[Federal Register Volume 77, Number 135 (Friday, July 13, 2012)]
[Notices]
[Pages 41406-41408]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-17118]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Evaluation of In Vitro Tests for Identifying Eye Injury Hazard 
Potential of Chemicals and Products: Request for Nominations for an 
Independent Expert Panel and Submission of Relevant Data

AGENCY: Division of the National Toxicology Program (DNTP), National 
Institute of Environmental Health Sciences (NIEHS), National Institutes 
of Health (NIH).

ACTION: Request for Data; Request for Nomination of Scientific Experts.

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[[Page 41407]]

SUMMARY: The NTP Interagency Center for the Evaluation of Alternative 
Toxicological Methods (NICEATM), in collaboration with the Interagency 
Coordinating Committee on the Validation of Alternative Methods 
(ICCVAM), is planning to convene an independent scientific peer review 
panel (Panel) to assess the validation status of in vitro tests and 
integrated non-animal testing strategies proposed for identifying eye 
injury hazard potential of chemicals and products. On behalf of ICCVAM, 
NICEATM requests nominations of scientific experts who can be 
considered for the Panel and submission of data from substances tested 
in in vitro tests for identifying eye injury hazard potential. Of 
particular interest are data generated in the short-time exposure (STE) 
(Takahashi et al., 2008) and isolated rabbit eye (IRE) (ICCVAM, 2006, 
2010a) tests and data from approaches using two or more in vitro tests. 
However, NICEATM requests data from other tests including, but not 
limited to, the bovine corneal opacity and permeability (BCOP), 
isolated chicken eye (ICE), hen's egg test--chorioallantoic membrane 
(HET-CAM), Cytosensor microphysiometer (CM), fluorescein leakage (FL), 
SkinEthicTM human corneal epithelium, and 
EpiOcularTM tests. If available, corresponding in vivo data 
for these substances are also requested, including data from any 
ethical human or animal studies or accidental human exposures.

DATES: Nominations and test method data for the STE and IRE tests 
should be submitted by August 27, 2012. Data submitted after this date 
will be considered in the evaluation where feasible.

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 development of in vitro alternatives to animals for eye safety 
assessments is an ICCVAM priority (ICCVAM, 2008). See http://iccvam.niehs.nih.gov/methods/ocutox/ocutox.htm for more information on 
ICCVAM evaluations of ocular toxicity test methods. An efficient non-
animal evaluation of substances for their eye hazard potential is 
expected to require a number of adequately validated in vitro tests 
that can be considered for use in integrated testing and decision 
strategies. In vivo reference data and in vitro test data for available 
methods is sought to support the validity of individual methods and to 
construct integrated testing and decision strategies using multiple 
methods.
    In 2006, ICCVAM evaluated the validation status of the in vitro 
tests BCOP, ICE, HET-CAM, and IRE for their usefulness and limitation 
for identifying ocular corrosives and severe irritants (ICCVAM, 2006). 
ICCVAM concluded that BCOP and ICE had sufficient relevance and 
reliability to support their use for identifying certain types of 
substances as ocular corrosives and severe irritants for regulatory 
hazard classification. Subsequently, BCOP and ICE were adopted as 
Organisation for Economic Co-operation and Development (OECD) Test 
Guidelines 437 and 438, respectively (OECD, 2009a, 2009b). The IRE and 
HET-CAM tests lacked sufficient data and/or had insufficient relevance 
and reliability to support their use for regulatory hazard 
classification.
    In 2009, ICCVAM evaluated the validation status of these four in 
vitro tests for identifying eye injury hazard potential, along with the 
CM test, to assess their usefulness for identifying nonsevere eye 
irritants and substances not classified as irritants (ICCVAM, 2010a). 
ICCVAM concluded that the CM test could be used as a screening test to 
identify some types of substances that may cause permanent or severe 
eye injuries. ICCVAM also recommended that the CM test could be used to 
determine if some types of substances will not cause sufficient injury 
to require hazard classification for eye irritation. The predictivity 
of the remaining four in vitro tests was considered insufficient to 
support their use for identifying substances that may cause reversible 
and nonsevere eye injuries.
    ICCVAM also evaluated the validation status of the antimicrobial 
cleaning products (AMCP) testing strategy, which included the BCOP, CM, 
and EpiOcularTM tests. ICCVAM concluded that the data were 
insufficient to adequately demonstrate that the AMCP testing strategy 
can identify all four U.S. Environmental Protection Agency (EPA) eye 
hazard categories (ICCVAM, 2010b). An EPA-implemented voluntary pilot 
program is ongoing to evaluate the use of the AMCP testing strategy for 
eye irritation labeling for certain antimicrobial products (http://www.epa.gov/oppad001/eye-irritation.pdf).
    The IRE test is an organotypic test method that evaluates the eye 
injury potential of a test substance by measuring corneal opacity, 
corneal swelling, epithelial integrity, and fluorescein staining. 
During the previous evaluations of the IRE test, ICCVAM recommended 
further standardization of the test protocol and additional studies 
using all four endpoints to expand the IRE test validation database 
(ICCVAM, 2006, 2010a).
    The STE test measures the viability of rabbit corneal epithelial 
cells following test substance exposure (Takahashi et al., 2008). 
NICEATM is requesting additional data that can be considered in 
assessing the validity of the STE and the IRE. Other test methods and 
integrated testing and decision strategies will also be considered for 
review if there are sufficient new data available.
    For test methods and strategies for which there are sufficient 
data, ICCVAM will develop draft recommendations on test method 
usefulness and limitations, standardized test method protocols, future 
studies that may expand the usefulness of the test method, and test 
method performance standards. These draft recommendations and 
supporting data will be provided to the Panel and made available to the 
public. The Panel will meet in public session to review the validation 
status of the proposed methods and comment on the extent to which the 
data support the draft ICCVAM test method recommendations. Meeting 
information, including dates, locations, and public availability of the 
meeting documents will be announced in a future Federal Register notice 
and will also be posted on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov).

