[Federal Register: January 8, 2008 (Volume 73, Number 5)]
[Notices]
[Page 1360-1362]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08ja08-76]
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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) niceatm@niehs.nih.gov. 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.
[[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 niehsoeeo@niehs.nih.gov. 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
niceatm@niehs.nih.gov); 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