Recommendations on In Vitro Ocular Safety Testing Methods and Strategies and Routine Use of Topical Anesthetics, Systemic Analgesics, and Humane Endpoints for Ocular Safety Testing, 20672-20673 [2011-8938]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Recommendations on In Vitro Ocular
Safety Testing Methods and Strategies
and Routine Use of Topical
Anesthetics, Systemic Analgesics, and
Humane Endpoints for Ocular Safety
Testing
National Institute of
Environmental Health Sciences
(NIEHS), National Institutes of Health
(NIH).
ACTION: Notice of availability.
AGENCY:
U.S. Federal agency responses
to ICCVAM test method
recommendations on alternative testing
methods and strategies proposed to
further reduce and refine the use of
animals for assessing the ocular hazard
potential of chemicals and products are
now available. ICCVAM recommended a
pain management procedure that should
always be used to avoid pain and
distress when it is determined necessary
to conduct the rabbit eye test for
regulatory safety purposes. ICCVAM
also recommended the Cytosensor
Microphysiometer (CM) test method as
a screening test (1) to identify some
types of substances that will not cause
sufficient injury to require eye hazard
labeling and (2) to identify some types
of substances that may cause permanent
or severe eye injuries. ICCVAM
previously forwarded recommendations
to Federal agencies and made these
recommendations available to the
public (75 FR 57027). 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/
mstockstill on DSKH9S0YB1PROD with NOTICES
SUMMARY:
VerDate Mar<15>2010
18:37 Apr 12, 2011
Jkt 223001
48,000
ocutox/Transmit-2010.htm. The
ICCVAM recommendations are
provided in ICCVAM test method
evaluation reports that are available on
the NICEATM–ICCVAM Web site at
https://iccvam.niehs.nih.gov/methods/
ocutox/OcuAnest-TMER.htm, https://
iccvam.niehs.nih.gov/methods/ocutox/
MildMod-TMER.htm, https://
iccvam.niehs.nih.gov/methods/ocutox/
AMCP–TMER.htm, and https://
iccvam.niehs.nih.gov/methods/ocutox/
LVET.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)
niceatm@niehs.nih.gov. Courier address:
NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
Background
The U.S. Environmental Protection
Agency (EPA) requested that ICCVAM
(1) evaluate the current validation status
of the bovine corneal opacity and
permeability (BCOP), hen’s egg test–
chorioallantoic membrane (HET–CAM),
isolated chicken eye (ICE), and isolated
rabbit eye (IRE) test methods; (2)
identify in vivo ocular toxicity reference
data to support the validation of in vitro
test methods; (3) explore ways of
alleviating pain and distress from
current in vivo ocular safety testing; and
(4) review the state of the science and
the availability of in vitro test methods
for assessing mild or moderate ocular
irritants. The highest priority activity,
an evaluation of the BCOP, HET–CAM,
ICE, and IRE test methods for their
usefulness and limitations for
identifying potential ocular corrosives
and severe irritants, was completed in
2006 (NIH Publication No. 07–4517).
Based on this evaluation, U.S. Federal
agencies subsequently accepted the
BCOP and ICE test methods for certain
regulatory testing purposes without the
need for animal testing. The
Organisation for Economic Co-operation
and Development (OECD) subsequently
PO 00000
Frm 00050
Fmt 4703
Sfmt 4703
Number of
responses per
respondent
1
Average
burden hours
per response
(in hrs.)
Total burden
hours
12/60
9,600
adopted the BCOP and ICE test methods
in 2009 as international OECD Test
Guidelines 437 and 438, respectively
(OECD 2009a, OECD 2009b). The
International Organization for
Standardization (ISO) adopted the
BCOP and ICE test methods as ISO
Standard 10993–10 in 2010 (ISO 2010).
ICCVAM recently completed
additional test method evaluations
relevant to the original EPA nomination
and a subsequent EPA request that
ICCVAM evaluate a proposed in vitro
testing strategy for identifying the ocular
hazard potential of antimicrobial
cleaning products. Information is
provided about ICCVAM’s evaluation
and the committee’s recommendations
for the alternative testing methods and
strategies proposed to further reduce
and refine the use of animals for
assessing the ocular hazard potential of
chemicals and products in four
ICCVAM Test Method Evaluation
Reports: (1) Recommendations for
Routine Use of Topical Anesthetics,
Systemic Analgesics, and Humane
Endpoints to Avoid or Minimize Pain
and Distress in Ocular Safety Testing
(NIH Publication No. 10–7514), (2)
Current Validation Status of In Vitro
Test Methods Proposed for Identifying
Eye Injury Hazard Potential of
Chemicals and Products (NIH
Publication No. 10–7553), (3) Current
Validation Status of a Proposed In Vitro
Testing Strategy for U.S. Environmental
Protection Agency Ocular Hazard
Classification and Labeling of
Antimicrobial Cleaning Products (NIH
Publication No. 10–7513), and (4)
Recommendation to Discontinue Use of
the Low Volume Eye Test for Ocular
Safety Testing (NIH Publication No.
