E9-7220. National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM); Announcement of an Independent Scientific Peer Review Panel on Alternative Ocular Safety Testing Methods; ...

AGENCY:

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

ACTION:

Meeting announcement and request for comments.

SUMMARY:

NICEATM, in collaboration with the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), announces a public meeting of an independent scientific peer review panel (Panel) on alternative ocular safety testing methods. The Panel will evaluate (1) the validation status of a testing strategy that proposes the use of three in vitro test methods to assess the eye irritation potential of antimicrobial cleaning products (AMCPs), (2) the validation status of four in vitro test methods for identifying moderate (EPA Category II, UN Globally Harmonized System of Classification and Labeling of Chemicals (GHS) Category 2A) and mild (EPA Category III, GHS Category 2B) ocular irritants and substances not classified as ocular irritants (EPA Category IV, GHS Not Classified), (3) the validation status of the in vivo Low Volume Eye Test, and (4) 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 Panel will review draft ICCVAM summary review documents and draft BRDs and evaluate the extent to which established validation and acceptance criteria have been adequately addressed for each proposed test method and strategy. The Panel also will be asked to comment on the extent to which the information included in the BRDs supports ICCVAM's draft test method recommendations.

NICEATM invites public comments on the draft ICCVAM summary review documents, BRDs, and draft ICCVAM test method recommendations. All documents will be available on the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov/​methods/​ocutox/​PeerPanel09.htm. Documents will be posted no later than April 1, 2009.

DATES:

The meeting is scheduled for May 19-21, 2009, from 8:30 a.m. to 5 p.m. each day. The deadline for registration to attend the meeting and submission of written comments is May 15, 2009.

ADDRESSES:

The meeting will be held at the U.S. Consumer Products Safety Commission (CPSC) Headquarters, Bethesda Towers Building, 4330 East West Highway, Bethesda, MD. Persons needing special assistance in order to attend, such as sign language interpretation or other reasonable accommodation, should contact 301-402-8180 (voice) or 301-435-1908 TTY (text telephone) at least seven business days before the event.

FOR FURTHER INFORMATION CONTACT:

Dr. William S. Stokes, Director, NICEATM, NIEHS, P.O. Box 12233, Mail Stop: K2-16, Research Triangle Park, NC 27709; (telephone) 919-541-2384; (fax) 919-541-0947; (e-mail) [e-mail]. Courier address: NICEATM, NIEHS, 530 Davis Drive, Room 2035, Durham, NC 27713.

SUPPLEMENTARY INFORMATION:

Background

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]), describes a testing strategy that uses the Cytosensor Microphysiometer ®, EpiOcular ^TM, and Bovine Corneal Opacity and Permeability (BCOP) assays to assess the eye irritation potential of AMCPs and to determine the appropriate EPA ocular hazard classification category. NICEATM and ICCVAM reviewed the BRD, requested additional data and information, and compiled draft recommendations and a draft ICCVAM summary review document. The Panel will first consider the current validation status of each of the three in vitro test methods and then consider the validation status of the proposed testing strategy. The Panel will also review the validation status of the in vivo Low Volume Eye Test, which is proposed as reference data to partially substantiate the validity of the in vitro test methods used in the test strategy.

ICCVAM previously published recommendations on the use of four in vitro test methods (the BCOP, the isolated chicken eye test method, the isolated rabbit eye test method, and the hen's egg test-choriallantoic membrane test method) for identifying ocular corrosives and severe irritants for hazard classification and labeling purposes (available at http://iccvam.niehs.nih.gov/​methods/​ocutox/​ivocutox/​ocu_​tmer.htm). The ICCVAM recommendations were submitted to and accepted by ICCVAM member agencies (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 have prepared draft BRDs assessing their current validation status for this purpose/application.

ICCVAM developed draft recommendations for the routine use of topical anesthetics, systemic analgesics, and humane endpoints to avoid or minimize pain and distress during in vivo ocular irritation testing. The proposal is based on recommendations by experts at a 2005 symposium Minimizing Pain and Distress in Ocular Toxicity Testing (co-sponsored by NICEATM-ICCVAM, the European Centre for the Evaluation of Alternative Methods [ECVAM], and the European Cosmetics Association) [http://iccvam.niehs.nih.gov/​meetings/​ocumeet/​sympinfo.htm] that topical anesthetics and systemic analgesics should routinely be administered before ocular testing to avoid or minimize pain and distress that might occur during and after the initial application of test articles. The symposium experts also recommended that systemic analgesics should routinely be administered when there is evidence of potentially painful ocular damage or when there are clinical signs indicative of pain or distress. The experts also identified specific ocular injuries that would not be expected to reverse within 21 days, and therefore could be used as humane endpoints to end a study early. ICCVAM requested data (72 FR 26396) and then compiled available information on using topical anesthetics or systemic analgesics. The Panel will review the available information and comment on draft ICCVAM recommendations for the routine use of analgesics, anesthetics, and humane endpoints.

