Federal Register, Volume 77 Issue 135 (Friday, July 13, 2012)

[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),
SkinEthic^TM human corneal epithelium, and
EpiOcular^TM 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 EpiOcular^TM 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