001a. VerDate Aug<31>2005 19:30 Mar 20, 2006 Jkt 208001 Guideline for Testing of Chemicals, 425, Acute Oral Toxicity—Up-and-Down Procedure. Paris France: OECD. Available at: https://www.oecd.org [accessed June 2, 2004]. OECD. 2001b. Guideline For Testing of Chemicals, 423, Acute Oral Toxicity—Acute Toxic Class Method. Paris France: OECD. Dated: March 9, 2006. Samuel H. Wilson, Deputy Director, National Institute of Environmental Health Sciences and National Toxicology Program. [FR Doc. E6–4075 Filed 3–20–06; 8:45 am] BILLING CODE 4140–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Center for Scientific Review; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2), notice is hereby given of the following meetings. The meetings will be closed to the public in accordance with the provisions set forth in sections 552b(c)(4) and 552b(c)(6), Title 5 U.S.C., as amended. The grant applications and the discussions could disclose confidential trade secrets or commercial property such as patentable material, and personal information concerning individuals associated with the grant applications, the disclosure of which would constitute a clearly unwarranted invasion of personal privacy. Name of Committee: Center for Scientific Review Special Emphasis Panel, Skeletal Biology. Date: March 27, 2006. Time: 1 p.m. to 2:30 p.m. Agenda: To review and evaluate grant applications. Place: National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD 20892, (Telephone Conference Call). Contact Person: Priscilla B. Chen, PhD, Scientific Review Administrator, Center for Scientific Review, National Institutes of Health, 6701 Rockledge Drive, Room 4104, MSC 7814, Bethesda, MD 20892. (301) 594– 1787. chenp@csr.nih.gov. This notice is being published less than 15 days prior to the meeting due to the timing limitations imposed by the review and funding cycle. Name of Committee: Center for Scientific Review Special Emphasis Panel, Computational Modeling and Development. Date: April 5, 2006. Time: 2 p.m. to 4 p.m. Agenda: To review and evaluate grant applications. Place: National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD 20892, (Telephone Conference Call). PO 00000 Frm 00068 Fmt 4703 Sfmt 4703 14231 Contact Person: Sherry L. Dupere, PhD, Scientific Review Administrator, Center for Scientific Review, National Institutes of Health, 6701 Rockledge Drive, Room 5136, MSC 7843, Bethesda, MD 20892. (301) 435– 1021. duperes@csr.nih.gov. Name of Committee: Center for Scientific Review Special Emphasis Panel, Musculoskeletal Rehabilitation Sciences. Date: April 7, 2006. Time: 1 p.m. to 3:30 p.m. Agenda: To review and evaluate grant applications. Place: National Institutes of Health, 6701 Rockledge Drive, Bethesda, MD 20892, (Telephone Conference Call). Contact Person: John P. Holden, PhD, Scientific Review Administrator, Center for Scientific Review, National Institutes of Health, 6701 Rockledge Drive, Room 4016J, MSC 7814, Bethesda, MD 20892. (301) 596– 8551. holdenjo@csr.nih.gov. (Catalogue of Federal Domestic Assistance Program Nos. 93.306, Comparative Medicine; 93.333, Clinical Research, 93.306, 93.333, 93.337, 93.393–93.396, 93.837–93.844, 93.846–93.878, 93.892, 93.893, National Institutes of Health, HHS) Dated: March 13, 2006. Anna Snouffer, Acting Director, Office of Federal Advisory Committee Policy. [FR Doc. 06–2739 Filed 3–20–06; 8:45 am] BILLING CODE 4140–01–M DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: The Use of HMG-CoA Inhibitors for the Treatment of Adenocarcinomas and Ewing’s Sarcoma National Institutes of Health, Public Health Service, HHS. ACTION: Notice. AGENCY: SUMMARY: This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR Part 404.7(a)(1)(i), that the National Institutes of Health (NIH), Department of Health and Human Services (HHS), is contemplating the grant of an exclusive patent license to practice the inventions embodied in U.S. Patent No. 6,040,334 issued March 21, 2000, entitled ‘‘Use of Inhibitors of 3-Hydroxy-3Methylglutaryl Coenzyme A reductase as a Modality in Cancer Therapy’’ [HHS Reference E–146–1992/0–US–23] and related foreign applications to Nascent Oncology, Inc., which has offices in Chapel Hill, North Carolina. The patent rights in these inventions have been assigned and/or exclusively licensed to the Government of the United States of America. E:\FR\FM\21MRN1.SGM 21MRN1

Agencies

[Federal Register Volume 71, Number 54 (Tuesday, March 21, 2006)]
[Notices]
[Pages 14229-14231]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E6-4075]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP), NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Announcement 
of an Independent Scientific Peer Review Meeting on the Use of In Vitro 
Testing Methods for Estimating Starting Doses for Acute Oral Systemic 
Toxicity Tests and Request for Comments

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

ACTION: Meeting Announcement and Request for Comment.

