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Representatives from NICEATM (National Institute of Environmental Health Sciences) and ICCVAM participated on the management team for a validation study conducted by the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). The aim of this study was to assess an in vitro test method for evaluating human liver metabolism and toxicity. Advancing novel in vitro test methods for evaluating metabolism and toxicity is a key step in developing in vitro alternatives for in vivo toxicity studies.
The validation study assessed the potential of clinically relevant doses of pharmaceuticals to induce liver enzymes in a human liver cancer cell line (HepaRG®) and cryopreserved primary human liver cells. Liver cytochrome P450 (CYP) enzymes play a major role in biotransformation, the process that converts a substance into a chemically different substance, in humans and other animals. Biotransformation in the liver can potentially increase or decrease chemical toxicity. A stable in vitro model with functional CYP enzyme activity is important for a non-animal assessment of the contribution of biotransformation to toxicity.
The validation study management team issued a draft report on the completed study (2013) in March 2014. The team also contributed to development of the “Draft Proposal for a New Performance Based Test Guideline: Human Cytochrome P450 (CYP) n-fold Induction In Vitro Test Method,” which was made available for comment in July 2015 by the Organisation for Economic Co-operation and Development (OECD). Team members are currently revising the study report and the draft test guideline to address public comments.
Study report and draft test guideline are available on the OECD website.