Request for Nominations of Scientific Experts

    NICEATM requests nominations of scientists with relevant knowledge 
and expertise to serve on the Panel. Areas of relevant expertise 
include, but are not limited to biostatistics; human and veterinary 
ophthalmology, with an emphasis on evaluation and treatment of chemical 
injuries; in vivo eye safety testing; in vitro eye safety testing; and 
test method validation. Each nomination should include the nominee's 
name, affiliation, contact information (i.e., mailing address, email 
address, telephone and fax numbers), curriculum vitae, and a brief 
summary of relevant experience and qualifications.

Request for Data

    NICEATM invites the submission of data from substances tested in 
any in vitro test and integrated non-animal

[[Page 41408]]

testing strategies proposed for identifying eye injury hazard potential 
of chemicals and products. If available, in vivo reference data for 
substances tested in these data sets are also requested. Although data 
can be accepted at any time, please submit data by August 27, 2012 to 
ensure consideration during the ICCVAM evaluation process. Relevant 
data received after this date will be considered where feasible. All 
information submitted in response to this notice will be made publicly 
available and may be incorporated into future NICEATM and ICCVAM 
reports and publications, as appropriate.
    When submitting data, please reference this Federal Register notice 
and provide appropriate contact information (name, affiliation, mailing 
address, phone, fax, email, and sponsoring organization, as 
applicable). NICEATM prefers that data be submitted as copies of pages 
from study notebooks and/or study reports, if available. Laboratory 
data and analyses available in electronic format may also be submitted. 
Each submission for a substance should preferably include the following 
information, as appropriate: common and trade name, Chemical Abstracts 
Service Registry Number (CASRN), commercial source, in vitro test 
protocol used, rabbit eye test protocol used, individual animal or in 
vitro responses at each observation time (i.e., raw data), extent to 
which the data were collected in accordance with national or 
international Good Laboratory Practice guidelines, date and testing 
organization, and physical and chemical properties (e.g., molecular 
weight, pH, water solubility, etc.)

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 and integrated testing strategies with 
regulatory applicability and promotes the scientific validation and 
regulatory acceptance of testing methods that more accurately assess 
the safety and hazards of chemicals and products and that reduce, 
refine (enhance animal well-being and lessen or avoid 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 welcome the public 
nomination of new, revised, and alternative test methods and strategies 
for validation studies and technical evaluations. Additional 
information about NICEATM and ICCVAM 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. 2008. The NICEATM-ICCVAM Five-Year Plan (2008-2012): A Plan 
to Advance Alternative Test Methods of High Scientific Quality to 
Protect and Advance the Health of People, Animals, and the Environment. 
NIH Publication No. 08-6410. Research Triangle Park, NC: NIEHS. 
Available: http://iccvam.niehs.nih.gov/docs/5yearplan.htm.
    ICCVAM. 2010a. 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. 2010b. 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/antimicro/TMER.htm.
    OECD. 2009a. Test Guideline 437. Bovine Corneal Opacity and 
Permeability Test Method for Identifying Ocular Corrosives and Severe 
Irritants [adopted 7 September 2009]. In: OECD Guidelines for the 
Testing of Chemicals, Section 4: Health Effects. Paris:OECD Publishing. 
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 No. 438. Isolated Chicken Eye Test Method for 
Identifying Ocular Corrosives and Severe Irritants [adopted 7 September 
2009]. In: OECD Guidelines for Testing of Chemicals. Paris:OECD 
Publishing. Available: http://www.oecd-ilibrary.org/environment/test-no-438-isolated-chicken-eye-test-method-for-identifying-ocular-corrosives-and-severe-irritants_9789264076310-en.

Takahashi Y, Koike M, Honda H, Ito Y, Sakaguchi H, Suzuki H, Nishiyama 
N. 2008. Development of the short time exposure (STE) test: an in vitro 
eye irritation test using SIRC cells. Toxicol In Vitro 22:760-770.

    Dated: July 5, 2012.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2012-17118 Filed 7-12-12; 8:45 am]
BILLING CODE 4140-01-P