National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Availability of Interagency Coordinating Committee on the Validation of Alternative Methods Test Method Evaluation Reports on Two Nonradioactive Versions of the Murine Local Lymph Node Assay for Assessing Allergic Contact Dermatitis Hazard Potential of Chemicals and Products, and Expanded Uses of the Local Lymph Node Assay for Pesticide Formulations and Other Products; Notice of Transmittal to Federal Agencies, 37443-37445 [2010-15777]
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Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Toxicology Program (NTP);
NTP Interagency Center for the
Evaluation of Alternative Toxicological
Methods (NICEATM); Availability of
Interagency Coordinating Committee
on the Validation of Alternative
Methods Test Method Evaluation
Reports on Two Nonradioactive
Versions of the Murine Local Lymph
Node Assay for Assessing Allergic
Contact Dermatitis Hazard Potential of
Chemicals and Products, and
Expanded Uses of the Local Lymph
Node Assay for Pesticide Formulations
and Other Products; Notice of
Transmittal to Federal Agencies
emcdonald on DSK2BSOYB1PROD with NOTICES4
AGENCY: National Institute of
Environmental Health Sciences
(NIEHS), National Institutes of Health
(NIH), HHS.
ACTION: Availability of Reports; Notice
of Transmittal.
SUMMARY: NICEATM announces
availability of Interagency Coordinating
Committee on the Validation of
Alternative Methods (ICCVAM) Test
Method Evaluation Reports (TMERs)
recommending two nonradioactive
versions of the Local Lymph Node
Assay (LLNA) for assessing allergic
contact dermatitis (ACD) hazard
potential of chemicals and products and
expanded uses of the LLNA for
pesticide formulations and other
products. Related ICCVAM Test Method
Recommendations in each report have
also been transmitted to Federal
agencies for their review and response
to ICCVAM in accordance with the
provisions of the ICCVAM
Authorization Act of 2000. The LLNA:
5-Bromo-2′-deoxyuridine-EnzymeLinked Immunosorbent Assay (BrdUELISA) and LLNA: Daicel Adenosine
Triphosphate (DA) do not use
radioactive reagents and therefore
provide advantages in terms of reduced
hazardous waste disposal and broader
availability for use by laboratories that
cannot use radioactive reagents.
ICCVAM concludes that the accuracy
and reliability of the LLNA: BrdUELISA and LLNA: DA support use of
these test methods to identify
substances as potential skin sensitizers
or nonsensitizers. Based on an updated
evaluation, ICCVAM is also
recommending expanded use of the
LLNA to evaluate the ACD hazard
potential of pesticide formulations and
other products.
FOR FURTHER INFORMATION CONTACT: Dr.
William S. Stokes, Director, NICEATM,
NIEHS, P.O. Box 12233, Mail Stop: K2–
VerDate Mar<15>2010
19:55 Jun 28, 2010
Jkt 220001
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
ICCVAM previously evaluated the
validation status of the LLNA as a standalone alternative method to the guinea
pig maximization test (GPMT) and the
Buehler test (BT) for assessing the ACD
hazard potential of products and
chemicals (NIH Publication No. 99–
4494; available at https://
iccvam.niehs.nih.gov/methods/
immunotox/llna.htm). Based on this
evaluation, ICCVAM recommended the
LLNA as a valid substitute for the
guinea pig test methods for most testing
situations in 1999. The Environmental
Protection Agency, the Food and Drug
Administration, and the U.S. Consumer
Product Safety Commission (CPSC)
subsequently accepted the method as a
valid substitute for the GPMT and BT.
The Organization for Economic Cooperation and Development (OECD)
subsequently adopted the LLNA as
OECD Test Guideline 429 in 2002.
Using the LLNA instead of guinea pig
tests reduces and refines (less pain and
distress) animal use for ACD safety
testing.
