[Federal Register Volume 72, Number 226 (Monday, November 26, 2007)]
[Notices]
[Pages 65964-65965]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-22906]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP); NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Availability 
of the Interagency Coordinating Committee on the Validation of 
Alternative Methods (ICCVAM) Test Method Evaluation Report on In Vitro 
Ocular Toxicity Test Methods for Identifying Severe Irritants and 
Corrosives and Final In Vitro Ocular Test Method Background Review 
Documents; Notice of Transmittal of ICCVAM Test Method Recommendations 
to Federal Agencies

AGENCY: National Institute of Environmental Health Sciences (NIEHS), 
National Institutes of Health (NIH).

ACTION: Availability of ICCVAM Test Method Evaluation Report and Final 
Background Review Documents.

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SUMMARY: NICEATM announces availability of the ICCVAM Test Method 
Evaluation Report: In Vitro Ocular Toxicity Test Methods for 
Identifying Severe Irritants and Corrosives (NIH Publication 07-4517). 
The report describes four ocular toxicity test methods evaluated by 
ICCVAM: (1) The Bovine Corneal Opacity and Permeability [BCOP] test, 
(2) the Isolated Chicken Eye [ICE] test, (3) the Isolated Rabbit Eye 
[IRE] test, and (4) the Hen's Egg Test--Chorioallantoic Membrane [HET-
CAM]. The report includes ICCVAM's (a) final test method 
recommendations on the use of these four in vitro test methods, (b) 
recommended test method protocols for future testing, (c) 
recommendations for further optimization and validation studies for 
these test methods, and (d) recommended reference substances for 
validation studies. The report recommends that the BCOP and ICE 
methods, with specific limitations for certain chemical classes and/or 
physical properties, can be used in a tiered testing strategy to 
determine ocular hazards, and substances that test positive can be 
classified as ocular corrosives or severe irritants without further 
testing in animals. The report also recommends that these in vitro test 
methods should be considered before using animals for ocular testing 
and used when determined appropriate.
    NICEATM also announces availability of the final Background Review 
Documents (BRDs) for the BCOP, ICE, IRE, and HET-CAM test methods (NIH 
Publications 06-4512, 06-4513, 06-4514, and 06-4515, respectively). 
These BRDs provide the data and analyses used to assess the current 
validation status of these four test methods for identifying ocular 
corrosives and severe irritants.
    Electronic copies of the ICCVAM Test Method Evaluation Report and 
the four BRDs are available from the NICEATM/ICCVAM Web site at http://iccvam.niehs.nih.gov or by contacting NICEATM (see FOR FURTHER 
INFORMATION CONTACT). The ICCVAM Test Method Evaluation Report and the 
final BRDs have been forwarded to U.S. Federal agencies for regulatory 
and other acceptance considerations where applicable. Responses will be 
posted on the ICCVAM/NICEATM Web site as they are received.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director, 
NICEATM,

[[Page 65965]]

NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC 27709, 
(phone) 919-541-2384, (fax) 919-541-0947, (e-mail) 
[email protected]. Courier address: NICEATM, NIEHS, 79 T.W. 
Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC 
27709.

SUPPLEMENTARY INFORMATION: 

