Ototoxicity: An argument for evaluation of the cochlea in safety testing in animals

The cochlea is one of the more common targets for toxic effects, yet curren t toxicologic screening in animals does nor routinely evaluate the cochlea as a potential target organ. Although histopathologic sections are routinel y taken from the rye and the optic nerve and tract and most studies include at least 1 section through the nasal cavity and olfactory mucosa, the coch lea is not histopathologically examined in routine toxicity studies. Unfort unately, routine clinical examinations frequently miss ototoxicity because rodents and other species can lose most of their high-frequency hearing and still respond to most ambient noises. Ototoxicity as a deficiency in toxic ologic screening can be remedied by using well-established histopathologic and behavior al methods or electrophysiologic methods, such as brain stem a uditory evoked responses (BAERs). Once the equipment is in place, BAERs can be obtained quickly and easily for ototoxicity screening (approximately 15 minutes for paired testing of 2 rats and 30 minutes each for dogs). BAERs also can be used in virtually all mammalian species. Three or 4 probe frequ encies (eg, 4, 8, 16, and 32 kHz), representing different areas of the coch lea, can be tested in a few minutes with subcutaneous electrodes under shor t-acting chemorestraint. Given the availability of several approaches to sc reening for ototoxicity and the importance of the auditory function in huma n health, safety tests of chemicals and drugs should include an effective s creening test for ototoxicity.