-----------------------------------------------------------------------

SUMMARY: NICEATM in collaboration with the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM) announces a 
public, independent, scientific peer review meeting to evaluate the 
validation status of the in vitro 3T3 and normal human keratinocyte 
(NHK) neutral red uptake (NRU) basal cytotoxicity test methods for 
estimating starting doses for in vivo acute oral toxicity tests. These 
two in vitro cytotoxicity test methods are proposed as adjuncts to the 
in vivo acute oral toxicity tests to refine (i.e., to lessen or avoid 
pain and distress) and/or reduce animal use. At this meeting, a 
scientific peer review panel (``Panel'') will peer review the 
background review document (BRD) on the 3T3 and NHK cytotoxicity test 
methods, evaluate the extent that the BRD addresses established 
validation and acceptance criteria, and provide comment on the draft 
ICCVAM recommendations on the proposed use of these test methods, draft 
test method protocols, and draft performance standards. NICEATM 
requests public comments on the BRD, draft ICCVAM test method 
recommendations, draft test method protocols, and draft performance 
standards.

DATES: The meeting will be held on May 23, 2006, from 8:30 a.m. to 5 
p.m. The meeting is open to the public with attendance limited only by 
the space available. In order to facilitate planning for this meeting, 
persons wishing to attend the meeting are asked to register via the 
ICCVAM/NICEATM Web site (https://iccvam.niehs.nih.gov) by May 12, 2006.

ADDRESSES: The meeting will be held at the National Institutes of 
Health (NIH), Natcher Conference Center, 45 Center Drive, Bethesda, MD 
20892.

FOR FURTHER INFORMATION CONTACT: Correspondence should be sent by mail, 
fax, or email to Dr. William S. Stokes, NICEATM Director, NIEHS, P.O. 
Box 12233, MD EC-17, Research Triangle Park, NC 27709, (phone) 919-541-
2384, (fax) 919-541-0947, (e-mail) niceatm@niehs.nih.gov, Courier 
address: NICEATM, 79 T.W. Alexander Drive, Building 4401, Room 3128, 
Research Triangle Park, NC 27709.

SUPPLEMENTARY INFORMATION:

Background

    In September 2001, ICCVAM recommended that in vitro basal 
cytotoxicity test methods be considered as tools for estimating 
starting doses for in vivo acute systemic toxicity studies (Federal 
Register Vol. 66, No. 189, pp. 49686-7, September 28, 2001). The 
recommendations were based on the Report of the International Workshop 
on In Vitro Methods for Assessing Acute Systemic Toxicity (ICCVAM, 
2001a). The Guidance Document on Using In Vitro Data to Estimate In 
Vivo Starting Doses for Acute Toxicity (ICCVAM, 2001b) was also made 
available at that time. The guidance document provided standard 
procedures for two in vitro basal cytotoxicity test methods and 
instructions for using these test methods to estimate starting doses 
for in vivo testing.

[[Page 14230]]

