Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Recommendations on the Use of the Murine Local Lymph Node Assay for Potency Categorization of Chemicals Causing Allergic Contact Dermatitis: Availability of Federal Agency Responses, 11536-11538 [2012-4541]
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Interagency Coordinating Committee
on the Validation of Alternative
Methods (ICCVAM) Recommendations
on the Use of the Murine Local Lymph
Node Assay for Potency
Categorization of Chemicals Causing
Allergic Contact Dermatitis:
Availability of Federal Agency
Responses
Division of the National
Toxicology Program (DNTP), National
Institute of Environmental Health
Sciences (NIEHS), National Institutes of
Health (NIH).
ACTION: Availability of Agency
Responses.
AGENCY:
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1000, Washington, DC 20002. All
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
The NTP Interagency Center
for the Evaluation of Alternative
Toxicological Methods (NICEATM)
announces availability of U.S. Federal
agency responses to ICCVAM test
method recommendations on the use of
the murine local lymph node assay
(LLNA) for potency categorization of
chemicals causing allergic contact
dermatitis (ACD). ICCVAM forwarded
the recommendations to Federal
agencies and made these
recommendations available to the
public (76 FR 45254). In accordance
with the ICCVAM Authorization Act of
2000 (42 U.S.C. 285l–3), agencies have
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
https://iccvam.niehs.nih.gov/methods/
immunotox/LLNApotency.htm. The
ICCVAM recommendations are
provided in the ICCVAM test method
evaluation report (ICCVAM, 2011).
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, (email)
niceatm@niehs.nih.gov. Courier address:
NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
SUMMARY:
Background
The LLNA is accepted worldwide as
a valid alternative to traditionally
accepted guinea pig test methods for
assessing ACD hazard potential for most
testing applications. In January 2007,
the U.S. Consumer Product Safety
Commission (CPSC) requested that
NICEATM and ICCVAM evaluate the
LLNA for its usefulness for determining
skin sensitization potency categories.
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Federal Register / Vol. 77, No. 38 / Monday, February 27, 2012 / Notices
The CPSC, under the Federal Hazardous
Substances Act, requires hazard labeling
of products considered to be strong skin
sensitizers. Results from tests that could
be used to identify potential strong
human skin sensitizers would support
the CPSC and other agencies with an
interest in identifying strong skin
sensitizers. While guinea pig tests have
traditionally been used to categorize the
potency of skin sensitizers, the LLNA
uses fewer animals, requires less time to
perform, provides dose-response
information, and eliminates the pain
and distress produced by positive
reactions.
Accordingly, NICEATM and ICCVAM
evaluated the extent that the LLNA
could be used to correctly predict
‘‘strong’’ versus ‘‘other than strong’’
human skin sensitizers. NICEATM,
working in collaboration with the
ICCVAM Interagency Immunotoxicity
Working Group (IWG), prepared a draft
background review document (BRD) and
draft recommendations for use of the
LLNA for potency categorization of
chemicals that cause ACD in humans.
The draft BRD and draft ICCVAM
recommendations were reviewed in a
public meeting of an international
independent scientific peer review
panel in March 2008; the peer review
panel report was made available to the
public for comment in May 2008 (73 FR
29136). The Scientific Advisory
Committee on Alternative Toxicological
Methods (SACATM) discussed and
commented on the report, draft BRD,
and draft ICCVAM recommendations at
its June 2008 meeting (73 FR 25754).
ICCVAM considered the panel’s report,
comments from SACATM, and public
comments, and finalized its
recommendations.
The final ICCVAM recommendations
are provided in the ICCVAM Test
Method Evaluation Report: Usefulness
and Limitations of the Murine Local
Lymph Node Assay for Potency
Categorization of Chemicals Causing
Allergic Contact Dermatitis in Humans
(NIH Publication No. 11–7709, available
at https://iccvam.niehs.nih.gov/methods/
immunotox/LLNA-pot/TMER.htm). The
test method evaluation report also
includes an updated ICCVAMrecommended LLNA protocol and
recommended future studies that may
further characterize the usefulness and
limitations of the LLNA for potency
determinations. The final BRD,
including additional analyses performed
by NICEATM as recommended by the
peer review panel, is included as an
appendix to the test method evaluation
report. ICCVAM recommended that
positive results from ACD safety testing
using the murine LLNA could be used
VerDate Mar<15>2010
18:10 Feb 24, 2012
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to categorize some chemicals and
products as strong skin sensitizers.
