Experimental Studies

Many reports have identified ototoxic substances in animals, including dogs and cats. Some of the ingredients found in topical preparations that are safely used on the skin in the external ear canal can cause damage to the respiratory tissues that line the middle ear cavity and to the nervous structures in the inner ear.

Many experimental trials demonstrating ototoxic potential are done in normal laboratory animals. They involve placing medication or ear cleaners directly into one of the tympanic bullae for several days. Usually saline is infused into the opposite bulla as a negative control. But for a positive contol, gentamicin infusion into the tympanic cavity of laboratory animals may be substituted. In ototoxicity studies, brain- auditory-evoked-response (BAER) testing is done to determine hearing loss prior to euthanizing the experimental animals. Cochlear damage occurs initially in the cells detecting high-frequency sounds, so these animals first lose the ability to detect high- pitched sounds. Neurologic examinations are used to assess the function of the vestibular system. Screening for ototoxicy using the BAER test during safety tests of any otic drug or chemical should be done before its release for use in animals.

Histopathologic analyses of the tympanic bulla and the inner ear from these experimental animals are used to verify evidence of damage to the epithelium of the bulla or to the neurologic structures in the inner ear.

Care is prudent in interpreting the studies done in laboratory animals and extrap­olating the results to dogs and cats with diseased middle ears.

In another study that used juvenile guinea pigs to compare the ototoxicity of polymyxin and gentamicin directly instilled into the bullae, it was determined that the polymyxin group showed a 66% loss of cochlear hair cells compared with a 6.5% loss with gentamicin.⁵ In human medicine, most people with gentamicin ototoxicity have vestibulotoxicity rather than deafness. It has been estimated that up to 1% of the human population has a genetic predisposition to gentamicin ototoxicity.⁶

Ticarcillin (Ticar, SmithKline, Beecham) and ticarcillin with clavulanate potassium (Timentin, SmithKline, Beecham) have been successfully used topically and parenter­ally for the treatment of refractory Pseudomonas otitis externa and media.⁷ However, chinchilla studies using these compounds have demonstrated significant pathologic effects when they were injected as single applications into normal middle ears.⁸

Can a medication toxic to one species of animal also be ototoxic to another? Can a substance toxic to the cochlea in one species show toxicity to the vestibular appa­ratus in another species? It is possible that there are genetic differences among animals that confer susceptibility to certain drugs and chemicals, but most of these are undocumented.