[Federal Register Volume 75, Number 180 (Friday, September 17, 2010)]
[Notices]
[Pages 57027-57029]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-23262]
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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); Availability
of Interagency Coordinating Committee on the Validation of Alternative
Methods (ICCVAM) Test Method Evaluation Reports: In Vitro Ocular Safety
Testing Methods and Strategies, and Routine Use of Topical Anesthetics,
Systemic Analgesics, and Humane Endpoints for Ocular Safety Testing;
Notice of Transmittal to Federal Agencies
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH).
ACTION: Availability of ICCVAM Test Method Evaluation Reports (TMERs);
Notice of Transmittal.
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SUMMARY: NICEATM announces availability of ICCVAM TMERs that provide
recommendations regarding proposed in vitro ocular safety testing
methods, testing strategies, and the routine use of anesthetics,
analgesics, and humane endpoints for ocular safety testing to avoid or
minimize any pain and distress. The reports and recommendations have
been transmitted to Federal agencies for their review and response to
ICCVAM in accordance with the ICCVAM Authorization Act of 2000. In the
first report, ICCVAM recommends pain management procedures that should
always be used to avoid or minimize pain and distress when it is
determined necessary to conduct the
[[Page 57028]]
rabbit eye test for regulatory safety purposes. In the second report,
ICCVAM recommends that the Cytosensor microphysiometer (CM) test method
can be used as a screening test to identify some types of substances
that may cause permanent or severe eye injuries. ICCVAM also recommends
that the CM test method can be used to determine if some types of
substances will not cause sufficient injury to require hazard labeling
for eye irritation. ICCVAM evaluated four other in vitro test methods
for their usefulness and limitations for identifying substances with
the potential to cause reversible and nonsevere ocular injuries, but
concluded that the performance of these methods must be improved before
they can be used for regulatory safety testing to classify such
substances. The report includes ICCVAM recommendations for future
studies that could potentially improve these test methods. In the third
report, ICCVAM recommends further studies to characterize the
usefulness and limitations of a non-animal in vitro testing strategy
that uses three in vitro test methods. In the fourth report, ICCVAM
recommends that a proposed low volume rabbit eye test (LVET) should not
be used for regulatory testing due to performance issues when compared
to the current standard rabbit eye test.
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)
[email protected]. Courier address: NICEATM, NIEHS, Room 2034, 530
Davis Drive, Morrisville, NC 27560.
SUPPLEMENTARY INFORMATION:
Background
In October 2003, the U.S. Environmental Protection Agency (EPA)
requested ICCVAM to: (1) Evaluate the current validation status of the
bovine corneal opacity and permeability (BCOP), hen's egg test-
chorioallantoic membrane (HET-CAM), isolated chicken eye (ICE), and
isolated rabbit eye (IRE) test methods; (2) identify in vivo ocular
toxicity reference data to support the validation of in vitro test
methods; (3) explore ways of alleviating pain and suffering from
current in vivo ocular safety testing; and (4) review the state of the
science and the availability of in vitro test methods for assessing
mild or moderate ocular irritants. The highest priority activity, an
evaluation of the BCOP, HET-CAM, ICE, and IRE test methods for their
ability to identify potential ocular corrosives, was completed in 2006
(NIH Publication No. 07-4517; available at http://iccvam.niehs.nih.gov/methods/ocutox/ivocutox/ocu_tmer.htm). ICCVAM recently completed
additional test method evaluations relevant to the original EPA
nomination and a subsequent EPA request for ICCVAM to evaluate a
proposed in vitro testing strategy for identifying the ocular hazard
potential of antimicrobial cleaning products (AMCPs).
NICEATM and ICCVAM compiled comprehensive draft background review
documents (BRDs) and released them for public comment in March 2009 (74
FR 14556). ICCVAM convened a public panel meeting on May 19-21, 2009,
to review the draft documents and assess whether the information they
contained supported draft ICCVAM test method recommendations for test
method uses and limitations, updated standardized test method
protocols, and proposed future studies. The panel considered public
comments made at the meeting as well as public comments submitted in
advance of the meeting before concluding its deliberations. The panel's
report was made available in July 2009 (74 FR 33444) for public
comment. The draft ICCVAM BRDs, draft ICCVAM test method
recommendations, the panel's report, and all public comments were made
available to ICCVAM's Scientific Advisory Committee on Alternative
Toxicological Methods (SACATM) for comment at its meeting on June 25-
26, 2009 (74 FR 19562).
