[Federal Register Volume 73, Number 2 (Thursday, January 3, 2008)]
[Notices]
[Pages 493-495]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-25536]


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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); Workshop on 
Acute Chemical Safety Testing: Advancing In Vitro Approaches and Humane 
Endpoints for Systemic Toxicity Evaluations

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

ACTION: Workshop announcement.

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SUMMARY: The Interagency Committee on the Validation of Alternative 
Methods (ICCVAM) and NICEATM announce the upcoming ``Scientific 
Workshop on Acute Chemical Safety Testing: Advancing In Vitro 
Approaches and Humane Endpoints for Systemic Toxicity Evaluations.'' 
The goals of the workshop are to:
    (1) Review the state-of-the-science and identify knowledge gaps 
regarding the key pathways involved in acute systemic toxicity.
    (2) Recommend how these knowledge gaps can be addressed by 
collecting mechanistic biomarker data during currently required in vivo 
safety testing.
    (3) Recommend how key in vivo pathway information can be used to 
develop more predictive mechanism-based in vitro test systems and 
earlier, more humane endpoints for in vivo test methods.
    (4) Recommend how mechanism-based in vitro test systems and 
earlier, more humane endpoints can be used to further reduce, refine, 
and eventually replace animal use for acute systemic toxicity testing 
while ensuring the protection of human and animal health.
    This workshop is open to the public with attendance limited only by 
the space available.

DATES: The workshop will be held on February 6-7, 2008.

ADDRESSES: The workshop will be held at the NIH, Natcher Conference 
Center, 45 Center Drive, Bethesda, MD 20892. A draft agenda and other 
information are available on the ICCVAM workshop Web site (http://iccvam.niehs.nih.gov/meetings/AcuteToxWksp08/AcuteToxWksp08.htm) and 
can be obtained from NICEATM (see FOR FURTHER INFORMATION CONTACT 
below).

FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, NICEATM 
Director, NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC 
27709, (telephone) 919-541-2384, (fax) 919-541-0947, (e-mail) 
[email protected].

SUPPLEMENTARY INFORMATION:

Background

    NICEATM and ICCVAM convened a peer review panel meeting in 2006. 
The panel was charged to determine the

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usefulness and limitations of two in vitro cytotoxicity test methods 
for determining starting doses for two acute oral toxicity test 
methods, the Up-and-Down Procedure and the Acute Toxic Class method, in 
order to reduce the number of animals used in each of these in vivo 
tests. The panel's conclusions and recommendations are described in the 
Peer Review Panel Report: 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/methods/acutetox/inv_nru_scpeerrev.htm). The panel recommended that ICCVAM consider 
convening a working group to explore mechanisms of action for acute 
toxicity and to identify approaches for acquiring additional 
information on acute toxicity mechanisms when conducting required in 
vivo acute toxicity testing. The Scientific Advisory Committee on 
Alternative Toxicological Methods (SACATM) met by teleconference on 
August 3, 2006, and expressed support for the panel's recommendations 
(minutes of that meeting are available at http://ntp.niehs.nih.gov/files/SACATMAug06MinutesVF081506.pdf).
    NICEATM and ICCVAM included activities in their draft Five-Year 
Plan (2008-2012) (http://iccvam.niehs.nih.gov/docs/5yearplan.htm) to 
further reduce animal use and potential pain and distress associated 
with acute toxicity testing. These included organizing an international 
workshop to (1) identify predictive and more humane endpoints that may 
be used to terminate studies earlier in order to further reduce the 
severity and duration of pain and distress and (2) identify and 
standardize procedures for collecting mechanistic information from in 
vivo acute oral toxicity testing that will aid in developing batteries 
of predictive in vitro test methods that can further reduce and 
eventually replace animals for acute toxicity testing.
    The ICCVAM Acute Toxicity Working Group subsequently organized this 
workshop in coordination with NICEATM, the European Centre for the 
Validation of Alternative Methods, and the Japanese Center for the 
Validation of Alternative Methods. The goals of the workshop are to:
    (1) Review the state-of-the-science and identify knowledge gaps 
regarding the key pathways involved in acute systemic toxicity.
    (2) Recommend how these knowledge gaps can be addressed by 
collecting mechanistic biomarker data during currently required in vivo 
safety testing.
    (3) Recommend how key in vivo pathway information can be used to 
develop more predictive mechanism-based in vitro test systems and 
earlier more humane endpoints for in vivo test methods.
    (4) Recommend how mechanism-based in vitro test systems and 
earlier, more humane endpoints can be used to further reduce, refine, 
and replace animal use for acute systemic toxicity testing while 
ensuring the protection of human health.

Workshop Attendance and Registration

    The workshop will be held on February 6-7, 2008, at the NIH Natcher 
Conference Center, 45 Center Drive, Bethesda, MD 20892. Sessions will 
begin at 8 a.m. and end at approximately 5 p.m. on both days. Persons 
needing special assistance in order to attend, such as sign language 
interpretation or other reasonable accommodation, should contact 919-
541-2475 voice, 919-541-4644 TTY (text telephone, through the Federal 
TTY Relay System at 800-877-8339), or e-mail [email protected]. 
Requests should be made at least seven days in advance of the event. 
This workshop is open to the public with attendance being limited only 
by the space available. Individuals who plan to attend are encouraged 
to register in advance with NICEATM. Registration information, an 
agenda, and additional information are available on the workshop Web 
site (http://iccvam.niehs.nih.gov/meetings/AcuteToxWksp08/AcuteToxWksp08.htm) and upon request to NICEATM (see FOR FURTHER 
INFORMATION CONTACT above).

Preliminary Workshop Agenda

Day 1--Wednesday, February 6, 2008

     Opening Plenary Session--Welcome and Overview of Workshop 
Objectives.
     Session 1--Current Acute Systemic Toxicity Injury and 
Toxicity Assessments.
     Session 2--Key Pathways and Biomarkers for Acute Systemic 
Toxicity.
     Concurrent Breakout Group (BG) Discussions:

--BG 1: Acute Systemic Toxicity Injury and Toxicity Assessments.
--BG 2: Key Pathways and Biomarkers for Acute Systemic Toxicity.

     Adjournment.

Day 2--Thursday, February 7, 2008

     Plenary Session--Discussion of Conclusions and 
Recommendations from Breakout Groups 1 and 2.
     Session 3--Developing Earlier Humane Endpoints for Acute 
Systemic Toxicity.
     Session 4--State of the Science: Using In Vitro Methods to 
Predict Acute Systemic Toxicity.
     Concurrent BG Discussions:

--BG 3: Developing Earlier Humane Endpoints for Acute Systemic Toxicity 
Testing.
--BG 4: Applying In Vivo Mechanistic Pathway Information to the 
Development and Validation of In Vitro Methods for Assessing Acute 
Systemic Toxicity.
--BG 5: Partnering with Industry to Advance Acute Toxicity Alternative 
Test Method Development, Validation, and Use.

     Plenary Session--Discussion of Conclusions and 
Recommendations from Breakout Groups 3, 4, and 5.
     Workshop Adjournment.

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 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, March 13, 2002). 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/go/167.


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    Dated: December 19, 2007.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
[FR Doc. E7-25536 Filed 1-2-08; 8:45 am]
BILLING CODE 4140-01-P