However, since the current LLNA
decision criterion only identified 52%
of the strong human skin sensitizers,
ICCVAM recommended that this
criterion should not be used as the basis
for determining that a substance is not
a strong skin sensitizer. Therefore, the
potency criterion should only be used in
a screening approach, where chemicals
that meet the criterion could be
categorized as strong skin sensitizers,
but chemicals that do not meet the
criterion would require additional
testing or information to determine that
they are not strong skin sensitizers. In
accordance with the Public Health
Service Policy on Humane Care and Use
of Laboratory Animals and Animal
Welfare Act regulations, the LLNA
should be routinely considered when
planning animal studies to evaluate
whether chemicals and products are
strong sensitizers in order to minimize
animal use and to avoid unrelieved pain
and distress, and should be used when
determined appropriate.
Agency Responses to ICCVAM
Recommendations
In June 2011, ICCVAM forwarded
final test method recommendations on
using the LLNA for potency
categorization of chemicals to U.S.
Federal agencies for consideration (76
FR 45254), in accordance with the
ICCVAM Authorization Act of 2000 (42
U.S.C. 285l–3). 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.
Complete agency responses are available
at https://iccvam.niehs.nih.gov/methods/
immunotox/LLNApotency.htm.
Background Information on NICEATM,
ICCVAM, and SACATM
ICCVAM is an interagency committee
composed of representatives from 15
Federal regulatory and research agencies
that require, use, generate, or
disseminate toxicological and safety
testing information. ICCVAM conducts
technical evaluations of new, revised,
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11537
and alternative safety testing methods
with regulatory applicability and
promotes the scientific validation and
regulatory acceptance of toxicological
and safety testing methods that more
accurately assess the safety and hazards
of chemicals and products while
reducing animal use, refining animal
use by enhancing animal welfare and
lessening or avoiding unrelieved pain
and distress, or replacing animals used
for testing. The ICCVAM Authorization
Act of 2000 (42 U.S.C. 285l–3)
established ICCVAM as a permanent
interagency committee of the NIEHS
under NICEATM. NICEATM
administers ICCVAM, provides
scientific and operational support for
ICCVAM-related activities, and
conducts independent validation
studies to assess the usefulness and
limitations of new, revised, and
alternative test methods and strategies.
NICEATM and ICCVAM work
collaboratively to evaluate new and
improved test methods and strategies
applicable to the needs of U.S. Federal
agencies. NICEATM and ICCVAM
welcome the public nomination of new,
revised, and alternative test methods
and strategies for validation studies and
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 in response
to the ICCVAM Authorization Act
[Section 285l–3(d)] and is composed of
scientists from the public and private
sectors (67 FR 11358). SACATM advises
ICCVAM, NICEATM, and the Director of
the NIEHS and NTP regarding
statutorily mandated duties of ICCVAM
and activities of NICEATM. SACATM
provides advice on priorities and
activities related to the development,
validation, scientific review, regulatory
acceptance, implementation, and
national and international
harmonization of new, revised, and
alternative toxicological test methods.
Additional information about SACATM,
including the charter, roster, and
records of past meetings, can be found
at https://ntp.niehs.nih.gov/go/167.
Reference
ICCVAM. 2011. ICCVAM Test Method
Evaluation Report: Usefulness and
Limitations of the Murine Local Lymph
Node Assay for Potency Categorization of
Chemicals Causing Allergic Contact
Dermatitis in Humans. NIH Publication No.
11–7709. Research Triangle Park, NC:
National Institute of Environmental Health
Sciences. Available: https://
iccvam.niehs.nih.gov/methods/
immunotox/LLNA-pot/TMER.htm.
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11538
Federal Register / Vol. 77, No. 38 / Monday, February 27, 2012 / Notices
Dated: February 15, 2012.
John R. Bucher,
Associate Director, National Toxicology
Program.
[FR Doc. 2012–4541 Filed 2–24–12; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Office of the Secretary
Findings of Research Misconduct
Office of the Secretary, HHS.
Notice.
AGENCY:
ACTION:
Notice is hereby given that
the Office of Research Integrity (ORI)
has taken final action in the following
case:
Michael W. Miller, Ph.D., State
University of New York, Upstate
Medical University: Based on the report
of an investigation conducted by the
State University of New York, Upstate
Medical University (SUNY UMU) and
additional analysis conducted by ORI in
its oversight review, ORI found that Dr.
Michael W. Miller, former Professor and
Chair, Department of Neuroscience and
Physiology, SUNY UMU, engaged in
research misconduct in research
supported by National Institute of
Alcohol Abuse and Alcoholism
(NIAAA), National Institutes of Health
(NIH), grants R01 AA07568–18A1, R01
AA06916, and P50 AA017823–01.
