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The GEANT4 Monte Carlo radiation transport toolkit, developed by the RD44 and GEANT4 Collaborations, aims to become a tool of generalized application in high energy physics, nuclear physics, astrophysics, and medical physics research. Due to its object-oriented design, GEANT4 is a distinct new approach for the development of flexible simulation applications. A wide energy range coverage for both electromagnetic and hadronic physics processes is offered. GEANT4 provides also an optical physics process category, allowing the production and propagation of scintillation and Cherenkov emitted light to be described. Such capabilities are well tailored for the requirements of the new generation of astrophysics experiments to be installed on the International Space Station, like EUSO and AMS. In this paper, the system architecture of a GEANT4 based simulation framework and its application to EUSO/ULTRA and AMS/RICH performance studies are presented.