The focus of the proposed study is to examine the acute and chronic effects of ototoxic preparations on the electrophysiologic activity of the cochlea, VIII nerve, and brainstem through noninvasive electrocochleography (ECOG) and the auditory brainstem response (ABR). The primary purpose is to determine if changes in the ECOG or ABR can be used to predict impending hearing loss or provide early identification of a hearing loss before it is irreversible. If these measures do provide such an indicant, the efficacy of patient care may be enhanced. Experiments will begin with the development of noninvasive ECOG recording techniques from the tympanic membrane (TM) and ear canal of chinchillas needed for the subsequent chronic animal study of ototoxicity. Simultaneously recorded noninvasive and invasive measures of the summating potential (SP) amplitude, action potential (AP) amplitude, AP latency, and AP threshold will then be compared. Development of noninvasive ECOG recording techniques in these animals will eliminate the need for surgery, particularly repeated surgery , in may animal studies by ourselves and others. Consequently, the need for postoperative analgesics and antibiotics and sterile operating rooms could be markedly curtailed as well as possible animal suffering in chronic experiments. Then the noninvasive recording techniques developed in animals and previously developed noninvasive recording techniques from the TM in adult humans will be used to examine the chronic effects of ototoxic agents on SP amplitude, AP amplitude, the SP/AP amplitude ratio, AP latency-intensity functions, AP input-output functions, AP and ABR threshold and adaptation and the I-V interval of the auditory brainstem response. In the human adults, behavioral audiometric thresholds will also be monitored. In the animals, histology of the cochlea will be performed after sacrifice. In the third year, we plan to expand animal studies to include single unit studies of ototoxicity, and frequency selectivity either in single unit recordings, ECOG recordings, or both. In addition, we plan to expand the development of noninvasive electrocochleographic techniques to infants and neonates. Infants and neonates receiving ototoxic agents could then be included for study. Throughout the grant period the P.I. will take formal coursework in chemistry, pharmacology, and electron microscopy. Simultaneously, she will teach and supervise otolaryngology residents, medical students, and pharmacology doctoral students in the area of ECOG, ABR, and ototoxicity.