10–7515).
Agency Responses to ICCVAM
Recommendations
In September 2010, ICCVAM
forwarded final test method
recommendations for ocular safety
testing methods and strategies to U.S.
Federal agencies for consideration, in
accordance with the ICCVAM
Authorization Act of 2000 (42 U.S.C.
E:\FR\FM\13APN1.SGM
13APN1
Federal Register / Vol. 76, No. 71 / Wednesday, April 13, 2011 / Notices
mstockstill on DSKH9S0YB1PROD with NOTICES
285l–3) (75 FR 57027). 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 should 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.
ICCVAM agencies concurred with the
test method recommendations for the in
vitro ocular safety testing methods and
strategies and support the routine use of
topical anesthetics, systemic analgesics,
and humane endpoints for ocular safety
testing. Several agencies also indicated
that they would communicate the
ICCVAM recommendations to
stakeholders and encourage their
appropriate use. Agency responses are
available at https://iccvam.niehs.nih.gov/
methods/ocutox/Transmit-2010.htm.
Background Information on ICCVAM
and NICEATM
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 and that
reduce, refine (decrease or eliminate
pain and distress), or replace animal
use. 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
VerDate Mar<15>2010
18:37 Apr 12, 2011
Jkt 223001
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).
References
ICCVAM. 2006. ICCVAM Test Method
Evaluation Report: In Vitro Ocular
Toxicity Test Methods for Identifying
Severe Irritants and Corrosives. NIH
Publication No. 07– 4517. Research
Triangle Park, NC: NIEHS. Available:
https://iccvam.niehs.nih.gov/methods/
ocutox/ivocutox/ocu_tmer.htm.
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report: Recommendations for
Routine Use of Topical Anesthetics,
Systemic Analgesics, and Humane
Endpoints to Avoid or Minimize Pain
and Distress in Ocular Safety Testing.
NIH Publication No. 10–7514. Research
Triangle Park, NC: NIEHS. Available:
https://iccvam.niehs.nih.gov/methods/
ocutox/OcuAnest-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report: Current Validation
Status of In Vitro Test Methods Proposed
for Identifying Eye Injury Hazard
Potential of Chemicals and Products.
NIH Publication No. 10–7553. Research
Triangle Park, NC: NIEHS. Available:
https://iccvam.niehs.nih.gov/methods/
ocutox/MildMod-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report: Current Validation
Status of a Proposed In Vitro Testing
Strategy for U.S. Environmental
Protection Agency Ocular Hazard
Classification and Labeling of
Antimicrobial Cleaning Products. NIH
Publication No. 10– 7513. Research
Triangle Park, NC: NIEHS. Available:
https://iccvam.niehs.nih.gov/methods/
ocutox/AMCP-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method
Evaluation Report: Recommendation to
Discontinue Use of The Low Volume Eye
Test for Ocular Safety Testing. NIH
Publication No. 10–7515. Research
Triangle Park, NC: NIEHS. Available:
https://iccvam.niehs.nih.gov/methods/
ocutox/LVET.htm.
ISO. 2010. Biological evaluation of medical
devices—10993 Part 10: Tests for
irritation and skin sensitization.
Available for purchase at: https://
www.iso.org/iso/home.htm.
OECD. 2009a. Test Guideline 437. Bovine
Corneal Opacity and Permeability Test
Method for Identifying Ocular Corrosives
and Severe Irritants, adopted September
2009. In: OECD Guidelines for Testing of
Chemicals. Paris: OECD. Available:
https://www.oecd-ilibrary.org/
environment/test-no-437-bovine-cornealopacity-and-permeability-test-methodfor-identifying-ocular-corrosives-andsevere-irritants_9789264076303-en.
OECD. 2009b. Test Guideline 438. Isolated
Chicken Eye Test Method for Identifying
Ocular Corrosives and Severe Irritants,
adopted September 2009. In: OECD
Guidelines for Testing of Chemicals.
