Comparison of behavioral, vestibular, and axonal effects of subchronic IDPN in the rat

The effects of subchronic 3,3'-iminodipropionitrile (IDPN) were characterized in the adult Long-Evans male rat. In a preparatory experiment, acute IDPN (890 mg/kg, IP) and intratympanic arsanilic acid caused similar alterations in locomotor activity, rearings, and scores for vestibular impairment. In a second preparatory experiment, IDPN in the drinking water (0%, 0.025%, 0.05%, 0.1%, 0.2%, or 0.4%) caused a concentration-dependent decrease in water intake, but a effective increase in IDPN intake. In the subchronic experiment, rats were exposed to the above concentrations of IDPN for 15 weeks, except the 0.4% group, exposed for only 7 weeks. Effects on body weight, motor activity, vestibular scores, vestibular morphology, and axonal diameter were observed after 0.2% and 0.4% IDPN. Proximal axonopathies but little or no clinical signs or vestibular toxicity followed 0.05% and 0.1% IDPN. We concluded that vestibular hair cell loss can be induced by subchronic IDPN at doses larger than the axonopathic doses, and that the vestibular toxicity, not the axonopathy, is responsible for the gross changes in behavior characterizing IDPN exposure.