Stochastic modeling in toxicokinetics. Application to the in vivo micronucleus assay (Q5934205)

A stochastic model for the in vivo micronucleus assay is presented. This model describes the kinetics of the rate of micronucleated polychromatic erythrocytes induced by the administration of a mutagenic compound. For this, biological assumptions are made both on the erythropoietic system and on the mechanisms of actions of the compound. Its pharmacokinetic profile is also taken into account and it is linked to the induced toxicological effect. The model has been evaluated by analyzing the induction of micronuclei in mice bone marrow by a mutagenic compound, 6-mercaptopurine (6-mp). The analysis enabled to make interesting remarks about the induction of micronuclei by 6-mp and to put light on unsuspected wavy kinetics by optimizing the experimental design of the in vivo micronucleus assay.