Paris: OECD. Available: https://
PO 00000
Frm 00051
Fmt 4703
Sfmt 4703
20673
www.oecd-ilibrary.org/environment/testno-438-isolated-chicken-eye-testmethod-for-identifying-ocular-corrosivesand-severe-irritants_9789264076310-en.
Dated: April 1, 2011.
John R. Bucher,
Associate Director, National Toxicology
Program.
[FR Doc. 2011–8938 Filed 4–12–11; 8:45 am]
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Centers for Medicare &
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must be mailed to the Centers for
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Savoy, Contracting Officer, 7500
Security Boulevard, Mailstop C2–01–10,
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Candice.Savoy@cms.hhs.gov.
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Candice Savoy, (410) 786–7494.
SUPPLEMENTARY INFORMATION: The
Centers for Medicare & Medicaid
Services (CMS), an operating division
within the Department of Health and
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Federally Funded Research and
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E:\FR\FM\13APN1.SGM
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[Federal Register Volume 76, Number 71 (Wednesday, April 13, 2011)]
[Notices]
[Pages 20672-20673]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-8938]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Recommendations on In Vitro Ocular Safety Testing Methods and
Strategies and Routine Use of Topical Anesthetics, Systemic Analgesics,
and Humane Endpoints for Ocular Safety Testing
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH).
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: U.S. Federal agency responses to ICCVAM test method
recommendations on alternative testing methods and strategies proposed
to further reduce and refine the use of animals for assessing the
ocular hazard potential of chemicals and products are now available.
ICCVAM recommended a pain management procedure that should always be
used to avoid pain and distress when it is determined necessary to
conduct the rabbit eye test for regulatory safety purposes. ICCVAM also
recommended the Cytosensor Microphysiometer (CM) test method as a
screening test (1) to identify some types of substances that will not
cause sufficient injury to require eye hazard labeling and (2) to
identify some types of substances that may cause permanent or severe
eye injuries. ICCVAM previously forwarded recommendations to Federal
agencies and made these recommendations available to the public (75 FR
57027). 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/ocutox/Transmit-2010.htm. The
ICCVAM recommendations are provided in ICCVAM test method evaluation
reports that are available on the NICEATM-ICCVAM Web site at https://iccvam.niehs.nih.gov/methods/ocutox/OcuAnest-TMER.htm, https://iccvam.niehs.nih.gov/methods/ocutox/MildMod-TMER.htm, https://iccvam.niehs.nih.gov/methods/ocutox/AMCP-TMER.htm, and https://iccvam.niehs.nih.gov/methods/ocutox/LVET.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)
niceatm@niehs.nih.gov. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
Background
The U.S. Environmental Protection Agency (EPA) requested that
ICCVAM (1) evaluate the current validation status of the bovine corneal
opacity and permeability (BCOP), hen's egg test-chorioallantoic
membrane (HET-CAM), isolated chicken eye (ICE), and isolated rabbit eye
(IRE) test methods; (2) identify in vivo ocular toxicity reference data
to support the validation of in vitro test methods; (3) explore ways of
alleviating pain and distress from current in vivo ocular safety
testing; and (4) review the state of the science and the availability
of in vitro test methods for assessing mild or moderate ocular
irritants. The highest priority activity, an evaluation of the BCOP,
HET-CAM, ICE, and IRE test methods for their usefulness and limitations
for identifying potential ocular corrosives and severe irritants, was
completed in 2006 (NIH Publication No. 07-4517). Based on this
evaluation, U.S. Federal agencies subsequently accepted the BCOP and
ICE test methods for certain regulatory testing purposes without the
need for animal testing. The Organisation for Economic Co-operation and
Development (OECD) subsequently adopted the BCOP and ICE test methods
in 2009 as international OECD Test Guidelines 437 and 438, respectively
(OECD 2009a, OECD 2009b). The International Organization for
Standardization (ISO) adopted the BCOP and ICE test methods as ISO
Standard 10993-10 in 2010 (ISO 2010).
ICCVAM recently completed additional test method evaluations
relevant to the original EPA nomination and a subsequent EPA request
that ICCVAM evaluate a proposed in vitro testing strategy for
identifying the ocular hazard potential of antimicrobial cleaning
products. Information is provided about ICCVAM's evaluation and the
committee's recommendations for the alternative testing methods and
strategies proposed to further reduce and refine the use of animals for
assessing the ocular hazard potential of chemicals and products in four
ICCVAM Test Method Evaluation Reports: (1) Recommendations for Routine
Use of Topical Anesthetics, Systemic Analgesics, and Humane Endpoints
to Avoid or Minimize Pain and Distress in Ocular Safety Testing (NIH
Publication No. 10-7514), (2) Current Validation Status of In Vitro
Test Methods Proposed for Identifying Eye Injury Hazard Potential of
Chemicals and Products (NIH Publication No. 10-7553), (3) Current
Validation Status of a Proposed In Vitro Testing Strategy for U.S.
