[Federal Register: September 30, 2009 (Volume 74, Number 188)]
[Notices]
[Page 50212-50213]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr30se09-61]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Toxicology Program (NTP); NTP Interagency Center for the
Evaluation of Alternative Toxicological Methods (NICEATM); Availability
of the Interagency Coordinating Committee on the Validation of
Alternative Methods (ICCVAM) Test Method Evaluation Report: The Reduced
Murine Local Lymph Node Assay, an Alternative Test Method Using Fewer
Animals To Assess the Allergic Contact Dermatitis Potential of
Chemicals and Products; Availability of ICCVAM Recommended Murine Local
Lymph Node Assay Performance Standards; Notice of Transmittal to
Federal Agencies of ICCVAM Test Method Recommendations for the Reduced
Murine Local Lymph Node Assay, Updated Murine Local Lymph Node Assay
Test Method Protocol, and Murine Local Lymph Node Assay Test Method
Performance Standards
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH)
ACTION: Availability of ICCVAM Test Method Evaluation Report (TMER) and
Recommended Test Method Performance Standards; Notice of Transmittal.
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SUMMARY: NICEATM announces availability of the ICCVAM Test Method
Evaluation Report: The Reduced Murine Local Lymph Node Assay: An
Alternative Test Method Using Fewer Animals to Assess the Allergic
Contact Dermatitis Potential of Chemicals and Products (NIH Publication
09-6439). The TMER provides ICCVAM's evaluation and recommendations for
the reduced Murine Local Lymph Node Assay (rLLNA) test method as a
reduction alternative that uses fewer animals compared to the
traditional Murine Local Lymph Node Assay (LLNA) for assessing the
potential of test substances to cause allergic contact dermatitis
(ACD). The report includes ICCVAM's recommendations on (a) the
usefulness and limitations of the rLLNA, (b) an updated ICCVAM LLNA
test method protocol, which includes the procedures for conducting the
rLLNA, (c) future studies to further characterize the usefulness and
limitations of the rLLNA, and (d) rLLNA test method performance
standards. The TMER includes the report of an international independent
scientific peer review panel (hereafter, Panel) and the final rLLNA
background review document (BRD). The BRD provides the data and
analyses used to evaluate the current validation status of the rLLNA
test method for assessing the ACD potential of chemicals and products.
ICCVAM concluded that the scientific validity of the rLLNA has been
adequately evaluated and that the performance of the rLLNA, when
conducted in accordance with the ICCVAM-recommended LLNA test method
protocol, is sufficient to distinguish between skin sensitizers and
non-sensitizers. ICCVAM also concluded that the rLLNA would reduce
animal use by 40% for each test compared to the traditional, multi-dose
LLNA. Accordingly, ICCVAM recommends that the rLLNA test method should
be routinely considered before conducting the traditional, multi-dose
LLNA, and used where appropriate as the initial test to determine the
potential of chemicals and products to produce ACD. For testing
situations that require dose-response information, rLLNA-positive
substances will need to be tested with the traditional multi-dose LLNA.
This testing should be done using the updated ICCVAM-recommended test
method protocol, which reduces animal use by 20% compared to the
original ICCVAM-recommended test method protocol by decreasing the
minimum number of animals per dose group from five to four.
NICEATM also announces availability of the ICCVAM Recommended
Performance Standards: Murine Local Lymph Node Assay (NIH Publication
09-7357). The ICCVAM recommends that LLNA test method performance
standards can be used to efficiently evaluate the validity of modified
versions of the LLNA that are mechanistically and functionally similar
to the traditional LLNA. The traditional LLNA test method is the
reference test method used as the basis for establishing the LLNA
performance standards. The performance standards specify the essential
test method components that must be included in a modified LLNA in
order to use the performance standards to evaluate the validity of the
modified test method. The performance standards also specify a minimum
list of reference substances to evaluate the accuracy and reliability
of the modified test method, and the accuracy and reliability values
that must be achieved in order for the modified test method to be
considered equal to or better than the traditional LLNA.
Electronic copies of the ICCVAM rLLNA TMER and the report on
ICCVAM-recommended LLNA performance standards are available from the
NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov or by contacting
NICEATM (see FOR FURTHER INFORMATION CONTACT). The two reports have
been forwarded to U.S. Federal agencies for regulatory and other
acceptance considerations, where applicable. Responses will be posted
on the NICEATM-ICCVAM website as they are received.
FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director,
NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle
Park, NC 27709, (telephone) 919-541-2384, (fax) 919-541-0947, (e-mail)
niceatm@niehs.nih.gov. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
Background
The U.S. Consumer Product Safety Commission (CPSC) nominated
several new versions and applications of the LLNA to ICCVAM in 2007 for
evaluation of their scientific validity (http://iccvam.niehs.nih.gov/
methods/immunotox/llnadocs/CPSC_LLNA_nom.pdf). The nomination
requested that ICCVAM assess the validation status of: (1) the LLNA
limit dose procedure (i.e., the rLLNA); (2) three modified LLNA test
method protocols that do not require the use of radioactive materials;
(3) the use of the LLNA to test mixtures, aqueous solutions, and metals
(applicability domain for the LLNA); and (4) the use of the LLNA to
determine ACD potency categories for hazard classification. NICEATM
published a Federal Register notice (72 FR 27815) requesting public
comments on the appropriateness and relative priority of the CPSC-
nominated LLNA activities, the development of test method performance
standards for the LLNA, the nomination of scientists to serve on the
Panel, and the submission of data from LLNA testing that related to the
CPSC-nominated LLNA activities, as well as corresponding data from
human and other animal studies. After considering public comments and
comments from the Scientific Advisory Committee on Alternative
Toxicological
[[Page 50213]]
Methods (SACATM), ICCVAM unanimously endorsed the nomination with a
high priority. ICCVAM and NICEATM began evaluation activities and also
initiated development of proposed test method performance standards for
the LLNA since these had not previously been developed (http://
iccvam.niehs.nih.gov/methods/immunotox/immunotox.htm). NICEATM and
ICCVAM compiled a comprehensive draft BRD on the rLLNA test method and
a draft test method performance standards document for the LLNA and
released them for public comment in January 2008 (73 FR 1360).
NICEATM and ICCVAM convened the Panel at a meeting on March 4-6,
2008, to review the draft BRDs and evaluate the validation status of
the proposed test methods and applications. The Panel also reviewed the
extent that the information contained in the draft BRDs supported draft
ICCVAM test method recommendations for test method uses and
limitations, updated standardized test method protocols, and proposed
future studies. The Panel reviewed the draft ICCVAM LLNA test method
performance standards for their adequacy for assessing the accuracy and
reliability of test method protocols that are based on similar
scientific principles and that measure the same biological effect as
the traditional LLNA. The Panel considered public comments made at the
meeting as well as public comments submitted in advance of the meeting,
before concluding their deliberations. The Panel's report was made
available in May 2008 (73 FR 29136) for public comment. The draft
ICCVAM BRDs, draft ICCVAM test method recommendations, draft ICCVAM
LLNA test method performance standards, the Panel's report, and all
public comments were made available to the SACATM for comment on June
18-19, 2008 (73 FR 25754).
ICCVAM considered the Panel's report, all public comments, and
SACATM comments in finalizing its recommendations for the rLLNA, the
updated LLNA test method protocol, and LLNA test method performance
standards. ICCVAM has forwarded its test method recommendations to U.S.
Federal agencies for consideration, in accordance with the ICCVAM
Authorization Act of 2000 (42 U.S.C. 285l-3(e)(4)). Agency responses to
the ICCVAM test method recommendations will be made available on the
NICEATM-ICCVAM Web site as they are received.
Background Information on ICCVAM, NICEATM, and SACATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that use, generate, or
disseminate 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, and replace animal use. The ICCVAM Authorization Act of 2000
established 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 U.S. Federal agencies. Additional
information about ICCVAM and NICEATM can be found on their Web site
(http://www.iccvam.niehs.nih.gov).
SACATM was established January 9, 2002, and is composed of
scientists from the public and private sectors (67 FR 11358). SACATM
provides advice to the Director of the NIEHS, ICCVAM, and NICEATM
regarding the statutorily-mandated duties of ICCVAM and activities of
NICEATM. Additional information about SACATM, including the charter,
roster, and records of past meetings, can be found at http://
ntp.niehs.nih.gov/go/167.
Dated: September 22, 2009.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. E9-23534 Filed 9-29-09; 8:45 am]
BILLING CODE 4140-01-P