ICCVAM is also cooperating with ECVAM on the peer review evaluation of four cell-based in vitro ocular test methods by an ECVAM Scientific Advisory Committee (ESAC) Peer Review Panel. The four methods, Cytosensor ®, Fluorescein Leakage, Neutral Red Release, and the Red Blood Haemaolysis Test Method, are being evaluated for their usefulness and limitations for identifying ocular corrosives and severe irritants (i.e., EPA Category I, European Union (EU) R41, GHS Category 1) and substances not classified as ocular irritants (i.e., EPA Category IV, EU Not Labeled, GHS Not Classified). ECVAM prepared BRDs for the four methods and links to these documents will be available on the ICCVAM Web site by April 1, 2009. ICCVAM developed draft recommendations on the usefulness and limitations of the four test methods based on the information in the BRDs. Public comments on the BRDs and draft recommendations are invited. The Panel will also be asked to comment on the ICCVAM draft recommendations.

Peer Review Panel Meeting

This meeting will take place May 19-21, 2009, at the CPSC Headquarters, Bethesda Towers Building, 4330 East West Highway, Bethesda, MD. It will begin at 8:30 a.m. and is scheduled to conclude each day at approximately 5 p.m. The meeting is open to the public at no charge, with attendance limited only by the space available. The Panel will consider the draft ICCVAM summary review documents and/or BRDs for each test method and evaluate the extent to which established validation and acceptance criteria are adequately addressed (as described in Validation and Regulatory Acceptance of Toxicological Test Methods: A Report of the ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods, NIH Publication No. 97-3981, available at http://iccvam.niehs.nih.gov/​docs/​about_​docs/​validate.pdf). The Panel will then comment on the extent to which each of the draft ICCVAM test method recommendations is supported by the information provided in the corresponding draft BRD(s). The Panel is expected to review the test methods and testing strategy for labeling AMCPs first, followed by the four test methods used to identify mild and moderate irritants, and finally the use of anesthetics, analgesics, and humane endpoints when conducting in vivo eye irritation tests in rabbits.

Additional information about the meeting, including a roster of the Panel members and the draft agenda, will be posted on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/​methods/​ocutox/​PeerPanel09.htm) two weeks before the meeting. This information will also be available after that date by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT above).

Attendance and Registration

In order to facilitate planning for this meeting, persons wishing to attend are asked to register by May 15, 2009, via the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/​contact/​reg_​form_​OcuPanel.htm). Visitor information, area map, driving directions, and CPSC contact information are available at http://www.cpsc.gov/​about/​contact.html.

Availability of the Documents

The draft summary review documents, draft BRDs, and draft ICCVAM test method recommendations will be posted no later than April 1, 2009, on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/​methods/​ocutox/​PeerPanel09.htm), or by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT above).

Request for Public Comments

NICEATM invites the submission of written comments on the draft ICCVAM summary review documents, draft BRDs, and draft ICCVAM test method recommendations by May 15, 2009. NICEATM prefers that comments be submitted electronically via the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov/​contact/​FR_​pubcomment.htm) or via e-mail to [e-mail]. Written comments may also be sent by mail, fax, or email to Dr. William Stokes, Director, NICEATM, at the address listed above (see FOR FURTHER INFORMATION CONTACT). When submitting written comments, please refer to this Federal Register notice and include appropriate contact information (name, affiliation, mailing address, phone, fax, email, and sponsoring organization, if applicable). NICEATM will post all comments on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov) identified by the individual's name and affiliation or sponsoring organization (if applicable). NICEATM will provide these comments to the Panel and ICCVAM agency representatives and make them available to the public at the meeting.

Opportunity will be provided for members of the public to present oral comments at designated times during the peer review. Up to seven minutes will be allotted per speaker. If you wish to present oral statements at the meeting (one speaker per organization), contact NICEATM (see FOR FURTHER INFORMATION CONTACT above) by May 15, 2009. Please provide a written copy of your comments with contact information (name, affiliation, mailing address, phone, fax, email, and sponsoring organization, if applicable) when registering to make oral comments. If it is not possible to provide a copy of your statement in advance, please bring 40 copies to the meeting for distribution to the Panel and to supplement the record. Written statements can supplement and expand the oral presentation. Please provide NICEATM with copies of any supplementary written statement using the guidelines outlined above.

Summary minutes and the Panel's final report will be available following the meeting on the NICEATM-ICCVAM Web site (http://iccvam.niehs.nih.gov). ICCVAM will consider the Panel's conclusions and recommendations and any public comments received in finalizing their test method recommendations for these methods.

Background Information on ICCVAM and NICEATM

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).

Dated: March 20, 2009.

John R. Bucher,

Associate Director, NTP.