The OECD's micronucleus test guideline for single exposure to an agent and the genotox-kinetic alternative

The 'Organization for Economic Co-operation and Development (OECD) guidelines for the Testing of Chemicals' aims to identify whether a chemical is a genotoxic hazard, and these guidelines 'are periodically reviewed in the light of scientific progress, changing regulatory needs and animal welfare considerations'. OECD published a mammalian erythrocyte micronucleus test guideline for testing chemicals (1) that proposes: 'Animals are treated with the test chemical once…Samples of peripheral blood are taken at least twice (from the same group of animals), starting not earlier than 36 h after treatment, with appropriate intervals following the first sample, but not extending beyond 72 h'. This guidelines are base on the report by the Collaborative Study Group for the Micronucleus Test (CSGMT), which was based on the sampling of mice peripheral blood every 24 h We investigated the kinetics of micronucleus induction by taking samples prior to administration and every 8 or 10 h after single treatment. The comparisons suggest that 24-h sampling could cause not only an underestimation of the responses to various agents but also a misestimation of the time of maximal induction. We proposed that samples of peripheral blood must be collected at two different times during an optimal 25-h sampling range (from 25 to 50 h). Besides, we hypothesize that the time of maximal EPC-MN induction depends on the time required for the mechanisms involved in micronucleus production; and we suggest that a kinetic analysis of MN-PCE induction by several agents with well-known mechanisms of micronuclei induction would allow derivation of a specific relationship between the kinetics of MN-PCE induction and some process of DNA breaks and/or micronuclei induction.