Behavioural disturbances and sensory pathology following allylnitrile exposure in rats

Animals exposed to allylnitrile develop permanent abnormalities in motor behaviour, similar to those caused by 3,3'-iminodipropionitrile (IDPN) and crotononitrile. IDPN and crotononitrile effects have been attributed to vestibular hair cell degeneration, but allylnitrile has been suggested to modify behaviour through neuronal degeneration in the CNS. Adult male Long-Evans rats were exposed to allylnitrile (0, 20, 40, 60 mg/kg per day, for 3 days) and the changes in rearing activity and rating scores in tests of vestibular function were assessed. Surface preparations of the vestibular sensory epithelia and the organ of Corti were observed for hair cell loss by scanning electron microscopy. Corneal transparency and concentrations in retina and olfactory bulbs of glial fibrillary acidic protein (GFAP), a marker for reactive gliosis, were also determined, as they are known targets of IDPN toxicity. In a dose-dependent manner, allylnitrile caused corneal opacity and gliosis in the retina and olfactory bulbs, decreased rearing activity and increased the rating scores in tests of vestibular dysfunction, and induced hair cell loss in both the vestibular sensory epithelia and the organ of Corti. The behavioural deficits correlated well with the loss of vestibular hair cells. We conclude that allylnitrile causes permanent modifications in behaviour by loss of vestibular function as IDPN and crotononitrile do and that all these chemicals share other toxic targets, such as the cornea, the retina, and the olfactory system. Data reported here and elsewhere indicate that a number of nitriles show similar neurotoxic properties.