Genetic toxicity refers to the ability of substances or physical agents to damage the DNA and/or chromosomes of cells. Such damage can lead to mutations that increase the likelihood of certain diseases, such as cancer and birth defects.
The U.S. Environmental Protection Agency, the U.S. Food and Drug Administration, and the U.S. Consumer Product Safety Commission have testing requirements and guidelines in place for assessing the genetic toxicity of regulated products. ICCVAM member agency scientists review and comment on proposed validation studies, provide recommendations on test method nominations and submissions for alternative test methods, and evaluate test guidelines and relevant activities proposed to the Organisation for Economic Co-operation and Development (OECD).
The in vitro micronucleus test measures a substance’s potential for causing damage to chromosomes. Cultured human or rodent cells are treated and then examined for the presence of chromosome fragments known as micronuclei. The test is intended to reduce the number of animals used to identify substances that can lead to cancer and other adverse health effects.
ICCVAM provided comments on cytotoxicity evaluation procedures and study design for a draft OECD test guideline for the in vitro micronucleus test, and subsequently recommended approval of the test guideline based on the results of cytotoxicity study data provided by European Union and U.S. laboratories. Test Guideline 487 for the in vitro micronucleus test was formally adopted by OECD in 2010, and an updated version was adopted in 2014.
The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) included the method described in Test Guideline 487 in their Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (Guideline S2[R1]). ICH safety guidelines are internationally agreed upon standards for safety testing. Guideline S2(R1) is intended to apply to products being developed as human pharmaceuticals and is recommended for adoption to the regulatory bodies of the European Union, Japan, and USA.
NICEATM and ICCVAM, along with the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM, formerly ECVAM), participated in a validation study of the in vivo rodent comet assay sponsored by the Japanese Center for the Validation of Alternative Methods (JaCVAM). The comet assay test method is a potential alternative for the in vivo rat hepatocyte unscheduled DNA synthesis assay. OECD Test Guideline 489 for the in vivo comet assay was adopted in 2014.
NICEATM and ICCVAM are collaborating with EURL ECVAM in the assessment of carcinogenic xenobiotics using the in vitro cell transformation assay. An OECD test guideline for the in vivo cell transformation assay is currently under development; a draft test guideline was made available in February 2013 on the OECD website.