[Federal Register: March 25, 2008 (Volume 73, Number 58)]
[Notices]
[Page 15757-15758]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr25mr08-54]
=======================================================================
-----------------------------------------------------------------------
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: In Vitro
Cytotoxicity Test Methods for Estimating Starting Doses for Acute Oral
Systemic Toxicity Tests and the Final Background Review Document for In
Vitro Cytotoxicity Test Methods for Estimating Acute Oral Systemic
Toxicity; 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 Document.
-----------------------------------------------------------------------
SUMMARY: NICEATM announces availability of the ICCVAM Test Method
Evaluation Report: In Vitro Cytotoxicity Test Methods for Estimating
Starting Doses for Acute Oral Systemic Toxicity Tests (NIH Publication
07-4519). The report describes two in vitro basal cytotoxicity neutral
red uptake (NRU) test methods that can be used for estimating starting
doses for acute oral toxicity tests. The report includes ICCVAM's (a)
final test method recommendations on the use of these two test methods,
(b) recommended test method protocols for future use, (c)
recommendations for future studies to further characterize the
usefulness and limitations of in vitro methods for assessing acute
systemic toxicity, and (d) recommended performance standards for tests
with similar scientific principles and that measure or predict acute
oral systemic toxicity. The report recommends the use of these methods
in a weight-of-evidence approach to determine starting doses for acute
oral systemic toxicity tests with rodents. The report also recommends
that these in vitro test methods be considered before using animals for
acute oral systemic toxicity testing and used when determined
appropriate.
NICEATM also announces the availability of the final Background
Review Document: In Vitro Cytotoxicity Test Methods for Estimating
Acute Oral Systemic Toxicity (BRD) (NIH Publication 07-4518). The BRD
provides data and analyses from a collaborative international
validation study organized by NICEATM and the European Centre for the
Validation of Alternative Methods (ECVAM) to evaluate the usefulness
and limitations of two in vitro basal cytotoxicity NRU test methods
using either BALB/c 3T3 mouse fibroblasts (3T3) or primary human
epidermal keratinocytes (NHK) for estimating acute oral rodent
toxicity.
Electronic copies of the ICCVAM Test Method Evaluation Report and
the BRD are available from the ICCVAM/NICEATM 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 BRD 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, NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC
27709, (phone) 919-541-2384, (fax) 919-541-0947, (e-mail)
niceatm@niehs.nih.gov. Courier address: NICEATM, NIEHS, 79 T.W.
Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC
27709.
SUPPLEMENTARY INFORMATION:
Background
In 2002, NICEATM and ECVAM initiated a collaborative,
international, multi-laboratory validation study to independently
evaluate the usefulness of the 3T3 and NHK NRU basal cytotoxicity test
methods for estimating acute oral rodent toxicity and for estimating
starting doses for in vivo rodent acute oral toxicity tests. The 3T3
and NHK NRU test methods were evaluated with 72 reference substances.
Once the study was completed in January 2005, NICEATM prepared a draft
BRD that contained comprehensive summaries of the data generated in the
validation study, analyses of the relevance and reliability of the two
test methods, and simulation analyses of the refinement (i.e., to
lessen or avoid pain and distress) and reduction in animal use that
might occur if these tests were used as adjuncts to two acute oral
toxicity test methods (i.e., the Up-and-Down Procedure and the Acute
Toxic Class method). The draft BRD was released for public comment on
March 21, 2006 (Federal Register, Vol. 71, No. 54, pp. 14229-14231).
On May 23, 2006, NICEATM, on behalf of ICCVAM, convened an
independent, scientific peer review panel meeting to review the draft
BRD and evaluate the validation status of the 3T3 and NHK NRU test
methods for determining starting doses for in vivo acute oral systemic
toxicity tests. The peer review panel's report was released in July
2006 (Federal Register, Vol. 71, No. 132, pp. 39122-39123). At a public
teleconference meeting on August 3, 2006 (Federal Register, Vol. 71,
No. 132, pp. 39121-39122), the Scientific Advisory Committee on
Alternative Toxicological Methods (SACATM) reviewed and endorsed the
conclusions of the peer review panel (minutes from the teleconference
are available at http://ntp.niehs.nih.gov/files/
SACATMAug06MinutesVF081506.pdf).
ICCVAM considered the peer panel report, public comments, SACATM
comments, and the draft BRD in finalizing its recommendations on the
use of these two in vitro basal cytotoxicity test methods for
estimating starting doses for acute oral systemic toxicity tests. The
ICCVAM Test Method Evaluation Report includes the ICCVAM
[[Page 15758]]
recommendations on the use of the two in vitro NRU test methods, as
well as recommended test method protocols, recommendations for future
studies to further characterize the usefulness and limitations of in
vitro methods for assessing acute systemic toxicity, recommended
performance standards for tests with similar scientific principles and
that measure or predict acute oral systemic toxicity, the peer panel
report and Federal Register notices. The final BRD, which provides the
supporting documentation for this report, is available as a separate
document. The ICCVAM Test Method Evaluation Report and the supporting
final BRD 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: March 14, 2008.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences
and National Toxicology Program.
[FR Doc. E8-5936 Filed 3-24-08; 8:45 am]
BILLING CODE 4140-01-P