ORI finds that the Respondent
engaged in research misconduct by
falsifying and/or fabricating data that
were included in grant applications R01
AA07568–18, R01 AA07568–18A1, R01
AA006916–25, and P50 AA017823–01
and in the following:
• Miller, M.W., Hu, H. ‘‘Lability of
neuronal lineage decisions is revealed
by acute exposures to ethanol.’’ Dev.
Neurosci. 31(1–2):50–7, 2009 (‘‘Dev.
Neurosci. 2009’’)
• Bruns, M.B., Miller, M.W.
‘‘Functional nerve growth factor and
trkA autocrine/paracrine circuits in
adult rat cortex are revealed by episodic
ethanol exposure and withdrawal.’’ J.
Neurochem. 100(5):1115–68, 2007 (‘‘J.
Neurochem. 2007’’)
• A prepared manuscript submitted
to PNAS for publication.
As a result of its investigation, SUNY
UMU recommended that Dev. Neurosci.
2009 and J. Neurochem. 2007 be
retracted. Both publications have now
been retracted:
• Dev. Neurosci. 2009 was retracted
online on January 19, 2012, at: https://
content.karger.com/ProdukteDB/
produkte.asp?Aktion=
ShowPDF&ArtikelNr=
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SUMMARY:
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323471&Ausgabe=0&ProduktNr=
224107&filename=323471.pdf.
• J. Neurochem. 2007 was retracted
online on January 23, 2012, at: https://
onlinelibrary.wiley.com/doi/10.1111/
j.1471-4159.2012.07662.x/full.
Specifically, ORI finds that the
Respondent:
• Falsified Figure 5 in NIH grant
application R01 AA07568–18A1 by
altering the bar graphs to make the
experimental results appear valid and
consistent with his hypothesis that
ethanol exposure in-utero alters the
transition of cells from Pax 6 expression
to Tbr2 expression, which is critical to
normal brain development. Specifically:
a. In the VZ/SZ panel (upper row,
right), Dr. Miller decreased the values
by 50% for the bar graphs representing
control and treated mice for ‘‘Tbr2,’’
‘‘both,’’ and ‘‘both/Ki-67,’’ to falsely
report an equivalent frequency of Tbr2
expressing cells in the right and left
panels; this result was required for the
experiment to appear valid;
b. In the MGE panel (lower row,
right), Dr. Miller altered the bar graphs
representing control and treated mice
for ‘‘Ki-67,’’ ‘‘Pax6,’’ and ‘‘both’’ to
falsely report that ethanol increased the
frequency of K–67+ cells and to report
an equivalent frequency of Pax
expressing cells in the right and left
panels.
• Fabricated bar graphs in
Supplemental Figure 2 in a manuscript
submitted to PNAS and text in the
manuscript also appearing in the grant
application AA00616–25 to support the
hypothesis that ethanol exposure during
postnatal weeks 1 and 2 causes specific
neuronal cell death in layers II/III and
V of the cortex. Specifically, Dr. Miller:
a. Fabricated bar graphs in
Supplemental Figure 2 and related text
in the PNAS manuscript to show that in
select layers of the cortex, ethanol
induced neuronal death occurred in
post-natal day 10 (P10) mice;
b. Included fabricated text in the
PNAS manuscript and the grant
application citing results of experiments
using 15–25-day-old mice treated with
ethanol during the second postnatal
week, when these mice were never
generated.
• Falsified Figure 6 in a manuscript
submitted to PNAS by altering data
points for the labeling index of caspase3
and TUNEL in cortex layers II/III and V
after exposure to ethanol in postnatal
day 7 (P7) mice, such that the two
assays confirmed each other. The same
data were also included as Figure 4 in
NIH grant application R01 AA06916 and
as Figure 7 in a poster presentation at
the 2009 Research Society on
Alcoholism.
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• Falsified the figure legends and/or
text in a published paper and multiple
grant applications to support the
primary hypothesis of the published
paper that gestational alcohol exposure
had an effect on brain development by
affecting the way neurons differentiate
and migrate into the cortex, rather than
by changes to cell growth or death.
Specifically, Dr. Miller falsely reported
the number of animals (n) that were
used in figure legends and/or text in the
following:
Æ Figures 2 and 5, Dev. Neurosci.
2009, also included as Figures 3 and 4,
respectively, in R01 AA07568–18;
Æ Figure 4 and Table 2 in P50
AA017823–01.
• Falsified Figures 4 and 6 in J.