Environmental Protection Agency Ocular Hazard Classification and
Labeling of Antimicrobial Cleaning Products (NIH Publication No. 10-
7513), and (4) Recommendation to Discontinue Use of the Low Volume Eye
Test for Ocular Safety Testing (NIH Publication No. 10-7515).
Agency Responses to ICCVAM Recommendations
In September 2010, ICCVAM forwarded final test method
recommendations for ocular safety testing methods and strategies to
U.S. Federal agencies for consideration, in accordance with the ICCVAM
Authorization Act of 2000 (42 U.S.C.
[[Page 20673]]
285l-3) (75 FR 57027). 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 should 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.
ICCVAM agencies concurred with the test method recommendations for
the in vitro ocular safety testing methods and strategies and support
the routine use of topical anesthetics, systemic analgesics, and humane
endpoints for ocular safety testing. Several agencies also indicated
that they would communicate the ICCVAM recommendations to stakeholders
and encourage their appropriate use. Agency responses are available at
https://iccvam.niehs.nih.gov/methods/ocutox/Transmit-2010.htm.
Background Information on ICCVAM and NICEATM
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 and that reduce, refine (decrease or
eliminate pain and distress), or replace animal use. 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).
References
ICCVAM. 2006. ICCVAM Test Method Evaluation Report: In Vitro Ocular
Toxicity Test Methods for Identifying Severe Irritants and
Corrosives. NIH Publication No. 07- 4517. Research Triangle Park,
NC: NIEHS. Available: https://iccvam.niehs.nih.gov/methods/ocutox/ivocutox/ocu_tmer.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Recommendations
for Routine Use of Topical Anesthetics, Systemic Analgesics, and
Humane Endpoints to Avoid or Minimize Pain and Distress in Ocular
Safety Testing. NIH Publication No. 10-7514. Research Triangle Park,
NC: NIEHS. Available: https://iccvam.niehs.nih.gov/methods/ocutox/OcuAnest-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Current
Validation Status of In Vitro Test Methods Proposed for Identifying
Eye Injury Hazard Potential of Chemicals and Products. NIH
Publication No. 10-7553. Research Triangle Park, NC: NIEHS.
Available: https://iccvam.niehs.nih.gov/methods/ocutox/MildMod-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Current
Validation Status of a Proposed In Vitro Testing Strategy for U.S.
Environmental Protection Agency Ocular Hazard Classification and
Labeling of Antimicrobial Cleaning Products. NIH Publication No. 10-
7513. Research Triangle Park, NC: NIEHS. Available: https://iccvam.niehs.nih.gov/methods/ocutox/AMCP-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Recommendation
to Discontinue Use of The Low Volume Eye Test for Ocular Safety
Testing. NIH Publication No. 10-7515. Research Triangle Park, NC:
NIEHS. Available: https://iccvam.niehs.nih.gov/methods/ocutox/LVET.htm.
ISO. 2010. Biological evaluation of medical devices--10993 Part 10:
Tests for irritation and skin sensitization. Available for purchase
at: https://www.iso.org/iso/home.htm.
OECD. 2009a. Test Guideline 437. Bovine Corneal Opacity and
Permeability Test Method for Identifying Ocular Corrosives and
Severe Irritants, adopted September 2009. In: OECD Guidelines for
Testing of Chemicals. Paris: OECD. Available: https://www.oecd-ilibrary.org/environment/test-no-437-bovine-corneal-opacity-and-permeability-test-method-for-identifying-ocular-corrosives-and-severe-irritants_9789264076303-en.
OECD. 2009b. Test Guideline 438. Isolated Chicken Eye Test Method
for Identifying Ocular Corrosives and Severe Irritants, adopted
September 2009. In: OECD Guidelines for Testing of Chemicals. Paris:
OECD. Available: https://www.oecd-ilibrary.org/environment/test-no-438-isolated-chicken-eye-test-method-for-identifying-ocular-corrosives-and-severe-irritants_9789264076310-en.
Dated: April 1, 2011.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2011-8938 Filed 4-12-11; 8:45 am]
BILLING CODE 4140-01-P