[Federal Register Volume 76, Number 71 (Wednesday, April 13, 2011)]
[Notices]
[Pages 20672-20673]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 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

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 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 http://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 http://iccvam.niehs.nih.gov/methods/ocutox/OcuAnest-TMER.htm, http://iccvam.niehs.nih.gov/methods/ocutox/MildMod-TMER.htm, http://iccvam.niehs.nih.gov/methods/ocutox/AMCP-TMER.htm, and http://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) 
[email protected]. 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 
http://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 (http://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: http://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: http://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: http://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: http://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: http://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: http://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: http://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: http://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