© 1985 Oxford University Press
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Toxic Effects on the Visual System of Diaminodiphenoxybutane, Quinine, and Ethambutol in Conscious Dogs
Central Research Division, Takeda Chemical Industries, Ltd. 6-10-1 Himuro-cho, Takatsuki, Osaka 569, Japan
Toxic Effects on the Visual System of Diaminodiphenoxybutane, Quinine, and Ethambutol in Conscious DOGS. SATO, S. (1985). Fundam Appl. Toxicol. 5, 777–784. The effects of diaminodiphenoxybutane (DAPB), quinine, and ethambutol (EB) on the electroretinogram (ERG) and the visual evoked potential (VEP) were examined in conscious dogs. In dogs receiving repeated oral doses of 100 mg/kg/day for 4 days or a single iv dose of 30 mg/kg of DAPB, the amplitudes of the ERG a- and b-waves were markedly depressed and the peak latency of the VEP first wave was prolonged. Thereafter, ophthalmoscopic changes consisted of mottled discoloration of the fundus, loss of visual placing reaction, and dilatation of the pupils with reduction of the pupillary light reflex were observed. These abnormal signs disappeared even though the marked depression in amplitudes of the ERG a- and b-waves and the prolongation in latency of the VEP first wave continued. A single iv dose of quinine at 50 mg/kg caused a slight depression of the amplitude of the ERG, whereas the VEP remained relatively unaffected. In a dog receiving a single iv dose of quinine at 100 mg/kg, both the ERG and VEP were depressed, and a slight dilatation of the pupils with reduction of the pupillary light reflex and an impairment of visual placing reaction were observed transiently. There was no abnormality in the ocular fundus in either animal receiving quinine. The dogs receiving repeated sc doses of EB at 100, 200, and 400 mg/kg/day for 4 weeks each, for a total of 12 weeks, showed extensive decoloration of the tapetal fundus. However, neither the ERG nor VEP showed any significant abnormalities, and no behavioral signs of visual disturbance were observed. These results indicate that DAPB and quinine directly damage retinal function and the decoloration of the tapetal fundus caused by EB is not directly related to retinal function. In addition, the procedure used in this study to record the ERG and VEP was found to be reliable for assessing the visual toxicity of drugs in conscious dogs.