[Federal Register Volume 74, Number 132 (Monday, July 13, 2009)]
[Notices]
[Pages 33444-33445]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-16388]


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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); Independent 
Scientific Peer Review Panel Report: Evaluation of the Validation 
Status of Alternative Ocular Safety Testing Methods and Approaches: 
Notice of Availability and Request for Public Comments

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

ACTION: Request for comments.

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SUMMARY: NICEATM, in collaboration with the Interagency Coordinating 
Committee on the Validation of Alternative Methods (ICCVAM), convened 
an independent international scientific peer review panel (hereafter, 
Panel) on May 19-21, 2009, to evaluate test methods and approaches with 
the potential to reduce and refine the use of animals for ocular safety 
testing. These evaluations included the following:
     A proposal for the routine use of topical anesthetics, 
systemic analgesics, and humane endpoints to avoid and minimize pain 
and distress during in vivo ocular irritation testing.
     The in vivo low volume eye test (LVET).
     The use of the bovine corneal opacity and permeability 
(BCOP), the Cytosensor Microphysiometer[reg] (CM), the isolated chicken 
eye (ICE), the isolated rabbit eye (IRE), and the hen's egg test--
chorioallantoic membrane (HET-CAM) test methods for identifying 
moderate and mild ocular irritants and substances not labeled as ocular 
irritants.
     Nonanimal testing strategies that use the BCOP, CM, and/or 
EpiOcularTM (EO) test methods to assess the eye irritation 
potential of antimicrobial cleaning products to determine their 
appropriate U.S. Environmental Protection Agency ocular hazard 
classification.
    The Panel report from this meeting is now available. The report 
contains (1) The Panel's evaluation of the validation status of the 
test methods and testing strategies and (2) the Panel's comments on the 
draft ICCVAM test method recommendations. NICEATM invites public 
comment on the Panel report. The report is available on the NICEATM-
ICCVAM Web site at http://iccvam.niehs.nih.gov/docs/ocutox_docs/OcularPRPRept2009.pdf or by contacting NICEATM at the address given 
below.

DATES: Written comments on the Panel report should be received by 
August 28, 2009.

ADDRESSES: NICEATM prefers that comments be submitted electronically by 
e-mail to [email protected]. Comments can also be submitted via the 
NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/contact/FR_pubcomment.htm. Written comments can be sent by mail or fax to Dr. 
William S. Stokes, Director, NICEATM, NIEHS, P.O. Box 12233, Mail Stop: 
K2-16, Research Triangle Park, NC 27709; (fax) 919-541-0947. Courier 
address: NIEHS, NICEATM, 530 Davis Drive, Room 2035, Durham, NC 27713.

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, (telephone) 
919-541-2384, (fax) 919-541-0947 and (e-mail) [email protected].

SUPPLEMENTARY INFORMATION:

Background

    NICEATM announced the convening of an independent scientific peer 
review

[[Page 33445]]

