National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/40500

ICCVAM Evaluations of Non-Animal Skin Sensitization Test Methods and Testing Strategies

ICCVAM is committed to advancing the state of the science for alternative test methods and testing strategies for skin sensitization, and is developing a plan of action to augment and support this goal. Activities ICCVAM is considering include organizing workshops; developing guidance documents; collaborating with international organizations that are conducting relevant validation studies or preparing relevant guidance; providing support to NICEATM's efforts in this area; and providing information about funding resources and agency priorities to test method developers. As part of this process, ICCVAM is interested in receiving information on the state of the science regarding alternative test methods and testing strategies for skin sensitization and about activities of which ICCVAM may not be aware.

ICCVAM also invites its stakeholders to consider these proposed activities and provide comment on the following:

  • The role ICCVAM should play in the development and evaluation of alternative skin sensitization test methods and testing strategies
  • The potential contributions that regulated industries or nongovernment organizations and other interested parties might make toward these efforts

ICCVAM will also request comment from ICATM partners and the OECD on these questions. ICCVAM will then consider all comments received as it develops plans to augment and support activities that will advance the state of the science for alternative skin sensitization test methods and testing strategies.

Please submit comments and information in response to this request via email to niceatm@niehs.nih.gov. With your comment, please include your name, affiliation (if applicable), mailing address, telephone, email, and sponsoring organization (if any). Responses received will be identified by name and affiliation or sponsoring organization if provided. Please do not include any proprietary, classified, confidential, or sensitive information in responses.

View comments received in response to notice

Federal Register notice: Request for Information on Alternative Skin Sensitization Test Methods and Testing Strategies and for Comment on ICCVAM's Proposed Activities (78 FR 68076, November 13, 2013)
View notice as webpage

NICEATM LLNA Database

On behalf of ICCVAM, NICEATM has conducted a number of analyses to evaluate the usefulness of the murine local lymph node assay (LLNA) to identify potential skin sensitizers. NICEATM is making this data available for reference to interested stakeholders for developing and evaluating alternative methods that replace, reduce, or refine the use of animals for skin sensitization testing.

NICEATM LLNA database

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.

Background on Skin Sensitization Test Methods

Allergic contact dermatitis (ACD) is a skin reaction characterized by localized redness, swelling, blistering, or itching after direct contact with a skin allergen. Pesticides and other marketed chemicals, including cosmetic ingredients, are routinely tested for their potential to cause ACD so that products can be appropriately labeled for safe use and handling.

Substances with the potential to cause ACD are known as skin sensitizers, and skin sensitization is the process by which a sensitizer induces the development of ACD. For substances that initiate the process through covalent binding to skin proteins, the key biological events have been fairly well characterized.  These events form the basis for an “adverse outcome pathway” (AOP) for skin sensitization. An AOP is a conceptual model that links exposure to a substance to a toxic effect by identifying the sequence of biochemical events required to produce the toxic effect (learn more about AOPs on the OECD website). The AOP for skin sensitization provides a framework for the development of alternative toxicity tests that can assess chemical effects on each biological event in the pathway and thereby provide evidence on whether a substance causes skin sensitization.

Current ICCVAM Activities

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 assays such as the electrophilic allergen screening assay (EASA) and the direct peptide reactivity assay. 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, and ICCVAM is considering that nomination in the context of ongoing international evaluations of testing approaches intended to replace the use of animals in skin sensitization testing. These include studies being conducted by the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) and by Cosmetics Europe. NICEATM and ICCVAM have provided expertise and advice to the management group conducting the EURL ECVAM study, and will have opportunities to comment on Cosmetics Europe's ongoing evaluations of alternative test methods and testing strategies.

Information about the EASA Nomination

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.