Stochastic modeling in toxicokinetics. Application to the in vivo micronucleus assay

A stochastic model for the in vivo micronucleus assay is presented. This mo del describes the kinetic of the rate of micronucleated polychromatic eryth rocytes induced by the administration of a mutagenic compound, For this, bi ological assumptions are made both on the erythropoietic system and on the mechanisms of action of the compound. Its pharmacokinetic profile is also t aken into account and it is linked to the induced toxicological effect. Thi s model has been evaluated by analyzing the induction of micronuclei is mic e bone marrow by a mutagenic compound, 6-mercaptopurine (6-mp), This analys is enabled to make interesting remarks about the induction of micronuclei b y 6-mp and to put to light an unsuspected wavy kinetic by optimizing the ex perimental design of the in vivo micronucleus assay, (C) 2001 Elsevier Scie nce Inc. All rights reserved.