Division 3.2.2.2 Genotoxicity studies including mutagenicity

To identify active substances and, if appropriate, their metabolites and degradation products with mutagenic and genotoxic properties, a selected combination of different genotoxicity tests must be carried out. If appropriate the tests shall be performed without and with mammalian metabolic activation and the compatibility of the test material with the test system shall be taken into account.

The core set comprises the following tests:

1. (1)

   induction of gene mutations in bacteria and/or in mammalian cells (preferably the mouse lymphoma tk assay);

2. (2)

   induction of chromosomal aberrations in mammalian cells; and

3. (3)

   in vivo test in mammalian species.

Additional tests may be needed depending on the outcome of the above mentioned tests and taking into consideration the whole toxicity profile of the substance, as well as its intended use.

Protocols should be in line with OECD Guideline 471 (Salmonella typhimurium Reverse Mutation Test), 472 (Escherichia coli Reverse Mutation Test), 473 (in vitro Mammalian Chromosomal Aberration Test), 474 (Mammalian Erythrocyte Micronucleus Test), 475 (Mammalian Bone Marrow Chromosomal Aberration Test), 476 (in vitro Mammalian Cell Gene Mutation Test) or 482 (Unscheduled DNA Synthesis in Mammalian Cells in vitro), as well as other relevant OECD Guidelines for in vitro and in vivo assays.