Division Circumstances in which required

The following in vitro mutagenicity tests shall be performed: bacterial assay for gene mutation, combined test for structural and numerical chromosome aberrations in mammalian cells and test for gene mutation in mammalian cells.

However, if gene mutation and clastogenicity/aneuploidy are detected in a battery of tests consisting of Ames and in vitro micronucleus (IVM), no further in vitro testing needs to be conducted.

If there are indications of micronucleus formation in an in vitro micronucleus assay further testing with appropriate staining procedures shall be conducted to clarify if there is an aneugenic or clastogenic response. Further investigation of the aneugenic response may be considered to determine whether there is sufficient evidence for a threshold mechanism and threshold concentration for the aneugenic response (particularly for non-disjunction).

Active substances which display highly bacteriostatic properties as demonstrated in a range finding test shall be tested in two different in vitro mammalian cell tests for gene mutation. Non performance of the Ames test shall be justified.

For active substances bearing structural alerts that have given negative results in the standard test battery, additional testing may be required if the standard tests have not been optimised for these alerts. The choice of additional study or study plan modifications depends on the chemical nature, the known reactivity and the metabolism data on the structurally alerting active substance.