OTOTOXICITY IN DEVELOPING MAMMALS

Developing mammals are more sensitive to noise, chemical and drug-induced ototoxicity than adults, with maximum sensitivity occurring during periods of anatomical and functional maturation of the cochlea. Normal physiological development of resting potentials (the endocochlear potential) and sound-evoked potentials including cochlear microphonics, summating potentials, compound action potentials, auditory brainstem responses and more recently distortion-product otoacoustic emissions have been characterized in several species including rats, mice, kittens, gerbils and guinea pigs. All of these responses are significantly impaired following acoustic trauma and/or exposure to a variety of ototoxic agents including aminoglycoside antibiotics, loop diuretics, antithyroid and antitumor drugs (alpha-difluoromethylornithine) and excitatory amino acids. Coupled with physiological and anatomical development is the maturation of specific biochemical pathways, which may be vulnerable targets of environmental noise and chemicals, excitatory amino acids and therapeutic drugs with ototoxic potentials.