In 2007, the CPSC nominated several
new versions and applications of the
LLNA to ICCVAM for evaluation of their
scientific validity (https://
iccvam.niehs.nih.gov/methods/
immunotox/llnadocs/
CPSC_LLNA_nom.pdf). The nomination
requested that ICCVAM assess (1) the
validation status of the LLNA limit dose
procedure (i.e., the reduced LLNA); (2)
the 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; 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 (1) the appropriateness
and relative priority of the CPSCnominated LLNA activities, (2) the
nomination of scientists to serve on an
international independent scientific
peer review panel, and (3) 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. ICCVAM assigned
these activities a high priority after
considering comments from the public
PO 00000
Frm 00069
Fmt 4703
Sfmt 4703
37443
and endorsement from the Scientific
Advisory Committee on Alternative
Toxicological Methods (SACATM).
NICEATM and ICCVAM compiled
comprehensive draft background review
documents (BRDs), released them for
public comment in January 2008 (73 FR
1360), and convened a public meeting of
the panel on March 4–6, 2008 to peer
review the draft documents. The panel
evaluated the information in the BRDs
as to whether it supported draft
ICCVAM test method recommendations
for test method uses and limitations,
updated standardized test method
protocols, and proposed future studies.
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, the panel’s
report, and all public comments were
made available to SACATM for
comment at its meeting on June 18–19,
2008 (73 FR 25754).
After considering the conclusions and
recommendations of the panel,
comments from SACATM, and public
comments, ICCVAM forwarded final
recommendations for the updated LLNA
test method protocol, the reduced
LLNA, and LLNA performance
standards to Federal agencies in
September 2009 (74 FR 50212).
ICCVAM concluded that the updated
LLNA test method protocol will further
reduce animal use by 20% compared to
the original version of the LLNA and
also provide for more consistent and
reliable results. The reduced LLNA will
reduce animal use by 40% for each test
compared to the traditional, multi-dose
LLNA. ICCVAM also recommended
LLNA test method performance
standards that can be used to efficiently
evaluate the validity of modified
versions of the LLNA that are
mechanistically and functionally similar
to the traditional LLNA. Federal
agencies subsequently responded with
their support and concurrence with the
ICCVAM recommendations. Agency
responses are available on the
NICEATM–ICCVAM Web site.
NICEATM subsequently obtained
additional data and/or information and
revised the draft documents for both the
traditional and nonradioactive LLNA
methods. ICCVAM released the revised
draft documents to the public for
comment and announced a second
meeting of the panel (74 FR 8974). The
panel reconvened in public session on
April 28–29, 2009 to review the
ICCVAM-revised draft documents and
E:\FR\FM\29JNN1.SGM
29JNN1
emcdonald on DSK2BSOYB1PROD with NOTICES4
37444
Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Notices
finalize its conclusions and
recommendations on the current
validation status of the nonradioactive
test methods and the expanded uses of
the LLNA for pesticide formulations and
other products. The panel’s report was
made available for public comment in
June 2009 (74 FR 26242). The revised
draft ICCVAM BRDs, revised draft
ICCVAM test method recommendations,
the panel’s report, and all public
comments were made available to
SACATM for comment on June 25–26,
2009 (74 FR 19562). After considering
the conclusions and recommendations
of the panel, comments from SACATM,
and public comments, along with the
recommendations of an OECD Expert
Consultation on the LLNA convened in
October and December 2009, ICCVAM
finalized and forwarded test method
recommendations to Federal agencies
for their 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
website as they are received.
The ICCVAM TMERs, The LLNA:
BrdU–ELISA, A Nonradioactive
Alternative Test Method to Assess the
Allergic Contact Dermatitis Potential of
Chemicals and Products (NIH
Publication 10–7552), and The LLNA:
DA, A Nonradioactive Alternative Test
Method to Assess the Allergic Contact
Dermatitis Potential of Chemicals and
Products (NIH Publication 10–7551),
describe ICCVAM’s recommendations
for using the LLNA: BrdU–ELISA and
LLNA: DA for regulatory hazard
identification purposes. The reports also
provide ICCVAM-recommended LLNA:
BrdU–ELISA and LLNA: DA test
method protocols, the final BRDs, and
the peer review reports of the panel. The
ICCVAM-recommended LLNA: BrdU–
ELISA test method protocol is based on
the protocol developed by Takeyoshi et
al. (2001). The ICCVAM-recommended
LLNA: DA test method protocol is based
on the protocol developed by Idehara et
al. (2008). Both test method protocols
incorporate all relevant aspects of the
recently updated ICCVAMrecommended traditional LLNA test
method protocol (ICCVAM, 2009). The
protocols also include reduced LLNA:
BrdU–ELISA and LLNA: DA procedures
that should always be considered and
used where determined appropriate in
order to further reduce animal use.
