BEHAVIORAL DISTURBANCES AND VESTIBULAR PATHOLOGY FOLLOWING CROTONITRILE EXPOSURE IN RATS

The dinitrile compound 3,3' -iminodipropionitrile causes a number of t oxic effects in sensory systems, including degeneration of the vestibu lar sensory hair cells, as well as a neurofilamentous pathology in mot or and sensory neurons. The chemical also causes permanent changes in behavior. These were initially attributed to the effect on neurofilame nts, but have been recently linked to the vestibular toxicity. The pre sent work studied the behavioral and pathological effects of the monon itrile compound crotonitrile. Adult male Long-Evans rats (n = 8/group) were exposed to crotonitrile (0, 100, 125, 150 mg/kg/day, for 3 days, ip, in 1 ml/kg corn oil) and assessed for changes in rearing activity , locomotor activity, and rating scores in tests of vestibular functio n. Surface preparations of the vestibular sensory epithelia were obser ved for hair cell loss by scanning electron microscopy (n = 3/ group). Control (n = 2) and 3 x 150 mg/kg crotonitrile (n = 3) rats were asse ssed for neurofilament accumulation in vestibular and dorsal root gang lion neurons by light microscopy observation of semithin sections from plastic-embedded ganglia. Crotonitrile dose-dependently increased loc omotor activity and rating scores for vestibular dysfunction. A dose-d ependent loss of vestibular hair cells was observed in the same animal s. In contrast, no obvious neurofilament accumulations were observed i n vestibular and dorsal root neurons. We conclude that vestibular toxi city is a property of the nitrile group, and that behavioral disturban ces ensue from this toxic action.