Behavioral disturbances and hair cell loss in the inner ear following nitrile exposure in mice, guinea pigs, and frogs.

Several nitriles have been demonstrated to cause hair cell loss in the inner ear of the rat, but the susceptibility of other species to this toxic effect has not been investigated. Adult male Swiss mice were administered (po) control vehicle, cis-crotononitrile (2.75 mmol/kg), or 3,3'-iminodipropionitrile (IDPN, at 8, 16, and 24 mmol/kg), and the changes in vestibular function were assessed by behavioral endpoints. In addition, surface preparations of the vestibular sensory epithelia were examined for hair cell loss using scanning electron microscopy (SEM). IDPN, in a dose-dependent manner, and cis-crotononitrile induced both vestibular dysfunction and loss of hair bundles. Male Dunkin Hartley guinea pigs were administered IDPN (0, 1.6, 2.4, or 3.2 mmol/kg, ip), and their vestibular and auditory sensory epithelia were examined by SEM. The guinea pigs developed behavioral abnormalities indicative of vestibular dysfunction, with more overt effects observed in the animals treated with larger doses, and displayed a dose-dependent loss of hair bundles in both the vestibular and the auditory epithelia. Frogs (Rana perezi) were administered IDPN (0, 16, 24, or 32 mmol/kg, ip), and their sensory epithelia in the inner ear were examined by SEM. IDPN caused behavioral abnormalities indicative of vestibular dysfunction and loss of hair bundles. We conclude that some nitriles are thorough ototoxic compounds affecting hair cells in a wide range of species. This conclusion highlights the potential interest of this toxic effect and offers new animal models in which to decipher its basis.