National Toxicology Program

At the request of the U.S. EPA, ICCVAM established performance standards for in vitro test methods for skin corrosion. These performance standards were based on four in vitro test methods evaluated by ICCVAM for the identification of substances with the potential to cause skin corrosion. These perforrnance standards can be used to evaluate the reliability and accuracy of other test methods that are based on similar scientific principles and that measure or predict the same biological or toxic effect.

Performance Standards for In Vitro Test Methods for Skin Corrosion

Recommended Performance Standards for In Vitro Test Methods for Skin Corrosion: Prepared by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)

NIH Publication Number 04-4510 (May 2004) [PDF]

The three elements of performance standards are:

• Essential test method components (structural, functional, and procedural elements of a validated test method to which a proposed mechanistically and functionally similar test methods should adhere)
• A minimum list of reference chemicals to be used to assess the accuracy and reliability of the proposed test method
• The accuracy and reliability values that should be achieved by the proposed test method when evaluated using the minimum list of reference chemicals

The ICCVAM performance standards document describes standards that should be met by in vitro corrosivity test methods that utilize membrane barrier test systems, cultured human skin model systems, or the rat skin TER test method.

The performance standards for human skin models require a minimum of 24 reference chemicals (12 noncorrosives and 12 corrosives). These chemicals represent a distribution of the 60 chemicals used in the European Centre for the Validation of Alternative Methods (ECVAM) validation study of EPISKIN™, as well as the range of corrosivity responses obtained for the in vivo rabbit skin reference test method. Included in this list are five organic bases, four inorganic acids, three inorganic bases, three organic acids, three electrophiles, three phenols, two neutral organics, and one surfactant.

Transcutaneous Electrical Resistance methods for skin corrosivity also require a minimum of 24 reference chemicals (12 noncorrosives and 12 corrosives). These chemicals are representative of the 60 chemicals used in the ECVAM validation study of the rat skin TER assay and the range of corrosivity responses obtained for the in vivo rabbit skin reference test method. Included in this list are five organic bases, four organic acids, four inorganic acids, three electrophiles, three neutral organics, two inorganic bases, two phenols, and one surfactant.

Membrane barrier tests for skin corrosivity, including Corrositex®, require a minimum of 40 reference chemicals representing the chemical classes of interest and the range of corrosivity responses (i.e., noncorrosive chemicals, corrosive chemicals from U.S. Department of Transportation [DOT] Packing Groups I, II, and III, and chemicals from U.N. GHS Skin Corrosion Categories 1, 2, and 3) obtained for the in vivo reference test method. These 40 chemicals consist of eight acid derivatives, eight inorganic acids, eight organic acids, seven organic bases, two acid esters, four inorganic bases, one electrophile, one quaternary ammonium, and one surfactant. Note that while more reference chemicals are required in the performance standards for membrane barrier tests, these are the only in vitro test methods that can subcategorize the corrosivity hazards into recognized U.S. DOT and U.N. hazard classifications.