The ICCVAM Test Method Evaluation
Report, Using the Murine Local Lymph
Node Assay for Testing Pesticide
Formulations, Metals, Substances in
Aqueous Solutions, and Other Products
(NIH Publication 10–7512) provides
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19:55 Jun 28, 2010
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ICCVAM’s updated evaluation and
recommendations for use of the LLNA
to evaluate the ACD hazard potential of
pesticide formulations, metals,
substances in aqueous solutions, and
other products. The evaluation
considered new data that became
available subsequent to the original
ICCVAM LLNA evaluation in 1999. The
report also includes the peer review
reports of the panel.
ICCVAM’s evaluation of the LLNA for
skin sensitization potency
categorization is currently nearing
completion, and final ICCVAM
recommendations will be forwarded to
Federal agencies later this year.
Background Information on ICCVAM,
NICEATM, and SACATM
ICCVAM is an interagency committee
composed of representatives from 15
Federal regulatory and research agencies
that require, 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 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 (42 U.S.C 285l3). 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.
NICEATM and ICCVAM welcome the
public nomination of new, revised, and
alternative test methods for both
validation studies as well as technical
evaluations. Additional information
about ICCVAM and NICEATM can be
found on the NICEATM–ICCVAM Web
site (https://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 statutorilymandated duties of ICCVAM and
activities of NICEATM. Additional
information about SACATM, including
the charter, roster, and records of past
meetings, can be found at https://
ntp.niehs.nih.gov/go/167.
References
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report on The LLNA: BrdU–
ELISA, A Nonradioactive Alternative
PO 00000
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Fmt 4703
Sfmt 4703
Test Method to Assess the Allergic
Contact Dermatitis Potential of
Chemicals and Products. NIH
Publication Number 10–7552. Research
Triangle Park, NC: National Institute of
Environmental Health Sciences.
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report on The LLNA: DA, A
Nonradioactive Alternative Test Method
to Assess the Allergic Contact
Dermatitis Potential of Chemicals and
Products. NIH Publication Number 10–
7551. Research Triangle Park, NC:
National Institute of Environmental
Health Sciences.
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report on Using the Murine
Local Lymph Node Assay for Testing
Pesticide Formulations, Metals,
Substances in Aqueous Solutions, and
Other Products. NIH Publication
Number 10–7512. Research Triangle
Park, NC: National Institute of
Environmental Health Sciences.
ICCVAM. 2009. Recommended
Performance Standards: Murine Local
Lymph Node Assay. NIH Publication
Number 09–7357. Research Triangle
Park, NC: National Institute of
Environmental Health Sciences.
Available at: https://
iccvam.niehs.nih.gov/methods/
immunotox/llna_PerfStds.htm.
ICCVAM. 2009. 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 Number 09–
6439. Research Triangle Park, NC:
National Institute of Environmental
Health Sciences. Available at: https://
iccvam.niehs.nih.gov/methods/
immunotox/LLNA–LD/TMER.htm.
ICCVAM. 1999. The Murine Local
Lymph Node Assay: A Test Method for
Assessing the Allergic Contact
Dermatitis Potential of Chemicals/
Compounds. The Results of an
Independent Peer Review Evaluation
Coordinated by ICCVAM and
NICEATM. NIH Publication Number
99–4494. Research Triangle Park, NC:
National Institute of Environmental
Health Sciences. Available at: https://
iccvam.niehs.nih.gov/methods/
immunotox/llna.htm.
Idehara K, Yamagishi G, Yamashita K,
Ito M. 2008. Characterization and
evaluation of a modified local lymph
node assay using ATP content as a nonradio isotopic endpoint. Journal of
Pharmacological and Toxicological
Methods 58(1): 1–10.
Takeyoshi M, Yamasaki K, Yakabe Y,
Takatsuki M, Kimber I. 2001.
