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Ototoxicity is a leading cause of acquired hearing loss and intake of ototoxic medicines can result in inner ear damage and hearing loss. While ototoxicity assessment is well defined for drugs administered via the otic route or those expected to reach the inner ear during clinical use, it is not required for other therapeutic areas. Hence, more than 200 marketed medications have been reported to be ototoxic postmarketing. Ototoxicity testing programs should be adapted to the type of therapy, its indication (targeting the ear or potentially ototoxic), and the number of assets to test. For multiple molecules and/or multiple concentrations, screening options are available: in vitro (otic cell assays), ex vivo (cochlear explant), and in vivo (in zebrafish). Besides assessing the ototoxicity of a drug, it may also be useful to compare its ototoxicity to that of a well-known drug of a similar class. Screening assays provide a streamlined and rapid method to know whether a drug is safe for inner ear structures. The purpose of this study was to establish robust in vitro, and ex vivo models to rapidly evaluate ototoxicity of drugs and chemical compounds. 1 – In vitro HEI-OC1 otic cells were exposed to cisplatin at 5 different concentrations. Cell metabolism (MTT assay) and cell numbers (CCK8 assay) were evaluated. Different concentrations of cisplatin were used and demonstrated a clear dose effect on the survival of the HEI-OC1 cells as well as on the cell's metabolic activity. A concentration of 100–200 µM induced adequate cytotoxicity. A positive control, the antioxidant N-Acetylcysteine (NAC) was able to demonstrate a dose-dependent rescue against cisplatin toxicity. Two other toxic stimuli, high glucose and gentamicin, were also tested. When exposed, cells produced more ROS and entered apoptosis quicker. Those tests show that our model can be applied to evaluate the ototoxicity of different molecules other than cisplatin. 2 – Ex vivo Rodent cochlear explants were incubated and treated with various concentrations of cisplatin and for different exposure durations. Labeling of the tissues with phalloidin and Myosin 7a showed a significant decrease of hair cells in the cisplatin group compared to the sham group. The extent of the damage inflicted on the Organ of Corti was represented by a disorganization score. Cisplatin exposed tissues were graded with the maximum score whereas the untreated tissues were unscathed. This scale helps us in the assessment of histological damage on cochlear explants when exposed to harmful molecules. These results allowed us to establish robust cisplatinbased models for in vitro, and ex vivo ototoxicity screening, allowing the assessment of potential ototoxicity properties earlier in the drug development process, thus reducing cost, and potential clinical risks.