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NICEATM is evaluating the integration of data from various sources into testing strategies that
can be used to reduce animal use to identify substances with the potential to cause allergic contact
dermatitis (ACD). One approach involves combining an assessment of physical and chemical properties
and data from an in vitro test method with use of the murine local lymph node assay (LLNA). This
approach has the potential to reduce animal use by 67% compared with use of the LLNA alone.
Background and Details on the Test Methods
Skin sensitizers are substances with the potential to cause ACD, and skin sensitization is the process
by which a sensitizer induces the development of ACD. The biochemical pathway leading to skin sensitization
includes several steps: penetration of the potential sensitizer into the skin, binding to
proteins in the skin, mobilization of immune cells in response to the sensitizer, proliferation of
cells in the lymph nodes stimulated by immune cell activity, and skin inflammation upon subsequent
exposure to the potential sensitizer.
The potential for a substance to bind with skin proteins can be assessed by evaluating
its physical and chemical properties and by testing the substance using the electrophilic
allergen screening assay (EASA). The EASA
identifies a potential sensitizer by measuring binding of a test substance to chemical probes that
contain structures commonly found in skin proteins. The developer of the EASA submitted a nomination
in 2012 requesting that NICEATM and ICCVAM evaluate
this method as a screening assay for identification of potential sensitizers.
The LLNA measures the proliferation of lymph node cells after application of a substance to the
skin of a test animal, and has been recommended by ICCVAM to identify potential sensitizers. While
updated versions of the LLNA enable substantial reductions in animal use, use of the LLNA in
combination with the EASA and evaluation of a substance’s physical and chemical structure may
enable the identification of potential sensitizers using even fewer animals.
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