Development of non-radio isotopic
endpoint of murine local lymph node
E:\FR\FM\29JNN1.SGM
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37445
Federal Register / Vol. 75, No. 124 / Tuesday, June 29, 2010 / Notices
assay based on 5-bromo-2’-deoxyuridine
(BrdU) incorporation. Toxicology
Letters 119(3): 203–208.
Dated: June 16, 2010.
John R. Bucher,
Associate Director, National Toxicology
Program.
[FR Doc. 2010–15777 Filed 6–28–10; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Disease Control and
Prevention
[30Day–10–09CJ]
Agency Forms Undergoing Paperwork
Reduction Act Review
The Centers for Disease Control and
Prevention (CDC) publishes a list of
information collection requests under
review by the Office of Management and
Budget (OMB) in compliance with the
Paperwork Reduction Act (44 U.S.C.
Chapter 35). To request a copy of these
requests, call the CDC Reports Clearance
Officer at (404) 639–5960 or send an
e-mail to omb@cdc.gov. Send written
comments to CDC Desk Officer, Office of
Management and Budget, Washington,
DC, or by fax to (202) 395–5806. Written
comments should be received within 30
days of this notice.
interviews with 20 non-Hispanic black,
heterosexual men, ages 18–25, who
were recently arrested or who were
recently released from jail/prison and
meet screening criteria. The interviews
will identify their attitudes towards HIV
testing, socio-cultural norms, and
perceived behavioral control factors that
influence HIV testing. The interviews
will also elicit their opinions of how to
promote HIV testing among their peers.
Each interview will last approximately
1.5 hours. During Phase 2, the results
from Phase I will be used to identify
variables for a survey that will examine
attitudes towards HIV testing, sociocultural norms, and perceived
behavioral control factors to HIV testing
intentions and behaviors. The survey
will include 250 non-Hispanic black
heterosexual men, ages 18–25, who
meet screening criteria. Each survey will
last approximately 30 minutes.
During Phase 3, using Phase 1 and 2
results, educational materials promoting
HIV testing among 24 non-Hispanic
black heterosexual men will be
developed and pilot tested in focus
groups of young black men who meet
screening criteria to evaluate the
acceptability of the materials.
This study will provide important
epidemiologic information useful for the
development of HIV prevention
interventions for young black men.
There is no cost to respondents except
for their time. The estimated annualized
burden hours are 265.
Proposed Project
Promoting HIV Testing among Low
Income Heterosexual Young Adult
Black Men—New—National Center for
HIV/AIDS, Viral Hepatitis, STD, and TB
Prevention (NCHHSTP), Centers for
Disease Control and Prevention (CDC).
Background and Brief Description
The lifetime risk of acquiring HIV
infection for black men is 1 in 16.
Heterosexual transmission is the second
highest category for HIV infection
among black men, yet we know little
about how to successfully access
heterosexual black men with HIV
prevention and testing messages. CDC is
requesting OMB approval for 2 years to
collect data for this 3-phase study. The
data collection will take place in
Queens and Brooklyn, New York.
The purpose of the proposed study is
to elicit attitudes about HIV testing
among a community-based sample of
non-Hispanic black, heterosexual men,
ages 18–25, who were recently arrested
or who were recently released from
jail/prison. The study will develop
culturally-tailored and gender-specific
educational materials that promote HIV
testing among this population. The data
collection process will take
approximately 2 years.
There will be a screening for each
phase, 30 respondents for the one-onone, 300 respondents for the survey, and
40 for the focus group. In Phase 1, local
investigators will conduct qualitative
ESTIMATE OF ANNUALIZED BURDEN HOURS
Type of respondents
General
General
General
General
General
General
public
public
public
public
public
public
.................................................
.................................................
.................................................
.................................................
.................................................
.................................................
Dated: June 17, 2010.
Maryam I. Daneshvar,
Reports Clearance Officer, Centers for Disease
Control and Prevention.
[FR Doc. 2010–15782 Filed 6–28–10; 8:45 am]
emcdonald on DSK2BSOYB1PROD with NOTICES4
BILLING CODE 4163–18–P
Number of
respondents
Form name
Screener for one-on-one interviews ...............
