In Vitro Test Methods for Dermal Corrosivity Testing
Dermal corrosives are substances that can cause burns or permanent scarring to the skin. This page describes ICCVAM evaluations of in vitro methods to identify dermal corrosives.
EPISKIN, EpiDerm, and Rat Skin Transcutaneous Electrical Resistance Assay
Following a comprehensive review in 2002, ICCVAM recommended three in vitro methods–EPISKIN™, EpiDerm™, and the rat skin transcutaneous electrical resistance assay–that could be used for classification and labeling of potential dermal corrosives without further testing.
ICCVAM Test Method Evaluation Report
ICCVAM Evaluation of EPISKIN™, EpiDerm™ (EPI-200), and the Rat Skin Transcutaneous Electrical Resistance (TER) Assay: In Vitro Test Methods for Assessing the Dermal Corrosivity Potential of Chemicals
(NIH Publication No. 02-4502, June 2002)
Background and Evaluation
Regulatory agencies require testing to identify dermal corrosives. Results of these tests are used to label substances so that users can take appropriate safety precautions; to determine appropriate packaging requirements; and to develop safe handling procedures for chemical spills.
The European Centre for the Evaluation of Alternative Methods (ECVAM, now known as EURL ECVAM) conducted validation studies of the suitability of three in vitro methods for identification of substances with the potential to cause human skin corrosion: EpiDerm™, EPISKIN™, and the rat skin transcutaneous electrical resistance assay. ECVAM concluded that these methods were able to distinguish between corrosive and noncorrosive substances for all of the classes considered. ICCVAM based its recommendations on these methods on the ECVAM studies and other available data.
These in vitro assays are accepted internationally via test guidelines issued by the Organisation for International Co-operation and Development (OECD). Human skin model test methods such as EPISKIN and EpiDerm are described in OECD Test Guideline 431. The rat skin transcutaneous electrical resistance assay is described in OECD Test Guideline 430.
ICCVAM Background Review Document and Related References
- ICCVAM Background Review Document: EPISKIN™, EpiDerm™, and Rat Skin Transcutaneous Electrical Resistance (TER): In Vitro Test Methods for Assessing the Dermal Corrosivity Potential of Chemicals (August 2001)
- European Centre for the Validation of Alternative Methods (ECVAM): Statement on the Scientific Validity of the EPISKIN™ Test (March 1998)
- INVITTOX Protocol for the EPISKIN™ Test (updated October 2002)
Performance Standards for In Vitro Test Methods for Skin Corrosion
In response to an EPA request, ICCVAM established performance standards for in vitro test methods for skin corrosion. These performance standards were based on the ICCVAM evaluations described above of in vitro methods to identify potential dermal corrosives. The resulting document (published in 2004) establishes a basis to evaluate the usefulness and limitations of other test methods that are based on similar scientific principles.
After the performance standards were published, ICCVAM and NICEATM drafted proposed updates to OECD test guidelines. These proposed updates included 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.
- The DOT Pipeline and Hazardous Materials Safety Administration revised its hazardous materials regulations to include acceptance of the in vitro methods described in 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.
- Test Guideline 431 was updated in 2013, 2016, and 2019 to include additional test methods using reconstructed human epidermis models, including methods validated based on the performance standards.
- Test Guideline 431 was also updated in 2015 to introduce the possibility to use the methods to support the subcategorization of corrosive chemicals.
Corrositex Test Method for Dermal Corrosivity Testing
ICCVAM convened an independent peer review panel meeting in 1999 to evaluate Corrositex® for the identification of potential skin corrosives. This assay tests if a substance can pass through a biobarrier by diffusion, erosion, or destruction.
The panel concluded that:
- Corrositex is useful for certain testing circumstances, such as testing performed to comply with DOT regulations.
- Corrositex can serve as a stand-alone test for evaluating the corrosivity or noncorrosivity of acids, bases, and acid derivatives and can replace the use of animals.
Corrositex is accepted as an alternative to a procedure specified in the DOT Hazardous Materials Regulations (DOT-SP 10904) for packing group classification of corrosive materials.
Corrositex®: An In Vitro Test Method for Assessing Dermal Corrosivity Potential of Chemicals
The Results of an Independent Peer Review Evaluation Coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
(NIH Publication No. 99-4495, June 1999)
In vitro membrane barrier methods such as Corrositex are accepted internationally via OECD Test Guideline 435. Read about this test guideline and view other related documents and sites below:
- Organisation for Economic Co-operation and Development (OECD) Test No. 435: In Vitro Membrane Barrier Test Method for Skin Corrosion
- InVitro International
- Sample Protocol: Corrositex® – A Validated and Accepted Dermal Corrosion Test Method for Classifying Substances According to the UN Packing Groups (October 2003)
ICCVAM Agency Responses to Panel Recommendations
Recommendations were originally communicated to Federal agencies in letters from NIEHS Director Dr. Kenneth Olden to the agency heads. Links to the responses from agency officials can be found below:
- Agency for Toxic Substances and Disease Registry
- Response from Henry Falk, M.D., M.P.H., Assistant Administrator (received November 29, 1999)
- Department of Defense
- Response from Robert E. Foster, Director, BioSystems (received July 14, 1999)
- Environmental Protection Agency
- Response from Steven Galson, M.D., M.P.H., Director, Office of Science Coordination and Policy (received January 3, 2000)
- National Institute for Occupational Safety and Health
- Response from Linda Rosenstock, M.D., M.P.H., Director (received December 13, 1999)