[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.

[[Page 13860]]

    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