After considering the conclusions and recommendations of the panel,
comments from SACATM, and public comments, ICCVAM forwarded final test
method recommendations to U.S. Federal agencies for their
consideration. Agency responses to the ICCVAM test method
recommendations will be made available on the NICEATM-ICCVAM Web site
(http://www.iccvam.niehs.nih.gov) as they are received.
The ICCVAM TMER, Recommendations for Routine Use of Topical
Anesthetics, Systemic Analgesics, and Humane Endpoints to Avoid or
Minimize Pain and Distress in Ocular Safety Testing (NIH Publication
No. 10-7514) provides ICCVAM's evaluation and recommendations for the
routine use of topical anesthetics, systemic analgesics, and humane
endpoints to avoid or minimize pain and distress in ocular safety
testing. ICCVAM concludes that balanced preemptive pain management
procedures should always be provided when it is determined necessary to
conduct the rabbit eye test for regulatory safety assessments. ICCVAM
also identifies clinical signs and ocular lesions that are considered
predictive of an ocular corrosive or severe irritant response and,
therefore, can be routinely used as humane endpoints to end studies
early when deemed appropriate. The report also includes a test method
protocol that incorporates the ICCVAM-recommended procedures, the final
BRD, and the panel's peer review report.
The ICCVAM TMER, Current Validation Status of In Vitro Test Methods
Proposed for Identifying Eye Injury Hazard Potential of Chemicals and
Products (NIH Publication No. 10-7553) provides ICCVAM's updated
evaluation and recommendations for the use of five in vitro ocular test
methods (i.e., BCOP, CM, HET-CAM, ICE, and IRE) for their ability to
identify nonsevere ocular irritants and substances not labeled as
irritants. ICCVAM concludes that the CM test method can be used as a
screening test to identify test substances within a defined limited
applicability domain that may cause permanent or severe eye injuries.
ICCVAM also recommends that the CM can be used to determine if
substances within an even more restricted applicability domain will not
cause sufficient injury to require hazard labeling for eye irritation.
The performance of the remaining four in vitro test methods must be
improved before they can be used in regulatory safety testing for
classifying substances not labeled as irritants. None of these in vitro
test methods were considered adequately predictive of all ocular hazard
categories to support their use as a complete replacement for the
current standard rabbit eye test. This report also includes updated
ICCVAM-recommended BCOP, CM, HET-CAM, ICE, and IRE test method
protocols, final BRDs for the BCOP, CM, HET-CAM, and ICE test methods,
and the panel's peer review report.
ICCVAM also discovered during these evaluations that an estimated
30% of chemicals identified as eye hazards by current U.S. regulations
will not be labeled as eye hazards by the United Nations Globally
Harmonized System for Classification and Labelling of Chemicals (GHS),
which some Federal agencies are or will be considering for
implementation. The reduced hazard labeling that will result from
implementing the GHS was based on analyzing actual testing data for
over 250 chemicals. Of concern is that over 50% of the chemicals that
will no longer be labeled using GHS criteria produced eye injuries
expected to interfere with normal vision. Accordingly, the report
[[Page 57029]]
includes an optional GHS hazard category that could be used to provide
at least equivalent hazard labeling as current U.S. regulations in
order to support continued protection of consumers and workers.
