[Federal Register Volume 73, Number 5 (Tuesday, January 8, 2008)]
[Notices]
[Pages 1360-1362]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-25553]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Toxicology Program (NTP); NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Announcement 
of an Independent Scientific Peer Review Panel Meeting on the Murine 
Local Lymph Node Assay; Availability of Draft Background Review 
Documents; Request for Comments

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

ACTION: Meeting announcement and request for comments.

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SUMMARY: 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

[[Page 1361]]

that 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.

DATES: 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.

ADDRESSES: The meeting will be held at the U.S. Consumer Product Safety 
Commission (CPSC) Headquarters, Bethesda Towers Bldg., 4330 East West 
Highway, Bethesda, MD.

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) [email protected]. Courier address: NICEATM, 79 T.W. 
Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 
27709.

SUPPLEMENTARY INFORMATION: 

Background

    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.

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    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 protected]. 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 
([email protected]); 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.

References

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.

    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]
BILLING CODE 4140-01-P