Ototoxicity

Abstract

Ototoxicity is the process by which chemicals cause damage to the end organs of hearing (the cochlea) or balance (the vestibular system). Hearing loss is the common effect of ototoxins, although many also affect the vestibular system. Some cause temporary hearing loss (e.g. the ‘loop’ diuretics or salicylates). However, the most significant group of ototoxic agents cause death of the sensory hair cells (HCs) and permanent hearing loss, for example aminoglycoside antibiotics, cis ‐platinum and organic solvents. In mammalian species the HC losses caused by these agents are permanent because, unlike the sensory epithelia in the inner ear in birds and other nonmammalian vertebrates, there is no capacity for HC regeneration. The effects generally develop only after repeated administration, but in some cases a single administration is sufficient (e.g. trimethyltin). Drug interactions can result in much greater damage than would be expected from the single agents. Excess noise can also cause HC death and can act synergistically with ototoxic chemicals. The most characteristic pattern of damage is predominantly death of outer HCs initially at the base of the cochlea (affecting high frequency hearing). Among humans, some individuals may be genetically predisposed to ototoxic damage.