[Allylnitrile-induced behavioral abnormalities and findings relating to the mechanism underlying behavioral...

Nitriles are widely used in industry as plastics, solvents, and synthetic intermediates. It has been shown that the thermal degradation of acrylonitrile-based plastics leads to the emission of a great variety of nitriles. Exposure of humans and experimental animals to some nitriles has been shown to lead to disorders of the central nervous, hepatic, cardiovascular, renal, and gastrointestinal systems. Iminodipropionitrile has long been known to induce in experimental animals behavioral syndromes that other nitriles have not been reported to induce. Recently, we have found that a single administration of allylnitrile, an analog of acrylonitrile, induces in rodents behavioral abnormalities including head twitching, head weaving, random circling, increased locomotor activity, backward pedaling, pivoting, and somersaulting. The induced abnormalities were persistent. Crotononitrile and 2-pentenenitrile also are able to produce behavioral abnormalities. Thus, the nitriles appear as a new class of neurotoxic compounds with potential relevance to the human health. The mechanism by which allylnitrile induces and maintains the behavioral abnormalities is summarised below. 1. Allylnitrile activates the serotonin (5-HT) system in the central nervous system, and as a consequence activation of 5-HT-2 receptors due to increased 5-HT may lead to induction of head twitching. 2. Although the data available indicate that the dopamine (DA) system may be involved in allylnitrile-induced behavioral abnormalities, it remains unknown how the DA system relates to the abnormalities. 3. Allylnitrile decreases the noradrenaline level in the central nervous system, which is thought to be secondary to the 5-HT system activation mentioned above. The allylnitrile-induced head twitching, however, may occur in consequence to both enhanced beta-adrenoceptor stimulation and to the removal of tonic inhibitory control by alpha-2-adrenoceptors. 4. The neuropathological data indicate an important role of the medial habenular and raphe nuclei in allylnitrile-induced behavioral abnormalities. Onset of the behavioral abnormalities appears to be associated with the impairment in the medial habenulo-raphe relay owing to activation of apoptotic cascade in neurons. 5. On the basis of the findings with iminodipropionitrile and crotononitrile, allylnitrile might produce pathological changes in the vestibular sensory hair cells. Further studies are needed to explore the mechanism underlying the allylnitrile-induced syndromes.