Chromosome aberration testing in genetic toxicology-past, present and future

In vitro metaphase tests for chromosomal aberrations (CA) have undergone considerable evolutionary changes over the last 20 yr. Treatment and sampling times have been a particular focus of attention as we have tried to develop protocols that detect weak genotoxins. Different approaches evolved in different parts of the world and led to a need to harmonise. At the same time, we have increasingly challenged the conditions in which clastogens produce positive responses, and several situations have been described in which clastogenic responses would be considered not to be biologically relevant. Now there is a strong case to replace the conventional metaphase analysis test with an in vitro micronucleus test. The time is therefore right to carefully consider whether the type of damage scored in CA tests is relevant for human health.