The purpose of this type of study is to determine whether the test item causes genotoxic effects resulting in the formation of micronuclei containing lagging chromosome fragments or whole chromosomes, in the erythrocytes of treated animals.
The mammalian in vivo micronucleus test is used for the detection of cytogenetic damage induced by the test item to the chromosomes or the mitotic apparatus of erythroblasts by analysis of erythrocytes sampled from rodent blood. When a bone marrow erythroblast develops into a polychromatic erythrocyte, the main nucleus is extruded and any micronucleus that has been formed remains in the otherwise anucleated cytoplasm. Visualization of micronuclei is facilitated in these cells because they lack the main nucleus. An increase in the frequency of micronucleated polychromatic erythrocytes in treated animals is an indication of induced chromosome damage.
Mice or rats are generally used.
Animals should be assigned in vehicle and positive control groups and in three dose groups.
Single administration of the test item is performed.
Micronuclei are analyzed in the CD71-positive immature erythrocyte with flow cytometric method. Frequency of micronucleated reticulocytes in relation to total number of reticulocytes (%MN-RET) is determined.