[Federal Register Volume 70, Number 38 (Monday, February 28, 2005)]
[Notices]
[Pages 9661-9662]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-3831]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES


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); Second Request for Data on Chemicals 
Evaluated by In Vitro or In Vivo Ocular Irritancy Test Methods

Summary

    The Interagency Coordinating Committee on the Validation of 
Alternative Methods (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. Data was previously requested (Federal Register, 
Vol. 69, No. 57, pp. 13859-13861, March 24, 2004, available at http://iccvam.niehs.nih.gov/ gov/) and used to prepare draft Background Review 
Documents (BRD) for four methods [(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)], and to compile a database 
of in vivo data. ICCVAM and NICEATM are now finalizing these BRDs and 
want to ensure the inclusion of all available data. NICEATM is 
therefore issuing this second request for data generated using 
standardized in vitro and in vivo 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: (1) The BCOP test; (2) 
the IRE test; (3) the ICE test; and (4) the 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 analgesic) in test animals are requested. 
These 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. Data 
from other in vitro methods used to assess reversible ocular irritation 
effects or non-irritation are also requested.

Submission of Chemical and Protocol Information and Test Data

    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 March 30, 2005. Data and other 
information received by this date will be compiled and added to the 
database maintained by NICEATM and utilized where appropriate for the 
final BRDs on the four methods listed above. Data received after this 
date will also be considered and used where applicable for future 
evaluation activities. 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 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.

[[Page 9662]]

In Vitro Ocular Irritancy Chemical Tests: BCOP, HET-CAM, ICE, and IRE

    NICEATM is especially interested in data from four in vitro test 
methods used to identify severe (irreversible) ocular irritation/
corrosion: BCOP, HET-CAM, ICE, and IRE. 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 are also 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 be used to 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. 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

    In August 2003, the Scientific Advisory Committee on Alternative 
Toxicological Methods (SACATM) unanimously recommended 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 U.S. Environmental Protection Agency nominated the 
following activities to ICCVAM: (1) Evaluate the validation status of 
the four in vitro ocular toxicity test methods (BCOP, IRE, ICE, 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 these methods as a high 
priority and recommended that NICEATM develop Background Review 
Documents for BCOP, IRE, ICE, and HET-CAM. NICEATM convened an 
independent expert panel on January 11-12, 2005, to review the 
validation status of these four methods and develop conclusions and 
recommendations on standardized protocols and reference chemicals for 
future testing and validation studies. Availability of the expert 
panel's report will be announced in a future Federal Register notice.

Background Information on ICCVAM and NICEATM

    ICCVAM is an interagency committee composed of representatives from 
fifteen federal regulatory and research agencies that use or generate 
toxicological information. ICCVAM conducts technical evaluations of 
new, revised, and alternative methods with regulatory applicability, 
and promotes the scientific validation and regulatory acceptance of 
toxicological test methods that more accurately assess the safety and 
hazards of chemicals and products and that refine, reduce, and replace 
animal use. The ICCVAM Authorization Act of 2000 (P.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 administers and provides scientific support 
for the ICCVAM. NICEATM and ICCVAM work collaboratively to evaluate new 
and improved test methods applicable to the needs of federal agencies. 
Additional information about ICCVAM and NICEATM can be found at the 
following Web site: http://www.iccvam.niehs.nih.gov.

References

    EPA 1998. Health Effects Test Guidelines, OPPTS 870.2400, Acute Eye 
Irritation, EPA 712-C-98-195. Available: http://www.epa.gov/opptsfrs/OPPTS_Harmonized/870_Health_Effects_Test_Guidelines/Series/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: February 17, 2005.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences.
[FR Doc. 05-3831 Filed 2-25-05; 8:45 am]
BILLING CODE 4140-01-P