One-on-one interviews ...................................
Screener for surveys ......................................
Surveys ..........................................................
Screener for focus groups .............................
Focus groups .................................................
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Substance Abuse and Mental Health
Services Administration
Agency Information Collection
Activities: Proposed Collection;
Comment Request
In compliance with Section
3506(c)(2)(A) of the Paperwork
Reduction Act of 1995 concerning
opportunity for public comment on
proposed collections of information, the
Substance Abuse and Mental Health
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30
20
300
250
40
24
Number of
responses per
respondents
1
1
1
1
1
1
Average
burden per
responses
(hours)
10/60
1.5
10/60
30/60
10/60
2
Services Administration will publish
periodic summaries of proposed
projects. To request more information
on the proposed projects or to obtain a
copy of the information collection
plans, call the SAMHSA Reports
Clearance Officer on (240) 276–1243.
Comments are invited on: (a) Whether
the proposed collections of information
are necessary for the proper
performance of the functions of the
agency, including whether the
information shall have practical utility;
(b) the accuracy of the agency’s estimate
of the burden of the proposed collection
E:\FR\FM\29JNN1.SGM
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]]>Agencies
[Federal Register Volume 75, Number 124 (Tuesday, June 29, 2010)]
[Notices]
[Pages 37443-37445]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-15777]
[[Page 37443]]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Toxicology Program (NTP); NTP Interagency Center for the
Evaluation of Alternative Toxicological Methods (NICEATM); Availability
of Interagency Coordinating Committee on the Validation of Alternative
Methods Test Method Evaluation Reports on Two Nonradioactive Versions
of the Murine Local Lymph Node Assay for Assessing Allergic Contact
Dermatitis Hazard Potential of Chemicals and Products, and Expanded
Uses of the Local Lymph Node Assay for Pesticide Formulations and Other
Products; Notice of Transmittal to Federal Agencies
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH), HHS.
ACTION: Availability of Reports; Notice of Transmittal.
-----------------------------------------------------------------------
SUMMARY: NICEATM announces availability of Interagency Coordinating
Committee on the Validation of Alternative Methods (ICCVAM) Test Method
Evaluation Reports (TMERs) recommending two nonradioactive versions of
the Local Lymph Node Assay (LLNA) for assessing allergic contact
dermatitis (ACD) hazard potential of chemicals and products and
expanded uses of the LLNA for pesticide formulations and other
products. Related ICCVAM Test Method Recommendations in each report
have also been transmitted to Federal agencies for their review and
response to ICCVAM in accordance with the provisions of the ICCVAM
Authorization Act of 2000. The LLNA: 5-Bromo-2'-deoxyuridine-Enzyme-
Linked Immunosorbent Assay (BrdU-ELISA) and LLNA: Daicel Adenosine
Triphosphate (DA) do not use radioactive reagents and therefore provide
advantages in terms of reduced hazardous waste disposal and broader
availability for use by laboratories that cannot use radioactive
reagents. ICCVAM concludes that the accuracy and reliability of the
LLNA: BrdU-ELISA and LLNA: DA support use of these test methods to
identify substances as potential skin sensitizers or nonsensitizers.
Based on an updated evaluation, ICCVAM is also recommending expanded
use of the LLNA to evaluate the ACD hazard potential of pesticide
formulations and other products.
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
ICCVAM previously evaluated the validation status of the LLNA as a
stand-alone alternative method to the guinea pig maximization test
(GPMT) and the Buehler test (BT) for assessing the ACD hazard potential
of products and chemicals (NIH Publication No. 99-4494; available at
https://iccvam.niehs.nih.gov/methods/immunotox/llna.htm). Based on this
evaluation, ICCVAM recommended the LLNA as a valid substitute for the
guinea pig test methods for most testing situations in 1999. The
Environmental Protection Agency, the Food and Drug Administration, and
the U.S. Consumer Product Safety Commission (CPSC) subsequently
accepted the method as a valid substitute for the GPMT and BT. The
Organization for Economic Co-operation and Development (OECD)
subsequently adopted the LLNA as OECD Test Guideline 429 in 2002. Using
the LLNA instead of guinea pig tests reduces and refines (less pain and
distress) animal use for ACD safety testing.
