National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH).
Meeting announcement and request for comments.
NICEATM in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) announces an independent scientific peer review panel meeting to evaluate modifications and new applications for the Murine Local Lymph Node Assay (LLNA). The LLNA is an alternative test method that can be used to determine the allergic contact dermatitis potential of chemicals and products. The panel will review the following:
- The validation status of three modified LLNA test method protocols that use non-radioactive probe chemicals.
- The validation status of a LLNA limit dose procedure.
- The use of the LLNA to test mixtures, aqueous solutions, and metals (applicability domain for the LLNA).
- The use of the LLNA to determine potency (potential for causing allergic contact dermatitis).
- Revised draft recommended performance standards for the LLNA.
At this meeting, the panel will peer review the draft background review documents and revised draft LLNA performance standards for each topic and evaluate the extent that established validation and acceptance criteria have been appropriately addressed. The panel will also comment on the extent Start Printed Page 1361that the review documents support draft ICCVAM recommendations on proposed test method protocols, proposed uses of the LLNA, and the revised draft LLNA performance standards.
NICEATM invites public comments on the draft background review documents, draft ICCVAM test recommendations, draft test method protocols, and revised draft LLNA performance standards. All documents will be available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/immunotox.htm by January 8, 2008.
The meeting is scheduled for March 4-6, 2008, from 8:30 a.m. to 5 p.m. each day. The meeting is open to the public free of charge, with attendance limited only by the space available. In order to facilitate planning for this meeting, persons wishing to attend are asked to register by February 20, 2008, via the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/contact/reg_LLNAPanel.htm). The deadline for written comments is February 22, 2008.
The meeting will be held at the U.S. Consumer Product Safety Commission (CPSC) Headquarters, Bethesda Towers Bldg., 4330 East West Highway, Bethesda, MD.Start Further Info
FOR FURTHER INFORMATION CONTACT:
Comments may also be submitted via the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm. Comments or other correspondence can be sent 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) firstname.lastname@example.org. Courier address: NICEATM, 79 T.W. Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 27709.End Further Info End Preamble Start Supplemental Information
The LLNA is a reduction and refinement alternative test method for skin sensitization testing because it reduces the number of animals needed and can substantially reduce or avoid pain and distress compared to traditional guinea pig testing methods for sensitization. The LLNA was the first alternative test method evaluated and recommended by ICCVAM (NIH Publication No. 99-4494, available at: http://iccvam.niehs.nih.gov/docs/immunotox_docs/llna/llnarep.pdf). Based on the recommendations of ICCVAM and an independent scientific peer review panel, U.S. and international regulatory authorities have accepted the LLNA as an alternative to the guinea pig maximization test and Buehler test for assessing allergic contact dermatitis (ISO 2002; OECD 2002; EPA 2003). This review will evaluate the potential for broader use of the LLNA for regulatory testing of chemicals and products for allergic contact dermatitis potential, enabling further reduction and refinement (less pain and suffering) of animal use for this purpose. In January 2007, the CPSC submitted a nomination requesting that NICEATM and ICCVAM assess the validation status of (1) the LLNA as a stand-alone assay for potency determination for hazard classification purposes; (2) modified LLNA protocols; (3) the LLNA limit test; (4) the use of the LLNA to test mixtures, aqueous solutions, and metals; and (5) the applicability domain for the LLNA. In June 2007, the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM) endorsed these activities as high priorities for ICCVAM. NICEATM on behalf of ICCVAM also sought input from the public on these activities (Federal Register: Vol. 72, No. 95, pages 27815-27817, May 17, 2007). After considering these inputs, ICCVAM endorsed these activities as high priorities. ICCVAM is also developing performance standards to facilitate evaluation of modified LLNA protocols compared to the traditional LLNA. Although ICCVAM has routinely developed performance standards for test methods since 2003, they were not developed as part of the ICCVAM evaluation of the LLNA in 1998. These draft performance standards for the LLNA were made public and comments were requested via the Federal Register (Vol. 72, No. 176, pages 52130-52131, Sept. 12, 2007). The May 2007 Federal Register notice requested data from studies using the LLNA or modified versions of the LLNA.
Drawing on the submitted data and literature sources, ICCVAM and NICEATM drafted background review documents for each of the modifications and new applications of the LLNA. ICCVAM has also developed draft test method recommendations regarding the proposed usefulness, limitations, and validation status of these test methods. ICCVAM will convene an independent scientific panel to peer review the draft background review documents for the test methods and determine whether the data and analyses in the draft documents support the draft ICCVAM test method recommendations. The panel will also be asked to comment on the adequacy of the revised draft performance standards, proposed future studies, draft standardized test method protocols, and recommended reference substances. NICEATM will ask the panel to consider all available information, including the scientific studies cited in the draft review documents, public comments, and any new information identified during the peer review, for developing their conclusions and recommendations.
Peer Review Panel Meeting
The purpose of this meeting is to conduct a scientific peer review of the revised draft performance standards and an evaluation of modifications and new applications for the LLNA. The LLNA is an alternative test method that can be used to determine the allergic contact dermatitis potential of chemicals and products. The panel will review the following:
- The LLNA as a stand-alone assay for potency determination for hazard classification purposes
- Modified LLNA protocols
- The LLNA limit test
- The use of the LLNA to test mixtures, aqueous solutions, and metals (applicability domain for the LLNA)
- The use of the LLNA to determine potency (potential for causing allergic contact dermatitis).
