[Federal Register Volume 69, Number 57 (Wednesday, March 24, 2004)]
[Notices]
[Pages 13859-13861]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-6487]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
National Toxicology Program (NTP); National Institute of
Environmental Health Sciences (NIEHS); National Institutes of Health
(NIH); NTP Interagency Center for the Evaluation of Alternative
Toxicological Methods (NICEATM); Request for Public Comment on the
Nomination for Ocular Toxicity Test Methods and Related Activities and
Request for Data on Chemicals Evaluated by In Vitro or In Vivo Ocular
Irritancy Test Methods
SUMMARY: On behalf of the Interagency Coordinating Committee on the
Validation of Alternative Methods (ICCVAM), NICEATM requests (1) public
comment on four test methods for ocular toxicity and related activities
nominated to the ICCVAM by the U.S. Environmental Protection Agency
(EPA), (2) public comment on ICCVAM's recommended actions for the
nomination, and (3) data from completed studies on chemicals and
products tested for ocular irritancy using in vitro and/or in vivo test
methods. This data will be used to (1) evaluate the validation status
of existing in vitro test methods for ocular irritancy/corrosion and
(2) develop a list of substances with high quality in vivo data that
can be considered as reference chemicals for future validation studies.
NICEATM welcomes data generated using standardized in vitro test
methods used to identify severe, moderate, mild, or non-irritating
substances. Test methods for identifying severe (irreversible) ocular
irritation/corrosion for which data are sought include, but are not
limited to the four methods nominated by the EPA: (1) The Bovine
Corneal Opacity and Permeability (BCOP) test, (2) the Isolated Rabbit
Eye (IRE) test or the Rabbit Enucleated Eye Test (REET), (3) the
Isolated Chicken Eye (ICE) test or the Chicken Enucleated Eye Test
(CEET), and (4) the Hen's Egg Test--Chorion Allantoic Membrane (HET-
CAM). In addition, high quality data from standardized ocular irritancy
test methods using rabbits (e.g., EPA 1998; UN 2003) and in vivo data
generated from procedures/protocols that might alleviate or reduce pain
and suffering (e.g., topical and systemic analgesics) in test animals
are requested.
Background Information
The Scientific Advisory Committee on Alternative Toxicological
Methods (SACATM) unanimously recommended at its meeting in August 2003
that NICEATM focus efforts on test methods for ocular irritancy and
possibly hold a workshop and/or develop a background document on
available methods. In October 2003, the EPA nominated the following
activities to ICCVAM: (1) Evaluate the validation status of four in
vitro ocular toxicity test methods: the BCOP, IRE or the REET, ICE or
CEET, and HET-CAM, (2) identify and develop in vivo ocular toxicity
reference data to support the validation of in vitro test methods, (3)
explore ways of alleviating pain and suffering from current in vivo
ocular toxicity testing, and (4) review the state of the science and
the availability of in vitro test methods for assessing mild or
moderate ocular irritants. ICCVAM endorsed the review of the methods as
a high priority and recommended that NICEATM develop Background Review
Documents for BCOP, IRE, ICE, and HET-CAM. ICCVAM also recommended that
NICEATM convene an expert panel to independently review the validation
status of these four methods and propose standardized protocols for
these test methods.
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As part of the nomination review process, the NICEATM invites
public comments on the EPA nomination to ICCVAM and the ICCVAM's
recommended actions. In addition, ICCVAM and NICEATM are collaborating
with the European Center for the Validation of Alternative Methods
(ECVAM) to evaluate the validation status of in vitro methods for
assessing ocular irritation/corrosion. In response to the SACATM
recommendation, the EPA nomination and ICCVAM's recommended actions,
and the NICEATM/ICCVAM collaboration with ECVAM, NICEATM also requests
the submission of data from completed studies on chemicals and products
tested for ocular irritancy using in vitro and/or in vivo test methods.
This data will be used to evaluate the validation status of existing in
vitro test methods for ocular irritancy/corrosion and to develop a list
of substances with high quality in vivo data that can be considered as
reference chemicals for future validation studies. Information on the
expert panel evaluation(s) will be announced in a future Federal
Register notice.
Public Comment and Submission of Chemical and Protocol Information and
Test Data
Public comment and data and other information submitted in response
to this notice should be sent to NICEATM (Dr. William S. Stokes,
Director, NICEATM, NIEHS, 79 T.W. Alexander Drive, P.O. Box 12233, MD
EC-17, Research Triangle Park, NC 27709, (phone) 919-541-2384, (fax)
919-541-0947, [email protected]) and received by May 24, 2004. Data
and other information received by this date will be forwarded to the
ICCVAM and the ICCVAM Ocular Toxicity Working Group (OTWG) for their
consideration. Data and other information received after this date will
be periodically compiled and added to the database maintained by
NICEATM. All information submitted in response to this notice will be
made publicly available upon request to NICEATM.
