Nitriles are widely used in the manufacture of plastics, solvents and synthetic intermediates. Among the nitriles, allylnitrile and crotononitrile are known to induce behavioral abnormalities in rodents similar to the ECC syndrome (excitement, choreoathetosis and circling). Although the full mechanism underlying these abnormalities is not known, recent studies on these nitriles have revealed their toxicity to the central and peripheral nervous systems. Allylnitrile produces apoptotic changes in neurons in the habenular and raphe nuclei, and allylnitrile-induced apoptotic lesions in the median raphe nucleus may further stimulate the locomotor activity that is first stimulated by apoptotic lesions in the medial habenula. Moreover, the stability of allylnitrile-induced behavioral abnormalities may be dependent on apoptotic changes in the medial habenula and median raphe nucleus. Pathological changes in the cerebral cortex, hypothalamus, hippocampus and dentate gyrus seem to have no relevance to behavioral abnormalities. The GABAergic systems through the medial habenular nucleus-interpeduncular nucleus-ascending raphe nuclei relay and the substantia nigra may be involved in the mechanism underlying allylnitrile-induced behavioral abnormalities. In rats, both allylnitrile and crotononitrile cause loss of hair bundles in the crista, utricle and saccule, and the degree of loss is dose-dependent. The vestibular sensory epithelia are a target for both nitriles, and their degeneration may be responsible for some of the nitrile-induced behavioral syndrome. In rats, both nitriles cause auditory sensor epithelia degeneration, corneal opacity and gliosis in the retina and olfactory bulbs, however, these changes may have no relevance to the behavioral syndrome.
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