panel to review and comment on the draft background review documents 
(BRDs) and summary review documents (SRDs) and draft recommendations, 
as well as the availability of the draft documents for public comment, 
in March 2009 (74 FR 14556). The Panel met in public session on May 19-
21, 2009, at Consumer Product Safety Commission Headquarters in 
Bethesda, MD. The Panel reviewed the draft ICCVAM documents for 
completeness, errors, and omissions of any existing relevant data or 
information. The Panel then evaluated the information in the draft 
documents to determine the extent to which each of the applicable 
criteria for validation and acceptance of toxicological test methods 
(ICCVAM 2003) had been appropriately addressed. The Panel then 
considered the ICCVAM draft recommendations and commented on the extent 
that the recommendations were supported by the information provided in 
the draft BRDs or SRDs.
    ICCVAM organized a 2005 symposium (70 FR 18037) on Minimizing Pain 
and Distress in Ocular Toxicity Testing where experts recommended that 
topical anesthetics and systemic analgesics should be routinely 
administered before in vivo ocular safety testing to avoid or minimize 
pain and distress that might occur during and after the initial 
application of test substances. The experts also recommended that 
systemic analgesics should routinely be administered when there are 
clinical signs indicative of pain or distress. The experts further 
recommended that humane endpoints to end a study early should be 
identified and used routinely. ICCVAM requested data (72 FR 26396), 
compiled available information on the use of topical anesthetics, 
systemic analgesics, and humane endpoints during in vivo ocular safety 
testing, and developed draft recommendations for implementing such 
practices.
    In 2007, ICCVAM published (70 FR 66451) recommendations on the use 
of four in vitro test methods (BCOP, ICE, IRE, HET-CAM) for identifying 
ocular corrosives and severe irritants for hazard classification and 
labeling purposes. The ICCVAM recommendations were submitted to and 
accepted by ICCVAM member agencies (more information at http://iccvam.niehs.nih.gov/methods/ocutox/ivocutox/ocu_recommend.htm). One 
of the ICCVAM recommendations was to consider the validation status of 
these four in vitro ocular test methods for identifying mild and 
moderate ocular irritants and substances not classified as ocular 
irritants. NICEATM and ICCVAM requested data (72 FR 31582), compiled 
available information, prepared draft BRDs assessing their current 
validation status for this purpose, and developed draft recommendations 
for their use.
    In January 2008, a BRD titled, An In Vitro Approach for EPA 
Labeling of Anti-Microbial Cleaning Products, was submitted to NICEATM 
for review. This BRD, prepared by the Institute for In Vitro Sciences 
in collaboration with the Alternative Testing Working Group (comprised 
of seven consumer product companies [Clorox, Colgate Palmolive, Dial, 
EcoLabs, Johnson Diversey, Procter and Gamble, and SC Johnson]), 
proposes a testing strategy that uses the CM [supreg], 
EpiOcularTM, and BCOP test methods to assess the eye 
irritation potential of antimicrobial cleaning products and to 
determine appropriate EPA ocular hazard classification categories for 
such products. NICEATM and ICCVAM reviewed the BRD, requested 
additional data and information (73 FR 18535), and compiled draft 
recommendations and a draft ICCVAM SRD. ICCVAM also reviewed the 
validation status of the LVET, which is proposed as a reference test 
method to partially substantiate the validity of the in vitro test 
methods used in the test strategy.

Availability of the Peer Panel Report

    The Panel's conclusions and recommendations are detailed in the 
Independent Scientific Peer Review Panel Report: Evaluation of the 
Validation Status of Alternative Ocular Safety Testing Methods and 
Approaches which is available along with the draft documents reviewed 
by the Panel and the draft ICCVAM test method recommendations at http://iccvam.niehs.nih.gov/methods/ocutox/PeerPanel09.htm.

Request for Public Comments

    NICEATM invites the submission of written comments on the Panel 
report. When submitting written comments, please refer to this Federal 
Register notice and include appropriate contact information (name, 
affiliation, mailing address, phone, fax, e-mail, and sponsoring 
organization, if applicable). All comments received will be made 
publicly available via the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/ocutox/PeerPanel09.htm. ICCVAM will 
consider the Panel report along with public comments and comments made 
by the Scientific Advisory Committee on Alternative Toxicological 
Methods (SACATM) at their June 25-26, 2009 meeting (74 FR 19562) when 
finalizing test method recommendations. Final ICCVAM recommendations 
will be published in ICCVAM test method evaluation reports, which will 
be forwarded to relevant Federal agencies for their consideration. The 
evaluation reports will also be available to the public on the NICEATM-
ICCVAM Web site at http://iccvam.niehs.nih.gov/methods/ocutox/ocutox.htm and by request from NICEATM (see ADDRESSES above).

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 
(42 U.S.C. 285l-3) 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 (67 FR 11358). SACATM 
provides advice to the Director of the NIEHS, ICCVAM, and 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).

Reference

ICCVAM. 2003. ICCVAM Guidelines for the Nomination and Submission of 
New, Revised, and Alternative Test Methods. NIH Publication No. 03-
4508. Research Triangle Park, NC: NIEHS. Available at: http://iccvam.niehs.nih.gov.

    Dated: July 3, 2009.
John R. Bucher,
Associate Director, NTP.
[FR Doc. E9-16388 Filed 7-10-09; 8:45 am]
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