In 2007, the CPSC nominated several new versions and applications
of the LLNA to ICCVAM for evaluation of their scientific validity
(https://iccvam.niehs.nih.gov/methods/immunotox/llnadocs/CPSC_LLNA_nom.pdf). The nomination requested that ICCVAM assess (1) the
validation status of the LLNA limit dose procedure (i.e., the reduced
LLNA); (2) the 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; 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 (1) the appropriateness and relative priority of the CPSC-
nominated LLNA activities, (2) the nomination of scientists to serve on
an international independent scientific peer review panel, and (3) 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. ICCVAM assigned these activities a high priority after
considering comments from the public and endorsement from the
Scientific Advisory Committee on Alternative Toxicological Methods
(SACATM). NICEATM and ICCVAM compiled comprehensive draft background
review documents (BRDs), released them for public comment in January
2008 (73 FR 1360), and convened a public meeting of the panel on March
4-6, 2008 to peer review the draft documents. The panel evaluated the
information in the BRDs as to whether it supported draft ICCVAM test
method recommendations for test method uses and limitations, updated
standardized test method protocols, and proposed future studies. 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, the panel's report, and all public comments
were made available to SACATM for comment at its meeting on June 18-19,
2008 (73 FR 25754).
After considering the conclusions and recommendations of the panel,
comments from SACATM, and public comments, ICCVAM forwarded final
recommendations for the updated LLNA test method protocol, the reduced
LLNA, and LLNA performance standards to Federal agencies in September
2009 (74 FR 50212). ICCVAM concluded that the updated LLNA test method
protocol will further reduce animal use by 20% compared to the original
version of the LLNA and also provide for more consistent and reliable
results. The reduced LLNA will reduce animal use by 40% for each test
compared to the traditional, multi-dose LLNA. ICCVAM also recommended
LLNA test method performance standards that can be used to efficiently
evaluate the validity of modified versions of the LLNA that are
mechanistically and functionally similar to the traditional LLNA.
Federal agencies subsequently responded with their support and
concurrence with the ICCVAM recommendations. Agency responses are
available on the NICEATM-ICCVAM Web site.
NICEATM subsequently obtained additional data and/or information
and revised the draft documents for both the traditional and
nonradioactive LLNA methods. ICCVAM released the revised draft
documents to the public for comment and announced a second meeting of
the panel (74 FR 8974). The panel reconvened in public session on April
28-29, 2009 to review the ICCVAM-revised draft documents and
[[Page 37444]]
finalize its conclusions and recommendations on the current validation
status of the nonradioactive test methods and the expanded uses of the
LLNA for pesticide formulations and other products. The panel's report
was made available for public comment in June 2009 (74 FR 26242). The
revised draft ICCVAM BRDs, revised draft ICCVAM test method
recommendations, the panel's report, and all public comments were made
available to SACATM for comment on June 25-26, 2009 (74 FR 19562).
After considering the conclusions and recommendations of the panel,
comments from SACATM, and public comments, along with the
recommendations of an OECD Expert Consultation on the LLNA convened in
October and December 2009, ICCVAM finalized and forwarded test method
recommendations to Federal agencies for their 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 website as they are
received.
The ICCVAM TMERs, The LLNA: BrdU-ELISA, A Nonradioactive
Alternative Test Method to Assess the Allergic Contact Dermatitis
Potential of Chemicals and Products (NIH Publication 10-7552), and The
LLNA: DA, A Nonradioactive Alternative Test Method to Assess the
Allergic Contact Dermatitis Potential of Chemicals and Products (NIH
Publication 10-7551), describe ICCVAM's recommendations for using the
LLNA: BrdU-ELISA and LLNA: DA for regulatory hazard identification
purposes. The reports also provide ICCVAM-recommended LLNA: BrdU-ELISA
and LLNA: DA test method protocols, the final BRDs, and the peer review
reports of the panel. The ICCVAM-recommended LLNA: BrdU-ELISA test
method protocol is based on the protocol developed by Takeyoshi et al.