Background

    In 2003, the Scientific Advisory Committee on Alternative 
Toxicological Methods (SACATM) and U.S. Environmental Protection Agency 
(EPA) recommended that ICCVAM review the validation status of screening 
test methods that could be used to identify severe and irreversible 
ocular effects. ICCVAM unanimously agreed that the four in vitro test 
methods (IRE, ICE, BCOP, and HET-CAM) nominated by EPA should have high 
priority for evaluation. On March 24, 2004, NICEATM published a Federal 
Register notice (Vol. 69, No. 57, pp. 13859-13861) requesting all 
available data on these four in vitro ocular irritancy test methods and 
corresponding data from in vivo rabbit eye test methods, as well as any 
human exposure data (obtained either from ethical human studies or by 
accidental exposure). NICEATM subsequently compiled data and 
information on each test method and released four draft BRDs for public 
comment on November 3, 2004 (Federal Register, Vol. 69, No. 212, pp. 
64081-64082).
    On January 11-12, 2005, NICEATM, on behalf of ICCVAM, convened an 
expert panel meeting to independently assess the validation status of 
these four test methods. The panel's report was released in March 2005 
(Federal Register, Vol. 70, No. 53, pp 13513). Public comments at this 
meeting indicated that additional data on these in vitro test methods 
could be made available; therefore, the panel recommended that NICEATM 
obtain the additional data and reanalyze the accuracy and reliability 
of each test method. On February 28, 2005, NICEATM again solicited in 
vitro data on these four test methods and corresponding in vivo data 
(Federal Register, Vol. 70, No. 38, pp. 9661-9662). The revised 
analyses were published on July 26, 2005, as an addendum to the draft 
BRDs (Federal Register, Vol. 70, No. 142, pp. 43149).
    NICEATM, on behalf of ICCVAM, reconvened the panel on September 19, 
2005, to discuss the addendum to the draft BRDs (Federal Register, Vol. 
70, No. 174, pp. 53676-53677). An addendum to the panel report was 
published in November 2005 (Federal Register, Vol. 70, No. 211, pp. 
66451). At its December 2005 meeting, the SACATM discussed and provided 
comments on the panel report and addendum (Federal Register, Vol. 70, 
No. 216, pp. 68069-68070) (minutes from that meeting are available at 
http://ntp.niehs.nih.gov/go/8202).
    ICCVAM considered the expert panel report and its addendum, public 
comments, SACATM comments, and the draft BRDs and their addendums in 
finalizing its recommendations on the validation status of these four 
test methods. The ICCVAM Test Method Evaluation Report includes the 
ICCVAM recommendations on the use of each test method, as well as 
recommended test method protocols, recommendations for further 
optimization and validation studies, recommended reference substances 
for future validation studies, the panel report and its addendum, and 
Federal Register notices. The four final BRDs, which provide the 
supporting documentation for this report, are available as separate 
documents. The ICCVAM Test Method Evaluation Report and the supporting 
final BRDs were forwarded to U.S. Federal agencies for their 
consideration for regulatory acceptance as required by the ICCVAM 
Authorization Act of 2000 (42 U.S.C. 285l-3). Agencies' responses to 
the test method recommendations will be posted on the ICCVAM/NICEATM 
Web site as they are received.

Background Information on ICCVAM, NICEATM, and SACATM

    ICCVAM is an interagency committee composed of representatives from 
15 Federal regulatory and research agencies that use, generate, or 
disseminate 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 
established ICCVAM as a permanent interagency committee of the NIEHS 
under NICEATM. NICEATM administers ICCVAM and provides scientific and 
operational support for ICCVAM-related activities. NICEATM and ICCVAM 
work collaboratively to evaluate new and improved test methods 
applicable to the needs of U.S. Federal agencies. Additional 
information about ICCVAM and NICEATM can be found on their Web site 
(http://iccvam.niehs.nih.gov).
    SACATM was established January 9, 2002, and is composed of 
scientists from the public and private sectors (Federal Register, Vol. 
67, No. 49, page 11358). SACATM provides advice to the Director of the 
NIEHS, to ICCVAM, and to NICEATM regarding the statutorily mandated 
duties of ICCVAM and activities of NICEATM. Additional information 
about SACATM, including the charter, roster, and records of past 
meetings, can be found at http://ntp.niehs.nih.gov/ see ``Advisory 
Board & Committees'' (or directly at http://ntp.niehs.nih.gov/go/167).

    Dated: November 13, 2007.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
 [FR Doc. E7-22906 Filed 11-23-07; 8:45 am]
BILLING CODE 4140-01-P