Behavioral disturbances and vestibular pathology following crotonitrile exposure in rats

The dinitrile compound 3,3'-iminodipropionitrile causes a number of toxic effects in sensory systems, including degeneration of the vestibular sensory hair cells, as well as a neurofilamentous pathology in motor and sensory neurons. The chemical also causes permanent changes in behavior. These were initially attributed to the effect on neurofilaments, but have been recently linked to the vestibular toxicity. The present work studied the behavioral and pathological effects of the mononitrile compound crotonitrile. Adult male Long-Evans rats (n = 8/group) were exposed to crotonitrile (0, 100, 125, 150 mg/kg/day, for 3 days, i.p., in 1 ml/kg corn oil) and assessed for changes in rearing activity, locomotor activity, and rating scores in tests of vestibular function. Surface preparations of the vestibular sensory epithelia were observed 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 assessed for neurofilament accumulation in vestibular and dorsal root ganglion neurons by light microscopy observation of semi-thin sections from plastic-embedded ganglia. Crotonitrile dose-dependently increased locomotor activity and rating scores for vestibular dysfunction. A dose-dependent loss of vestibular hair cells was observed in the same animals. In contrast, no obvious neurofilament accumulations were observed in vestibular and dorsal root neurons. We conclude that vestibular toxicity is a property of the nitrile group, and that behavioral disturbances ensue from this toxic action.