    U.S. Federal agencies' responses to the ICCVAM recommendations from 
the International Workshop were announced in 2004 (Federal Register 
Vol. 69, No. 47, pp. 11448-9, March 10, 2004). The U.S. Federal 
agencies agreed to encourage, to the extent applicable, the use of in 
vitro tests for determining starting doses for acute oral systemic 
toxicity testing. Furthermore, the U.S. Environmental Protection Agency 
(EPA) specifically encouraged those participating in the High 
Production Volume Challenge Program to consider using the recommended 
in vitro test methods as a supplemental component when conducting any 
new in vivo acute oral toxicity studies for the program (https://
www.epa.gov/chemrtk/toxprtow.htm).
    In 2002, NICEATM and the European Committee on the Validation of 
Alternative Methods began a collaborative validation study to 
independently evaluate the usefulness of two in vitro basal 
cytotoxicity test methods proposed for estimating starting doses for in 
vivo rodent acute oral toxicity tests. In vitro NRU cytotoxicity test 
methods using either BALB/c 3T3 fibroblasts, a mouse cell line, or NHK 
cells, primary human epidermal cells, were evaluated in a multi-
laboratory international validation study. During the pre-validation 
phases of the study, the test method protocols were standardized 
further and revised to improve their intra- and inter-laboratory 
reproducibilities. NICEATM recommended using the revised test method 
protocols (Federal Register, Vol. 69, No. 201, pp. 61504-5, October 19, 
2004) rather than the standard procedures outlined in the guidance 
document (ICCVAM, 2001b). During the validation study, 72 reference 
chemicals were tested using the 3T3 and NHK NRU test methods. The in 
vitro NRU cytotoxicity test results were used to estimate acute oral 
LD50 values, which in turn were used to identify the 
starting doses for simulated acute oral toxicity testing using the Up-
and-Down Procedure (UDP; EPA 2002; OECD 2001a) and the Acute Toxic 
Class method (ATC; OECD 2001b). The in vivo test simulations were used 
to compare the number of animals used and the number of deaths expected 
to occur when starting with the default starting doses versus using a 
starting dose based on in vitro cytotoxicity data.
    To assist in an evaluation of the usefulness of these two in vitro 
NRU basal cytotoxicity test methods for estimating starting doses for 
in vivo. acute oral toxicity tests, NICEATM requested the submission of 
existing in vivo and in vitro acute toxicity data (Federal Register, 
Vol. 69, No. 201, pp. 61504-5, October 19, 2004 and Vol. 65, No. 115, 
pp. 37400-3, June 14, 2000). In 2005, NICEATM announced a request for 
nominations of scientists to serve on the Panel and again requested 
existing in vivo and in vitro data (Federal Register Vol. 70, No. 54, 
pp. 14473-4, March 22, 2005).

Expert Panel Meeting

    The purpose of this meeting is the scientific peer review 
evaluation of the validation status of the 3T3 and NHK NRU basal 
cytotoxicity test methods to determine starting doses for the UDP and 
ATC acute oral toxicity test methods in order to refine and reduce the 
use of animals. The Panel will first peer review the BRD on the 3T3 and 
NHK cytotoxicity test methods and then evaluate the extent that the 
BRDs address established validation and acceptance criteria (Validation 
and Regulatory Acceptance of Toxicological Test Methods: A Report of 
the ad hoc Interagency Coordinating Committee on the Validation of 
Alternative Methods, NIH Publication No. 97-3981, https://
iccvam.niehs.nih.gov). The Panel will also be asked to provide comment 
on the draft ICCVAM test method recommendations, draft standardized 
test method protocols, and draft performance standards. Information 
about the Panel meeting, including a roster of the members of the Panel 
and the agenda, will be made available two weeks prior to the meeting 
on the ICCVAM/NICETATM Web site (https://iccvam.niehs.nih.gov) or can be 
obtained after that date by contacting NICEATM (see FOR FURTHER 
INFORMATION CONTACT above).

Attendance and Registration

    The public Panel meeting will take place May 23, 2006, at the NIH 
Campus, Natcher Conference Center, Bethesda, MD (a map of the NIH 
Campus and other visitor information are available at https://
www.nih.gov/about/visitor/index.htm). The meeting will begin at 8:30 
a.m. and conclude at approximately 5 p.m. Persons needing special 
assistance, such as sign language interpretation or other reasonable 
accommodation in order to attend, should contact 919-541-2475 voice, 
919-541-4644 TTY (text telephone), through the Federal TTY Relay System 
at 800-877-8339, or by e-mail to niehsoeeo@niehs.nih.gov. Requests 
should be made at least seven business days in advance of the event.

Availability of the BRD and Draft ICCVAM Recommendations

    NICEATM prepared a BRD on the 3T3 and NHK NRU basal cytotoxicity 
test methods that contains comprehensive summaries of the data 
generated in the validation study, an analysis of the accuracy and 
reliability of the two test methods, a simulation analysis of the 
refinement and reduction in animal use that would occur if these tests 
were used as adjuncts to the UDP and ATC acute oral systemic toxicity 
test methods, and related information characterizing the validation 
status of these assays. The BRD, draft ICCVAM test method 
recommendations, draft test method protocols, and draft test method 
performance standards will be provided to the Panel and made available 
to the public. Copies of these materials can be obtained from the 
ICCVAM/NICEATM Web site (https://iccvam.niehs.nih.gov) or by contacting 
NICEATM (see FOR FURTHER INFORMATION CONTACT above).

