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Identification of Substances That May Cause Allergic Contact Dermatitis

Substances with the potential to cause allergic contact dermatitis (ACD) are skin sensitizers; the process by which they cause ACD is skin sensitization.

Based on collaborative efforts between NTP and NICEATM, NTP immunotoxicity tests designed to evaluate dermal hypersensitivity (skin sensitization) are now conducted using a combination of in vitro test methods. Read more about NTP dermal hypersensitivity evaluations

Defined Approaches to Identify Potential Skin Sensitizers

EPA issued a draft Science Policy to reduce animal use to identify potential skin sensitizers. Read More

The biological pathway resulting in skin sensitization is well-characterized and provides a framework for the near-term development of testing approaches that eliminate the use of animals. ICCVAM and NICEATM scientists and collaborators have developed defined approaches for testing based on this pathway, using chemical property information and non-animal test data as inputs for their models. These non-animal approaches can be used to predict either outcomes for the standard animal test to identify potential skin sensitizers or human skin sensitization hazard.

Electrophilic Allergen Screening Assay (EASA)

Binding of a chemical to skin proteins is the first step in the development of ACD. The EASA is a chemical assay that measures light absorbance or a fluorescent signal in proportion to a chemical’s tendency to bind to proteins.

The EASA was nominated to ICCVAM to evaluate its usefulness in identifying potential skin sensitizers. Four ICCVAM member agencies are participating in an ongoing validation study of the EASA. Testing of 10 chemicals during 2018 showed that the method had sufficiently good reproducibility and accuracy rates to support further evaluation. In 2019, the Consumer Product Safety Commission and NIST modified the assay to a 96-well format to increase throughput and accessibility of the assay. Testing of 20 chemicals will be conducted using the 96-well assay during 2020.

ICCVAM Evaluations of the Murine Local Lymph Node Assay (LLNA)

Compared to guinea pig methods originally used to identify skin sensitizers, the LLNA:

  • Reduces the number of animals required for testing.
  • Requires less time to perform.
  • Provides dose-response information.
  • Eliminates the pain and distress associated with an allergic response in animals.

ICCVAM originally evaluated the LLNA in 1998 and recommended it as an alternative to guinea pig tests for assessing ACD hazard potential. In response to a 2007 nomination from CPSC, ICCVAM evaluated several other versions of the LLNA that reduce animal use and eliminate the need to use radioactive materials. ICCVAM also recommended the use of the LLNA for testing a wider range of chemicals and developed performance standards for the LLNA.


Data from analyses of the LLNA conducted on behalf of ICCVAM by NICEATM are available to interested stakeholders as a reference for developing and evaluating alternative approaches to testing and assessment that replace, reduce, or refine the use of animals for identification of potential skin sensitizers.


Database users please note:

  • The Excel spreadsheet contains three pages: (1) data, (2) references, and (3) abbreviations.
  • The database includes data published through 2010.
  • These data have been extracted from published and unpublished data sources with permission. Users of this database should consult the original data source for questions regarding data quality and/or authenticity.