[Federal Register Volume 71, Number 132 (Tuesday, July 11, 2006)]
[Notices]
[Pages 39122-39123]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-10789]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Toxicology Program (NTP), NTP Interagency Center for the 
Evaluation of Alternative Toxicological Methods (NICEATM); Availability 
of Peer Review Panel Report on the Use of In Vitro Basal Cytotoxicity 
Test Methods for Estimating Starting Doses for Acute Oral Systemic 
Toxicity Testing and Request for Comments

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

ACTION: Request for comments.

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SUMMARY: The National Toxicology Program (NTP) Interagency Center for 
the Evaluation of Alternative Toxicological Methods (NICEATM), in 
collaboration with the Interagency Coordinating Committee on the 
Validation of Alternative Methods (ICCVAM), organized an independent, 
scientific peer review meeting on May 23, 2006, to evaluate the 
validation status of the in vitro 3T3 and normal human keratinocyte 
(NHK) neutral red uptake (NRU) basal cytotoxicity test methods. These 
two in vitro cytotoxicity test methods are proposed as adjuncts (for 
the purpose of determining the starting dose) to in vivo acute oral 
toxicity tests. The peer review report from this meeting, entitled Peer 
Review Panel Evaluation of the Use of In Vitro Basal Cytotoxicity Test 
Methods for Estimating Starting Doses for Acute Oral Systemic Toxicity 
Testing, is now available. The report contains (1) a summary of the 
peer review evaluation and (2) the peer review panel's (Panel) 
conclusions on the draft ICCVAM test method recommendations regarding 
the proposed usefulness, limitations, and validation status of the 3T3 
and NHK cytotoxicity test methods. The NICEATM invites public comment 
on the Panel's conclusions on the draft ICCVAM test method 
recommendations. Copies of the Panel report may be obtained on the 
ICCVAM/NICEATM Web site at http://iccvam.niehs.nih.gov, or by 
contacting NICEATM at the address given below.

DATES: Written comments should be received at NICEATM by August 25, 
2006.

ADDRESSES: Public comments and any other correspondence should be sent 
by mail, fax, or e-mail to Dr. William S. Stokes, NICEATM, 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].

SUPPLEMENTARY INFORMATION: 

Background

    The 3T3 and NHK cytotoxicity test methods are proposed as adjuncts 
(for the purpose of determining the starting dose) to in vivo acute 
oral toxicity test methods (i.e., the Up-and-Down Procedure [EPA 2002a; 
OECD 2001a], the Acute Toxic Class method [OECD 2001b]) to refine 
(i.e., to lessen or avoid pain and distress) and/or reduce animal use. 
Both in vitro cytotoxicity test methods have been assessed in a NICEATM 
and European Centre on the Validation of Alternative Methods (ECVAM) 
collaborative independent validation study. At this peer review 
meeting, the Panel reviewed the background review document (BRD) on the 
3T3 and NHK cytotoxicity test methods and evaluated the extent that 
established validation and acceptance criteria had been adequately 
addressed for the intended purpose of the test methods. The Panel also 
provided comments on draft ICCVAM recommendations regarding the 
proposed use of these test methods, draft test method protocols, draft 
performance standards, and draft recommended future studies. The 
Panel's conclusions and recommendations on the two in vitro 
cytotoxicity test methods are described in the Peer Review Panel 
Evaluation of the Use of In Vitro Basal Cytotoxicity Test Methods for 
Estimating Starting Doses for Acute Oral Systemic Toxicity Testing 
(available at http://iccvam.niehs.nih.gov/).
    Prior to the Panel meeting, NICEATM issued Federal Register notices 
to (1) recommend that in vitro basal cytotoxicity test methods be 
considered as tools for estimating starting doses for in vivo acute 
systemic toxicity tests (66FR49686), (2) announce a request for 
nominations for Panel members and submission of existing in vivo and in 
vitro data (70FR14473), (3) announce the independent peer review 
meeting on the use of the 3T3 and NHK cytotoxicity test methods for 
estimating starting doses for acute oral systemic toxicity tests, and 
(4) request comments on the draft BRD and draft ICCVAM recommendations 
(71FR14229). All Federal Register notices, the draft BRD, and the draft 
ICCVAM recommendations are available at http://iccvam.niehs.nih.gov/.

Request for Comments

    NICEATM invites the submission of written comments on the Panel's

[[Page 39123]]

conclusions on the draft ICCVAM test method recommendations. 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 by the deadline listed above will be 
placed on the ICCVAM/NICEATM Web site and made available to ICCVAM. In 
addition, there will be an opportunity for oral public comments on the 
draft ICCVAM test method recommendations for the 3T3 and NHK 
cytotoxicity test methods during a teleconference meeting of the 
Scientific Advisory Committee on Alternative Toxicological Methods 
(SACATM) scheduled for August 3, 2006. Details of the SACATM 
teleconference are published as a separate Federal Register notice 
(available at http://ntp.niehs.nih.gov/go/frn). Any written comments on 
the Panel report received prior to July 25, 2006, will be distributed 
to SACATM.
    ICCVAM will consider the Panel report along with SACATM and public 
comments received on that report as it prepares final ICCVAM 
recommendations for the 3T3 and NHK cytotoxicity test methods. An 
ICCVAM test method evaluation report, which will include the final 
ICCVAM recommendations, will be forwarded to the appropriate federal 
agencies for their consideration. This report also will be available to 
the public on the ICCVAM/NICEATM website and by request from NICEATM.

Background Information on ICCVAM, NICEATM, and SACATM

    ICCVAM is an interagency committee composed of representatives from 
15 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, or replace 
animal use. The ICCVAM Authorization Act of 2000 [42 U.S.C. 285l-3(d)] 
establishes 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 Federal agencies. Additional information 
about ICCVAM and NICEATM can be found at the ICCVAM-NICEATM Web site 
(http://iccvam.niehs.nih.gov).
    SACATM was established January 9, 2002, to fulfill section 3(d) of 
the ICCVAM Authorization Act of 2000 and is composed of scientists from 
the public and private sectors (Federal Register: March 13, 2002: Vol. 
67, No. 49, page 11358). SACATM provides advice to the Director of the 
NIEHS, ICCVAM, and NICEATM regarding 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/go/167.

References

EPA. 2002. Health Effects Test Guidelines OPPT 870.1100 Acute Oral 
Toxicity. EPA 712-C-02-190. Washington, DC: U.S. Environmental 
Protection Agency. Available at: http://www.epa.gov/opptsfrs/publications/.
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.
OECD. 2001a. Guideline for Testing of Chemicals, 425, Acute Oral 
Toxicity--Up-and-Down Procedure. Paris, France:OECD. Available at: 
http://www.oecd.org.
OECD. 2001b. Guideline for Testing of Chemicals, 423, Acute Oral 
Toxicity--Acute Toxic Class Method. Paris, France:OECD. Available 
at: http://www.oecd.org.

    Dated: June 30, 2006.
Samuel H. Wilson,
Deputy Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
 [FR Doc. E6-10789 Filed 7-10-06; 8:45 am]
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