**9. Conclusion**

Long-term toxicity resulting from off-target effects of TKIs can be assessed conveniently by administering TKIs via the drinking water to juvenile male Wistar rats over a prolonged period. During all developmental phases (prepubertal, puberty, postpubertal, and adult), drug blood levels are obtained corresponding to data in humans. The juvenile animal model disclosed reduced long bone length and diminished vertebral height combined with reduced bone mass density and reduced breaking strength dose-dependently after chronic exposure to imatinib. Thus, the juvenile animal model depicted here mimics perfectly clinical observations on osseous changes observed in pediatric patients with CML. Furthermore, intermittent exposure of the high TKI dose mitigated the skeletal side effect and therefore represented a possible treatment option for pediatric patients suffering from longitudinal growth retardation under imatinib therapy. The juvenile animal model might also be of value to predict sequelae of TKI treatment in other human organs following exposure over decades.
