crotononitrile and Body-Weight

Animals exposed to 3,3'-iminodipropionitrile (IDPN) or to several similar nitriles develop a permanent syndrome of behavioral abnormalities. The present work addressed the hypothesis that this syndrome is caused by a toxic effect of these nitriles on the peripheral vestibular system. Male Long-Evans rats were given acute doses of IDPN (0, 200, 400, 600, or 1000 mg/kg, ip) and assessed for a number of behaviors indicative of vestibular function at postdosing times ranging from 1 day to 9 weeks. The pathological effects of IDPN on the morphology of the vestibular sensory epithelia were studied by scanning electron microscopy at 1,2,4, and 21 days after exposure. The behavioral study revealed dose-dependent deficits in vestibular function after IDPN. Alterations in vestibular morphology occurred at the same doses of IDPN that induced behavioral changes (400-1000 mg/kg). The pathological alterations after IDPN consisted of degeneration of the vestibular sensory hair cells, and no hair cells remained in the vestibular receptors 3 weeks after the 1000 mg/kg dose. A good correlation was also found for the time-course characteristics of the behavioral and the morphopathological effects of IDPN. The vestibular sensory epithelia displayed a regional pattern of differential sensitivity to the toxic effect of IDPN. Both intraepithelial and interepithelial differences in sensitivity were found. Crotonitrile (250 mg/kg, ip), which induces the same behavioral syndrome, was found to induce also degeneration of the vestibular hair cells. We conclude that IDPN and the similar nitriles that cause the same behavioral abnormalities are toxic to the peripheral vestibular system.

Topics: Animals; Behavior, Animal; Body Weight; Dose-Response Relationship, Drug; Hair Cells, Vestibular; Male; Neurotoxins; Nitriles; Rats

The developmental toxicities of eight aliphatic mononitriles were studied in Sprague-Dawley rats after inhalation exposure for 6 hr/day, during Days 6 to 20 of gestation. The range of exposure concentrations for acetonitrile was 900 to 1800 ppm; for propionitrile and n-butyronitrile, 50 to 200 ppm; for isobutyronitrile, 50 to 300 ppm; for acrylonitrile and methacrylonitrile, 12 to 100 ppm; for allylnitrile 12 to 50 ppm; and for 2-chloroacrylonitrile, 1 to 12 ppm. Embryolethality was observed after exposure to 1800 ppm acetonitrile, 200 ppm propionitrile, 300 ppm isobutyronitrile; fetotoxicity was observed after exposure to 200 ppm propionitrile, n-butyronitrile, or isobutyronitrile, or to 25 ppm acrylonitrile in the presence of overt signs of maternal toxicity. In the absence of significant maternal toxicity, allylnitrile caused embryolethality, fetotoxicity, and clear teratogenicity at 50 ppm, and n-butyronitrile and methacrylonitrile caused fetotoxicity at 200 ppm and 100 ppm, respectively. While maternal toxicity was observed for 2-chloroacrylonitrile, it did not cause significant embryonal or fetal toxicity up to 12 ppm.

Topics: Acetonitriles; Administration, Inhalation; Animals; Body Weight; Embryo, Mammalian; Female; Fetus; Male; Nitriles; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction; Teratogens