[Federal Register Volume 75, Number 89 (Monday, May 10, 2010)]
[Notices]
[Pages 25866-25867]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-10954]
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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); Federal
Agency Responses to Interagency Coordinating Committee on the
Validation of Alternative Methods Recommendations on the Murine Local
Lymph Node Assay, An Alternative Test Method for Assessing the Allergic
Contact Dermatitis Potential of Chemicals and Products: Notice of
Availability
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH).
ACTION: Notice of Availability.
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SUMMARY: U.S. Federal agency responses to Interagency Coordinating
Committee on the Validation of Alternative Methods (ICCVAM) test method
recommendations on the murine local lymph node assay (LLNA), an
alternative safety testing method used to assess the potential of
chemicals and products to cause allergic contact dermatitis (ACD), are
now available. ICCVAM recommended an updated LLNA test method protocol,
a reduced LLNA procedure (rLLNA), and LLNA test method performance
standards. In accordance with the ICCVAM Authorization Act, ICCVAM
previously forwarded recommendations to Federal agencies and made these
recommendations available to the public (74 FR 50212). Agencies have
now notified ICCVAM in writing of their findings and ICCVAM is making
these responses available to the public. Federal agency responses are
available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/rLLNA.htm and http://iccvam.niehs.nih.gov/methods/immunotox/llna_PerfStds.htm. The ICCVAM
recommendations are provided in ICCVAM Test Method Evaluation Reports,
which are available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-LD/TMER.htm and http://iccvam.niehs.nih.gov/methods/immunotox/PerfStds/llna-ps.htm.
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)
[email protected]. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
[[Page 25867]]
Background
ICCVAM originally recommended the LLNA as a valid stand-alone
alternative method to existing ACD test methods in 1999 (NIH
publication No. 99-4494; available at http://iccvam.niehs.nih.gov/docs/immunotox_docs/llna/llnarep.pdf). ICCVAM recommended that the LLNA
could be used as a substitute for the existing guinea pig based test
methods for most testing situations, which would reduce the number of
animals required and avoid pain and distress. The Environmental
Protection Agency (EPA), the Food and Drug Administration (FDA), and
the Consumer Product Safety Commission (CPSC) subsequently accepted the
method as a valid substitute. The Organization for Economic Co-
operation and Development (OECD) adopted the LLNA as international OECD
Test Guideline 429 and the International Standards Organization (ISO)
adopted the LLNA as ISO Test 10993-10.
The updated LLNA test method protocol uses 20% fewer animals than
the original LLNA protocol recommended by ICCVAM in 1999, and provides
improved guidance on dose selection and other procedures to improve
assay accuracy and reproducibility. The rLLNA procedure can further
reduce the number of animals required by 40% compared to the updated
LLNA protocol multi-dose procedure. ICCVAM recommends that the rLLNA
test method should be routinely considered before conducting the
traditional multi-dose LLNA, and should be used as the initial test for
ACD where determined appropriate. ICCVAM evaluation and complete
recommendations for the updated LLNA test method protocol and the rLLNA
procedure are provided in 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 No. 09-6439, available at
http://iccvam.niehs.nih.gov/methods/immunotox/LLNA-LD/TMER.htm).
ICCVAM also recommends that the LLNA test method performance
standards can be used to efficiently evaluate the validity of modified
test methods that are mechanistically and functionally similar to the
traditional LLNA. The LLNA test method performance standards are
provided in the ICCVAM report, Recommended Performance Standards:
Murine Local Lymph Node Assay (NIH Publication No. 09-7357, available
at http://iccvam.niehs.nih.gov/methods/immunotox/PerfStds/llna-ps.htm).
ICCVAM evaluated the updated versions of the LLNA in response to a
2007 nomination from the CPSC (http://iccvam.niehs.nih.gov/methods/immunotox/llnadocs/CPSC_LLNA_nom.pdf). The nomination also requested
that ICCVAM evaluate the validation status of (1) new versions of the
LLNA test method protocol that do not require the use of radioactive
materials; (2) use of the LLNA to test mixtures, aqueous solutions,
metals, and other substances; and (3) use of the LLNA to determine ACD
potency categories for hazard classification and labeling purposes.
ICCVAM recommendations on these new versions and applications are
undergoing finalization and will be forwarded to Federal agencies in
2010.
Agency Reponses to ICCVAM Recommendations
In September 2009, ICCVAM forwarded final test method
recommendations for the rLLNA, the updated LLNA test method protocol,
and LLNA performance standards to U.S. Federal agencies for
consideration, in accordance with the ICCVAM Authorization Act of 2000
(42 U.S.C. 285l-3(e)(4)) (74 FR 50212). The ICCVAM Authorization Act
requires member agencies to review ICCVAM test method recommendations
and notify ICCVAM in writing of their findings no later than 180 days
after receipt of recommendations. The Act also requires ICCVAM to make
ICCVAM recommendations and agency responses available to the public.
Agency responses are to include identification of relevant test methods
for which the ICCVAM test method recommendations may be added or
substituted, and indicate any revisions or planned revisions to
existing guidelines, guidances, or regulations to be made in response
to these recommendations.
Background Information on ICCVAM and NICEATM
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).
Dated: April 30, 2010.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2010-10954 Filed 5-7-10; 8:45 am]
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