When submitting data or information on protocols, please reference
this Federal Register notice and provide appropriate contact
information (name, affiliation, mailing address, phone, fax, e-mail,
and sponsoring organization, as applicable). NICEATM prefers data to be
submitted as copies of pages from applicable study notebooks and/or
study reports, if available. Each submission for a chemical should
preferably include the following information, as appropriate:
Common and trade name;
Chemical Abstracts Service Registry Number
(CASRN);
Chemical and/or product class;
Commercial source;
In vitro test protocol used;
Rabbit eye test protocol used;
Human eye test protocol used;
Individual animal/human or in vitro responses at
each observation time (i.e., raw data);
The extent to which the study complies with
national/international Good Laboratory Practice (GLP) guidelines;
Date and testing organization.
Those persons submitting data on chemicals tested for ocular
irritancy in rabbits are referred to the ICCVAM/NICEATM Web site
(http://iccvam.niehs.nih.gov/methods/eyeirrit.htm) for an example of
the type of experimental animal study information and data requested in
this notice.
In Vitro Ocular Irritancy Chemical Tests: BCOP, HET-CAM, ICE, and IRE
NICEATM welcomes public comment on and the submission of data from
the four in vitro test methods used to identify severe (irreversible)
ocular irritation/corrosion nominated by the EPA: BCOP, HET-CAM, ICE,
and IRE. This information will be used to evaluate the validation
status of these test method protocols and to identify any additional
development and/or validation that might be helpful in advancing the
usefulness of the proposed test methods. ICCVAM anticipates
recommending a standardized protocol for each of the four test methods.
ICCVAM also will use existing data and protocols as the basis for
development of proposed performance standards that structurally and
functionally similar test methods should meet or exceed. Because test
methods for identifying severe eye irritants/corrosives are of high
priority, NICEATM especially requests data on chemicals identified by
these four methods as severe irritants, although data on mildly
irritating and non-irritating substances also are welcome.
Other In Vitro Ocular Irritancy Methods
NICEATM also requests the submission of data and information for
standardized in vitro ocular irritancy methods, other than the four
identified above, and methods that might accurately identify non-
irritating and mild to moderate irritants. Detailed test method
protocols and other related information for these potential test
methods should be submitted along with the data.
In Vivo Test Methods for Ocular Irritancy
NICEATM requests the submission of high quality in vivo data that
might be used to identify appropriate reference chemicals for future
validation studies of in vitro ocular irritancy test methods. This data
would be used to construct a database of in vivo data to assess
interlaboratory variability, as well as to support validation efforts.
Data are sought from studies conducted to comply with Federal or other
national/international testing requirements, but may not be publicly
available because: (1) The data were submitted to regulatory
authorities, but are proprietary and cannot be released to the public
by regulatory authorities or (2) there is no requirement to submit the
data to regulatory authorities. In addition to data from studies in
animals, NICEATM also welcomes the submission of data from human
studies, including any human post-marketing or occupational exposure/
surveillance data that might be available.
Procedures for Reducing or Eliminating Pain and Suffering during In
Vivo Ocular Irritancy Testing
NICEATM requests the submission of information and data from in
vivo methods, procedures, and/or strategies that may reduce or
eliminate the pain and suffering associated with current in vivo eye
irritation methods, such as those using topical or systemic analgesics.
Background Information on ICCVAM and NICEATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that use or generate
toxicological information. ICCVAM promotes the development, validation,
evaluation, and regulatory acceptance of toxicological test methods
that improve agencies' ability to make decisions on health risks, while
refining, reducing and replacing animal use wherever possible.
The ICCVAM Authorization Act of 2000 (Pub. L. 106-545, available at
http://iccvam.niehs.nih.gov/about/PL106545.htm) establishes ICCVAM as a
permanent interagency committee of the NIEHS under the NICEATM. NICEATM
provides scientific support for ICCVAM and ICCVAM-related activities.
NICEATM and ICCVAM work collaboratively to evaluate new and improved
test methods applicable to the needs of Federal agencies. Additional
information about ICCVAM and
[[Page 13861]]
NICEATM can be found at the following Web site: http://iccvam.niehs.nih.gov.
References
EPA 1998. Health Effects Test Guidelines, OPPTS 870.2500, Acute Eye
Irritation, EPA 712-C-98-195. Available: http://www.epa.gov.opptsfrs/OPPTS_Harmonized/870_Health_Effects_Test_Guidelines/Drafts/870-2400.pdf.
UN. 2003. Globally Harmonized System of Classification and
Labelling of Chemicals (GHS). (ST/SG/AC.10/30). United Nations, New
York and Geneva. Available: http://www.unece.org/trans/danger/publi/ghs/officialtext.html.
Dated: March 15, 2004.
Kenneth Olden,
Director, National Institute of Environmental Health Sciences.
[FR Doc. 04-6487 Filed 3-23-04; 8:45 am]
BILLING CODE 4140-01-P