(2001). The ICCVAM-recommended LLNA: DA test method protocol is based
on the protocol developed by Idehara et al. (2008). Both test method
protocols incorporate all relevant aspects of the recently updated
ICCVAM-recommended traditional LLNA test method protocol (ICCVAM,
2009). The protocols also include reduced LLNA: BrdU-ELISA and LLNA: DA
procedures that should always be considered and used where determined
appropriate in order to further reduce animal use.
The ICCVAM Test Method Evaluation Report, Using the Murine Local
Lymph Node Assay for Testing Pesticide Formulations, Metals, Substances
in Aqueous Solutions, and Other Products (NIH Publication 10-7512)
provides ICCVAM's updated evaluation and recommendations for use of the
LLNA to evaluate the ACD hazard potential of pesticide formulations,
metals, substances in aqueous solutions, and other products. The
evaluation considered new data that became available subsequent to the
original ICCVAM LLNA evaluation in 1999. The report also includes the
peer review reports of the panel.
ICCVAM's evaluation of the LLNA for skin sensitization potency
categorization is currently nearing completion, and final ICCVAM
recommendations will be forwarded to Federal agencies later this year.
Background Information on ICCVAM, NICEATM, and SACATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that require, 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 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 (42 U.S.C 285l-3). 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.
NICEATM and ICCVAM welcome the public nomination of new, revised, and
alternative test methods for both validation studies as well as
technical evaluations. Additional information about ICCVAM and NICEATM
can be found on the NICEATM-ICCVAM Web site (https://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 https://ntp.niehs.nih.gov/go/167.
References
ICCVAM. 2010. ICCVAM Test Method Evaluation Report on The LLNA:
BrdU-ELISA, A Nonradioactive Alternative Test Method to Assess the
Allergic Contact Dermatitis Potential of Chemicals and Products. NIH
Publication Number 10-7552. Research Triangle Park, NC: National
Institute of Environmental Health Sciences.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report on The LLNA: DA,
A Nonradioactive Alternative Test Method to Assess the Allergic Contact
Dermatitis Potential of Chemicals and Products. NIH Publication Number
10-7551. Research Triangle Park, NC: National Institute of
Environmental Health Sciences.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report on Using the
Murine Local Lymph Node Assay for Testing Pesticide Formulations,
Metals, Substances in Aqueous Solutions, and Other Products. NIH
Publication Number 10-7512. Research Triangle Park, NC: National
Institute of Environmental Health Sciences.
ICCVAM. 2009. Recommended Performance Standards: Murine Local Lymph
Node Assay. NIH Publication Number 09-7357. Research Triangle Park, NC:
National Institute of Environmental Health Sciences. Available at:
https://iccvam.niehs.nih.gov/methods/immunotox/llna_PerfStds.htm.
ICCVAM. 2009. 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 Number 09-6439. Research
Triangle Park, NC: National Institute of Environmental Health Sciences.
Available at: https://iccvam.niehs.nih.gov/methods/immunotox/LLNA-LD/TMER.htm.
ICCVAM. 1999. The Murine Local Lymph Node Assay: A Test Method for
Assessing the Allergic Contact Dermatitis Potential of Chemicals/
Compounds. The Results of an Independent Peer Review Evaluation
Coordinated by ICCVAM and NICEATM. NIH Publication Number 99-4494.
Research Triangle Park, NC: National Institute of Environmental Health
Sciences. Available at: https://iccvam.niehs.nih.gov/methods/immunotox/llna.htm.
Idehara K, Yamagishi G, Yamashita K, Ito M. 2008. Characterization
and evaluation of a modified local lymph node assay using ATP content
as a non-radio isotopic endpoint. Journal of Pharmacological and
Toxicological Methods 58(1): 1-10.
Takeyoshi M, Yamasaki K, Yakabe Y, Takatsuki M, Kimber I. 2001.
Development of non-radio isotopic endpoint of murine local lymph node
[[Page 37445]]
assay based on 5-bromo-2'-deoxyuridine (BrdU) incorporation. Toxicology
Letters 119(3): 203-208.
Dated: June 16, 2010.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2010-15777 Filed 6-28-10; 8:45 am]
BILLING CODE 4140-01-P