Request for Comments

    NICEATM invites the submission of written comments on the BRD, 
draft ICCVAM test method recommendations, draft test method protocols, 
and draft test method performance standards. When submitting written 
comments, it is important to refer to this Federal Register notice and 
include appropriate contact information (name, affiliation, mailing 
address, phone, fax, email and sponsoring organization, if applicable). 
Written comments should be sent by mail, fax, or email to Dr. William 
Stokes, Director of NICEATM, at the address listed above not later than 
May 5, 2006. All comments received will be placed on the ICCVAM/NICEATM 
website and made available to the Panel, ICCVAM agency representatives, 
and attendees at the meeting.
    This meeting is open to the public and time will be provided for 
the presentation of public oral comments at designated times during the 
peer review. Members of the public who wish to present oral statements 
at the meeting (one speaker per organization) should contact NICEATM 
(see FOR FURTHER INFORMATION CONTACT above) no later than May 12, 2006. 
Speakers will be assigned on a consecutive basis and up to seven 
minutes will be allotted per speaker. Persons registering to make 
comments are asked to provide a written copy of their statement by May 
12, 2006, so that copies can be distributed to the Panel prior to the 
meeting or if this is not possible to bring 40 copies to the meeting. 
Written statements can supplement and expand the oral presentation. 
Each speaker is asked to

[[Page 14231]]

provide contact information (name, affiliation, mailing address, phone, 
fax, email and sponsoring organization, if applicable) when registering 
to make oral comments.
    Summary minutes and a final report of the Panel will be available 
following the meeting at the ICCVAM/NICEATM Web site (https://
iccvam.niehs.nih.gov). ICCVAM will consider the conclusions and 
recommendations from the Panel and any public comments received in 
finalizing test method recommendations and performance standards for 
these test methods.

Background Information on ICCVAM and NICEATM

    ICCVAM is an interagency committee composed of representatives from 
15 U.S. Federal regulatory and research agencies that use or generate 
toxicological information. ICCVAM conducts technical evaluations of 
new, revised, and alternative methods with regulatory applicability and 
promotes the scientific validation and regulatory acceptance of 
toxicological test methods that more accurately assess the safety and 
hazards of chemicals and products while refining (less pain and 
distress), reducing, and replacing animal use. The ICCVAM Authorization 
Act of 2000 (Pub. L. 106-545, available at https://iccvam.niehs.nih.gov/
about/PL106545.htm) establishes ICCVAM as a permanent interagency 
committee of the NIEHS under the NICEATM. NICEATM administers the 
ICCVAM and provides scientific and operational support for ICCVAM-
related activities. NICEATM and ICCVAM work collaboratively to evaluate 
new and improved test methods applicable to the needs of U.S. Federal 
agencies. Additional information about ICCVAM and NICEATM can be found 
at the ICCVAM/NICEATM Web site: https://iccvam.niehs.nih.gov.

References

EPA. 2002a. Health Effects Test Guidelines OPPTS 870.1100 Acute Oral 
Toxicity. EPA 712-C-02-190. Washington, DC: U.S. Environmental 
Protection Agency.
ICCVAM. 2001a. Report of the international workshop on in vitro 
methods for assessing acute systemic toxicity. NIH Publication 01-
4499. Research Triangle Park, NC: National Institute for 
Environmental Health Sciences. Available at: https://
iccvam.niehs.nih.gov/.
ICCVAM. 2001b. Guidance document on using in vitro data to estimate 
in vivo starting doses for acute toxicity. NIH Publication 01-4500. 
Research Triangle Park, NC: National Institute for Environmental 
Health Sciences. Available at: https://iccvam.niehs.nih.gov/. OECD. 
2001a. Guideline for Testing of Chemicals, 425, Acute Oral 
Toxicity--Up-and-Down Procedure. Paris France: OECD. Available at: 
https://www.oecd.org [accessed June 2, 2004]. OECD. 2001b. Guideline 
For Testing of Chemicals, 423, Acute Oral Toxicity--Acute Toxic 
Class Method. Paris France: OECD.

    Dated: March 9, 2006.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
 [FR Doc. E6-4075 Filed 3-20-06; 8:45 am]
BILLING CODE 4140-01-P

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