The panel will consider the draft background review documents for each of these methods and evaluate the extent that established validation and acceptance criteria are appropriately addressed for each test method (as described in the ICCVAM document, 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. 97-981, available at http://iccvam.niehs.nih.gov/docs/about_docs/validate.pdf). The panel will then comment on the extent to which the draft ICCVAM recommendations are supported by the information provided in the background review document for each topic. It is anticipated that the panel will address the topics in the following order:
1. The LLNA limit test.
2. The applicability domain of the LLNA including its suitability for mixtures, aqueous solutions, and metals.
3. The LLNA as a stand-alone assay for potency determination for hazard classification.
4. The revised draft performance standards for the LLNA.
5. The modified LLNA test method protocols using non-radioactive materials. Start Printed Page 1362
Additional information about the meeting, including a roster of the panel members and the draft agenda, will be made available two weeks prior to the meeting on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov). This information will also be available after that date by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT above).
Attendance and Registration
This public meeting will take place March 4-6, 2008, at the CPSC Headquarters, Bethesda Towers Bldg., 4330 East West Highway, Bethesda, MD (an area map, driving directions, and CPSC contact information are available at http://www.cpsc.gov/about/contact.html). The meeting will begin at 8:30 a.m. and is scheduled to conclude at approximately 5 p.m. each day, although adjournment on March 6 may occur earlier or later depending upon the time needed for the expert panel to complete its work. It is also possible that the panel may conclude its deliberations on March 5 and not need to meet on March 6. Persons needing special assistance in order to attend, such as sign language interpretation or other reasonable accommodation, should contact 919-541-2475 (voice), 919-541-4644 TTY (text telephone, through the Federal TTY Relay System at 800-877-8339), or e-mail email@example.com. Requests should be made at least seven days in advance of the event.
Availability of the Draft Background Review Documents and Draft ICCVAM Recommendations
NICEATM prepared draft background review documents on each of these modifications or applications of the LLNA that describe the current validation status of the modified test methods and applications and contain all of the data and analyses supporting this proposed validation status. The draft background review documents, draft ICCVAM test method recommendations, draft test method protocols, and revised draft test method performance standards are available from the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/methods/immunotox/immunotox.htm) or by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT above).
Request for Public Comments
NICEATM invites the submission of written comments on the draft background review documents, draft ICCVAM test method recommendations, draft test method protocols, and revised draft test method performance standards. Written comments should be submitted preferably electronically via the NICEATM-ICCVAM Web site or by e-mail (firstname.lastname@example.org); the deadline for submission of written comments is February 22, 2008. When submitting written comments, please refer to this Federal Register notice and include appropriate contact information (name, affiliation, mailing address, phone, fax, e-mail, and sponsoring organization, if applicable). Written comments may also be sent by mail, fax, or e-mail to Dr. William Stokes (see FOR FURTHER INFORMATION CONTACT above). All comments received will be placed on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov) and identified by the individual's name and affiliation or sponsoring organization (if applicable). Comments will also be sent to the panel and ICCVAM agency representatives and made available at the meeting.
This meeting is open to the public, and time will be provided for the presentation of oral comments by the public at designated times during the peer review. Members of the public who wish to present oral statements at the meeting should contact NICEATM (see FOR FURTHER INFORMATION CONTACT above) no later than February 20, 2008, and provide contact information (name, affiliation, mailing address, phone, fax, e-mail, and sponsoring organization, if applicable). Up to seven minutes will be allotted per speaker, one speaker per organization. Persons registering to make comments are asked to provide NICEATM a written copy of their statement by February 27, 2008, so that copies can be distributed to the panel prior to the meeting. If this is not possible, please bring 40 copies of your comments to the meeting for distribution and to supplement the record. Written statements can supplement and expand the oral presentation.
Summary minutes and the panel's final report will be available following the meeting on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov). ICCVAM will consider the panel's conclusions and recommendations and any public comments received when finalizing their test method recommendations and performance standards for these methods.
Background Information on ICCVAM and NICEATM
ICCVAM is an interagency committee composed of representatives from 15 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 and that refine, reduce, or replace animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3, available at http://iccvam.niehs.nih.gov/docs/about_docs/PL106545.pdf) establishes ICCVAM as a permanent interagency committee of the NIEHS under NICEATM. NICEATM administers 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 Federal agencies. Additional information about ICCVAM and NICEATM is available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov.
EPA. 2003. EPA OPPTS 870.2600 Test Guideline—Skin Sensitization. Available: http://www.epa.gov/opptsfrs/publications/OPPTS_Harmonized/870_Health_Effects_Test_Guidelines/Drafts/870-2600.pdf.
ISO. 2002. ISO 10993-10 Biological evaluation of medical devices—Part 10: Tests for irritation and delayed-type hypersensitivity. Geneva: International Organization for Standardization.
OECD. 2002. OECD Guideline for the Testing of Chemicals—Test Guideline 429: Skin Sensitization: Local Lymph Node Assay (adopted 24 April 2002). Paris: Organisation for Economic Co-operation and Development.Start Signature
Dated: December 19, 2007.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences and National Toxicology Program.
[FR Doc. E7-25553 Filed 1-7-08; 2:42 pm]
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