National Toxicology Program

National Toxicology Program

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)
View Table of Contents as webpage

At the request of the U.S. Environmental Protection Agency, ICCVAM established performance standards for in vitro test methods for skin corrosion. These performance standards were based on ICCVAM evaluations of in vitro methods to identify potential dermal corrosives; they can be used to evaluate the usefulness and limitations of other test methods that are based on similar scientific principles that measure or predict the same biological or toxic effect.

Subsequently, ICCVAM and NICEATM drafted proposed updates to Organisation for Economic Co-operation and Development (OECD) test guidelines for in vitro methods for identifying skin corrosives (OECD Test Guidelines 430 and 431). These updates, which were based on the ICCVAM performance standards, were adopted by OECD in 2013.

In 2011, the U.S. Department of Transportation’s (DOT) Pipeline and Hazardous Materials Safety Administration announced revisions to its hazardous materials regulations. These revisions included acceptance of the in vitro methods described in OECD Test Guidelines 430 and 431. Substances with negative tests using these methods can be assigned to packing groups without further testing, reducing animal use for this purpose.
View final rule (January 2011)

Details of the Performance Standards

The three elements of performance standards are:

  • Essential test method components (a list of specifically required structural, functional, and procedural elements derived from mechanistically and functionally similar validated test methods)
  • 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 for in vitro skin corrosion test methods describe standards that should be met by in vitro corrosivity test methods utilizing membrane barrier test systems, cultured human skin model systems, and the rat skin transcutaneous electrical resistance test method.

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

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 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.

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