The ICCVAM TMER, Current Validation Status of a Proposed In Vitro
Testing Strategy for U.S. Environmental Protection Agency Ocular Hazard
Classification and Labeling of Antimicrobial Cleaning Products (NIH
Publication No. 10-7513) provides ICCVAM's evaluation and
recommendations regarding the use of a proposed in vitro testing
strategy to classify and label AMCPs for eye irritation. ICCVAM
concludes that the data are insufficient to adequately demonstrate that
the proposed in vitro testing strategy can classify test substances to
all four EPA ocular hazard categories. ICCVAM recommends further
studies to characterize the usefulness and limitations of the non-
animal in vitro testing strategy that uses the three in vitro test
methods. This report also includes updated ICCVAM-recommended BCOP, CM,
and EpiOcular \TM\ test method protocols, the final summary review
document (SRD), and the panel's peer review report.
The ICCVAM TMER, Recommendation to Discontinue Use of the Low
Volume Eye Test for Ocular Safety Testing (NIH Publication No. 10-7515)
provides ICCVAM's evaluation and recommendations on the usefulness of
the LVET as an in vivo reference test method. ICCVAM concludes that the
proposed LVET should not be used for regulatory safety testing due to
performance issues.
Background Information on ICCVAM, NICEATM, and SACATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that require, use, or
generate toxicological and safety testing information for chemicals,
products, and other substances. ICCVAM conducts technical evaluations
of new, revised, and alternative methods with regulatory applicability,
and promotes the scientific validation and regulatory acceptance of
toxicological and safety testing methods that more accurately assess
the safety and health hazards of chemicals and products while reducing,
refining (decreasing or eliminating pain and distress), or replacing
animal use. The ICCVAM Authorization Act of 2000 (42 U.S.C. 285l-2,
285l-5 [2000], available at http://iccvam.niehs.nih.gov/docs/about_docs/PL106545.pdf) established ICCVAM as a permanent interagency
committee of the NIEHS under NICEATM.
NICEATM administers ICCVAM, provides scientific and operational
support for ICCVAM-related activities, and coordinates international
validation studies of new and improved test methods. NICEATM and ICCVAM
work collaboratively to evaluate new and improved test methods
applicable to the needs of U.S. Federal agencies. NICEATM and ICCVAM
welcome the public nomination of new, revised, and alternative test
methods for validation studies as well as technical evaluations.
Additional information about NICEATM and ICCVAM can be found on the
NICEATM-ICCVAM Web site (http://www.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/go/167.
References
ICCVAM. 2006. ICCVAM Test Method Evaluation Report: In Vitro Ocular
Toxicity Test Methods for Identifying Severe Irritants and Corrosives.
NIH Publication No. 07-4517. Research Triangle Park, NC: NIEHS.
Available: http://iccvam.niehs.nih.gov/methods/ocutox/ivocutox/ocu_tmer.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Recommendations for
Routine Use of Topical Anesthetics, Systemic Analgesics, and Humane
Endpoints to Avoid or Minimize Pain and Distress in Ocular Safety
Testing. NIH Publication No. 10-7514. Research Triangle Park, NC:
NIEHS. Available: http://iccvam.niehs.nih.gov/methods/ocutox/OcuAnest-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Current Validation
Status of In Vitro Test Methods Proposed for Identifying Eye Injury
Hazard Potential of Chemicals and Products. NIH Publication No. 10-
7553. Research Triangle Park, NC: NIEHS. Available: http://iccvam.niehs.nih.gov/methods/ocutox/MildMod-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Current Validation
Status of a Proposed In Vitro Testing Strategy for U.S. Environmental
Protection Agency Ocular Hazard Classification and Labeling of
Antimicrobial Cleaning Products. NIH Publication No. 10-7513. Research
Triangle Park, NC: NIEHS. Available: http://iccvam.niehs.nih.gov/methods/ocutox/AMCP-TMER.htm.
ICCVAM. 2010. ICCVAM Test Method Evaluation Report: Recommendation to
Discontinue Use of The Low Volume Eye Test for Ocular Safety Testing.
NIH Publication No. 10-7515. Research Triangle Park, NC: NIEHS.
Available: http://iccvam.niehs.nih.gov/methods/ocutox/LVET.htm.
Dated: September 10, 2010.
John R. Bucher,
Associate Director, National Toxicology Program.
[FR Doc. 2010-23262 Filed 9-16-10; 8:45 am]
BILLING CODE 4140-01-P