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-This study was designed to evaluate changes in auditory brainstem response (ABR) in the course of auditory disturbance in rats induced by Kanamycin (KM). KM was administered subcutaneously to 12 CD (SD) male rats aged 6 weeks for 10 days at a dose of 800 mg/kg. Death was observed in one male on day 8 and 2 males on day 10. It was thought that kidney damage was the cause of death from histopathological findings. ABR was recorded before KM treatment and on days 4, 8, 10 and 11 after KM treatment. The ABR changes after KM treatment in rats were as follows. On day 4, 6 rats showed an increase in amplitude of waves I and/or II and on day 8, among those, 4 rats still showed a high amplitude of waves I and/or II. On day 8, 2 rats showed an elevation of ABR threshold (15-40 dB SPL) and a decrease in amplitude of wave I and increase in amplitude of wave II at the same time. On day 11, 7 rats showed a decrease in amplitude of wave I. In addition, ABR threshold shifts 10-70 dB SPL were observed in those rats. In ABR recording, KM-induced auditory disturbance model rats showed an increase in amplitude of waves I and/or II earlier than an ABR threshold shift. By analyzing temporal alteration of amplitude of the ABR components, we could detect precursory phenomenon of the auditory disturbance at an early phase of treatment. By following the pathway of click-ABR and tone pip-ABR examination, the auditory disturbance of low-frequency to high-frequency range could be analyzed at an early date in detail.

Scanning electron microscopic observation of the organ of Corti was conducted in kanamycin (KM)-treated beagle dogs, which were subjected to time lapse recording of auditory brainstem response (ABR). KM was administered subcutaneously 5 times per week to 4 beagle dogs at doses of 250 and 500mg/kg for 3-6weeks (a total dose of 4,750 to 7,000mg/kg). The animals were subjected to pathological examination when definite changes in ABR appeared.Severity of morphological changes were closely related with the degree of the ABR change and histopathological renal lesion.In the animals with slightly decreased amplitude of wave I of ABR also exhibited only a slight renal lesion. The organ of Corti, however, showed essentially a normal structure in these animals.In the animal manifesting moderate ABR change, renal lesion was moderate and the change of the hair cell in the organ of Corti was slight.The animal with such severe auditory disturbance as flattened ABR waveform showed a severe renal lesion and almost complete damages of the hair cells in the organ of Corti.In the present observation, the characteristics of KM-induced lesion in the organ of Corti in dogs are essentially the same with in other species. In addition, the examination of hearing ability could be done as an item during the course of routine long-term repeated dose study using dogs. (J Toxicol Pathol 7: 8186, 1994)

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