Profound apprehension towards safety of irradiated food has remained a major cause behind tardy acceptance of this technology although it has immense socio-economic potential. Generation of in-depth scientific evidence will help to refute these apprehensions. With this prospective, the present study was undertaken where safety of various irradiated (D up to 25 kGy) foods was evaluated through long-term exposure studies in models including human lymphoblast TK6 cell line (100 generations) and Escherichia coli MG1655 cells (exclusive sub-culturing in irradiated food medium for 3000 generations). Additionally, the Ames test, micronucleus test, comet assay, DNA sequencing and restriction profiling of phagemid DNA from E. coli cells sub-cultured in irradiated food medium were also performed.