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In January 2008, NICEATM received a submission, sponsored by the U.S. Environmental Protection
Agency (EPA), of a non-animal approach to assess the eye irritation
potential of antimicrobial cleaning products. This proposed testing strategy will utilize the
bovine corneal opacity and permeability (BCOP), the Cytosensor Microphysiometer, and the EpiOcular
in vitro test methods to determine the EPA toxicity category and labeling requirements for these substances.
NICEATM and ICCVAM evaluated of the submission and developed draft recommendations, which were reviewed in May 2009 by an independent
scientific peer review panel.
In November 2006, NICEATM published recommendations (see below) on the use of four in vitro methods for identifying
ocular corrosives and severe irritants:
- The BCOP test method
- The isolated chicken eye (ICE) test method
- The isolated rabbit eye (IRE) test method
- The hen's egg test - chorioallantoic membrane (HET-CAM) test method
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 nonirritants. NICEATM and
ICCVAM prepared draft BRDs assessing the current validation status of the four test methods
for their ability to identify moderate and mild irritants and nonirritants, and draft recommendations
on their use for this purpose. The draft documents were reviewed in May 2009 by an independent
scientific peer review panel.
At a May 2005 symposium entitled
Minimizing Pain and Distress in Ocular Toxicity Testing the participants recommended that
ICCVAM consider the use of anesthetics, analgesics, and humane endpoints for in vivo ocular toxicity testing to
minimize potential animal pain and distress. NICEATM and
ICCVAM requested data and compiled available information on using anesthetics and/or analgesics when conducting in vivo
eye irritation tests in rabbits. They then prepared a draft background review document and recommendations on
the use of topical anesthetics, systemic analgesics, and earlier humane endpoints to avoid or minimize pain and distress in ocular toxicity testing. The draft documents were reviewed in May 2009 by an independent
scientific peer review panel.
In October 2007, ICCVAM forwarded its first recommendations for the use of in vitro methods for ocular safety testing to Federal agencies.
ICCVAM recommended that the BCOP test method and the ICE test method
can be used in a tiered testing strategy, as part of a weight-of-evidence approach to identify ocular corrosives and severe irritants, with specific limitations
for certain chemical classes and/or physical properties. Substances
that test positive in these assays can be classified as ocular corrosives or severe irritants without further testing in animals. The report also recommends
that these in vitro test methods should be considered before using animals for ocular testing and used when determined appropriate. The ICCVAM recommendations were accepted by the Federal agencies,
and the two in vitro test methods may now be used
instead of conventional tests for certain regulatory testing purposes. The use of these two alternative
test methods will likely reduce the use of live animals for eye safety testing by 10 percent or more. More
importantly, the use of these tests will eliminate eye safety testing in animals of most substances likely to
cause the most severe pain and discomfort. The OECD formally adopted methods describing this use of BCOP and ICE test methods as TG 437
and TG 438, respectively, on September 7, 2009, permitting the use of these test methods internationally
to identify ocular corrosives and severe irritants without the use of animals.
ICCVAM also evaluated the IRE test method and the HET-CAM test method for this purpose. Before these two methods
can be recommended for use as screening tests for the identification of ocular corrosives and severe
irritants, the protocol and decision criteria for the identification of ocular corrosives and severe
irritants need to be optimized and undergo further validation.
Two Scientific Symposia on ocular toxicity topics were held in May 2005. Both symposia were sponsored by ICCVAM, NICEATM, the European Centre for the Validation
of Alternative Methods (ECVAM), and the European Cosmetic, Toiletry and Perfumery Association, and were organized by ICCVAM, NICEATM and ECVAM.
Symposium I: Mechanisms of Chemically-Induced Ocular Injury and
Recovery identified research needed to address current knowledge
gaps and to advance the development and validation of ocular toxicity
test methods for regulatory testing that provide for protection of
human health while reducing, refining (less pain and distress), and/or
replacing the use of animals. The participants in Symposium I made the following recommendations:
- Data collected from objective, quantitative endpoints and biomarkers should be used to assess the severity of
chemically-induced ocular injuries in animal safety studies and human accidental exposures.
- The routine collection of this data can be expected to:
- Provide insights into chemical-specific mechanisms of ocular injury and recovery
- Support the development and validation of more predictive mechanism-based in vitro test models
- Improve the accuracy and reliability of ocular hazard assessments
- Aid in identifying predictive, mechanism-based earlier humane endpoints
Symposium II:
Minimizing Pain and Distress in Ocular Toxicity Testing reviewed current understanding of the sources and mechanisms
of pain and distress in ocular toxicity testing; identified current best practices for preventing, recognizing,
and alleviating ocular pain and distress; and identified additional research, development, and validation
studies necessary to support scientifically valid ocular toxicity
testing procedures that avoid pain and distress. The participants in Symposium II made the following recommendations:
- Pre-treatment with topical or general anaesthesia should be used routinely to avoid pain from topical application
of test substances
- Systemic analgesics should be administered prior to test article application and continued until injuries resolve
or the study is terminated
- Ocular injuries predictive of severe or irreversible ocular damage should be used as earlier humane endpoints
- Objective, quantitative measurements should be collected during ocular studies to assist in identifying earlier,
more humane endpoints. Data from these measurements are also critical to the development and validation of more predictive
in vitro methods.
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