Neurochem. 2007 by altering bar graphs
to increase the significance of the effect
of ethanol exposure and/or withdrawal
on NGF or trkA protein expression,
thereby conforming with the paper’s
hypothesis that ethanol exposure and
withdrawal affect the normal NGF/trkA
circuits in cortical layer V. Specifically,
Dr. Miller:
a. Increased the value of the ethanol
treated NGF expression in Figure 4 and
decreased the value of withdrawal NFG
to alter the difference between the two
from approximately 2.2% to 11.6%,
thereby falsely reporting significance
where there was none;
b. In Figure 6:
(a) Increased the value of withdrawal
trkA data by approximately 70% to
falsely report significance with relation
to the ethanol treated value and increase
significance with relation to the control;
(b) Increased the value of the ethanol
treated phospho-trkA data by
approximately 100% to increase the
significance with relation to the control;
(c) Falsely reported the results for
Figure 6 as showing a nearly doubled
ratio of p-trkA to total trkA after ethanol
exposure when there was no increase at
all.
Dr. Miller has entered into a
Voluntary Exclusion Agreement
(Agreement). Dr. Miller neither admits
nor denies committing research
misconduct but accepts ORI has found
evidence of research misconduct as set
forth above.
Dr. Miller has voluntarily agreed:
(1) To exclude himself voluntarily
from any contracting or subcontracting
with any agency of the United States
Government and from eligibility or
involvement in nonprocurement
programs of the United States
Government referred to as ‘‘covered
transactions’’ pursuant to HHS’
Implementation (2 CFR part 376 et seq)
of OMB Guidelines to Agencies on
Governmentwide Debarment and
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Agencies
[Federal Register Volume 77, Number 38 (Monday, February 27, 2012)]
[Notices]
[Pages 11536-11538]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-4541]
=======================================================================
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Interagency Coordinating Committee on the Validation of
Alternative Methods (ICCVAM) Recommendations on the Use of the Murine
Local Lymph Node Assay for Potency Categorization of Chemicals Causing
Allergic Contact Dermatitis: Availability of Federal Agency Responses
AGENCY: Division of the National Toxicology Program (DNTP), National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health (NIH).
ACTION: Availability of Agency Responses.
-----------------------------------------------------------------------
SUMMARY: The NTP Interagency Center for the Evaluation of Alternative
Toxicological Methods (NICEATM) announces availability of U.S. Federal
agency responses to ICCVAM test method recommendations on the use of
the murine local lymph node assay (LLNA) for potency categorization of
chemicals causing allergic contact dermatitis (ACD). ICCVAM forwarded
the recommendations to Federal agencies and made these recommendations
available to the public (76 FR 45254). In accordance with the ICCVAM
Authorization Act of 2000 (42 U.S.C. 285l-3), agencies have 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 https://iccvam.niehs.nih.gov/methods/immunotox/LLNApotency.htm. The ICCVAM
recommendations are provided in the ICCVAM test method evaluation
report (ICCVAM, 2011).
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, (email)
niceatm@niehs.nih.gov. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
Background
The LLNA is accepted worldwide as a valid alternative to
traditionally accepted guinea pig test methods for assessing ACD hazard
potential for most testing applications. In January 2007, the U.S.
Consumer Product Safety Commission (CPSC) requested that NICEATM and
ICCVAM evaluate the LLNA for its usefulness for determining skin
sensitization potency categories.
[[Page 11537]]
The CPSC, under the Federal Hazardous Substances Act, requires hazard
labeling of products considered to be strong skin sensitizers. Results
from tests that could be used to identify potential strong human skin
sensitizers would support the CPSC and other agencies with an interest
in identifying strong skin sensitizers. While guinea pig tests have
traditionally been used to categorize the potency of skin sensitizers,
the LLNA uses fewer animals, requires less time to perform, provides
dose-response information, and eliminates the pain and distress
produced by positive reactions.
Accordingly, NICEATM and ICCVAM evaluated the extent that the LLNA
could be used to correctly predict ``strong'' versus ``other than
strong'' human skin sensitizers. NICEATM, working in collaboration with
the ICCVAM Interagency Immunotoxicity Working Group (IWG), prepared a
draft background review document (BRD) and draft recommendations for
use of the LLNA for potency categorization of chemicals that cause ACD
in humans. The draft BRD and draft ICCVAM recommendations were reviewed
in a public meeting of an international independent scientific peer
review panel in March 2008; the peer review panel report was made
available to the public for comment in May 2008 (73 FR 29136). The
Scientific Advisory Committee on Alternative Toxicological Methods
(SACATM) discussed and commented on the report, draft BRD, and draft
ICCVAM recommendations at its June 2008 meeting (73 FR 25754). ICCVAM
considered the panel's report, comments from SACATM, and public
comments, and finalized its recommendations.
The final ICCVAM recommendations are provided in the ICCVAM Test
Method Evaluation Report: Usefulness and Limitations of the Murine
Local Lymph Node Assay for Potency Categorization of Chemicals Causing
Allergic Contact Dermatitis in Humans (NIH Publication No. 11-7709,
available at https://iccvam.niehs.nih.gov/methods/immunotox/LLNA-pot/TMER.htm). The test method evaluation report also includes an updated
ICCVAM-recommended LLNA protocol and recommended future studies that
may further characterize the usefulness and limitations of the LLNA for
potency determinations. The final BRD, including additional analyses
performed by NICEATM as recommended by the peer review panel, is
included as an appendix to the test method evaluation report. ICCVAM
recommended that positive results from ACD safety testing using the
murine LLNA could be used to categorize some chemicals and products as
strong skin sensitizers. However, since the current LLNA decision
criterion only identified 52% of the strong human skin sensitizers,
ICCVAM recommended that this criterion should not be used as the basis
for determining that a substance is not a strong skin sensitizer.
Therefore, the potency criterion should only be used in a screening
approach, where chemicals that meet the criterion could be categorized
as strong skin sensitizers, but chemicals that do not meet the
criterion would require additional testing or information to determine
that they are not strong skin sensitizers. In accordance with the
Public Health Service Policy on Humane Care and Use of Laboratory
Animals and Animal Welfare Act regulations, the LLNA should be
routinely considered when planning animal studies to evaluate whether
chemicals and products are strong sensitizers in order to minimize
animal use and to avoid unrelieved pain and distress, and should be
used when determined appropriate.
Agency Responses to ICCVAM Recommendations
In June 2011, ICCVAM forwarded final test method recommendations on
using the LLNA for potency categorization of chemicals to U.S. Federal
agencies for consideration (76 FR 45254), in accordance with the ICCVAM
Authorization Act of 2000 (42 U.S.C. 285l-3). 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. Complete agency responses are available at
https://iccvam.niehs.nih.gov/methods/immunotox/LLNApotency.htm.
Background Information on NICEATM, ICCVAM, and SACATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that require, use,
generate, or disseminate toxicological and safety testing information.
ICCVAM conducts technical evaluations of new, revised, and alternative
safety testing methods with regulatory applicability and promotes the
scientific validation and regulatory acceptance of toxicological and
safety testing methods that more accurately assess the safety and
hazards of chemicals and products while reducing animal use, refining
animal use by enhancing animal welfare and lessening or avoiding
unrelieved pain and distress, or replacing animals used for testing.
The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-3) established
ICCVAM as a permanent interagency committee of the NIEHS under NICEATM.
NICEATM administers ICCVAM, provides scientific and operational support
for ICCVAM-related activities, and conducts independent validation
studies to assess the usefulness and limitations of new, revised, and
alternative test methods and strategies. NICEATM and ICCVAM work
collaboratively to evaluate new and improved test methods and
strategies applicable to the needs of U.S. Federal agencies. NICEATM
and ICCVAM welcome the public nomination of new, revised, and
alternative test methods and strategies for validation studies and
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 in response to the ICCVAM Authorization Act
[Section 285l-3(d)] and is composed of scientists from the public and
private sectors (67 FR 11358). SACATM advises ICCVAM, NICEATM, and the
Director of the NIEHS and NTP regarding statutorily mandated duties of
ICCVAM and activities of NICEATM. SACATM provides advice on priorities
and activities related to the development, validation, scientific
review, regulatory acceptance, implementation, and national and
international harmonization of new, revised, and alternative
toxicological test methods. Additional information about SACATM,
including the charter, roster, and records of past meetings, can be
found at https://ntp.niehs.nih.gov/go/167.
Reference
ICCVAM. 2011. ICCVAM Test Method Evaluation Report: Usefulness and
Limitations of the Murine Local Lymph Node Assay for Potency
Categorization of Chemicals Causing Allergic Contact Dermatitis in
Humans. NIH Publication No. 11-7709. Research Triangle Park, NC:
National Institute of Environmental Health Sciences. Available:
https://iccvam.niehs.nih.gov/methods/immunotox/LLNA-pot/TMER.htm.
[[Page 11538]]
Dated: February 15, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-4541 Filed 2-24-12; 8:45 am]
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