THE TOXICITY OF IDPN ON THE VESTIBULAR SYSTEM OF THE RAT - NEW INSIGHTS ON ITS EFFECTS ON BEHAVIOR AND NEUROFILAMENT TRANSPORT

3,3 '-iminodipropionitrile (IDPN) causes a permanent syndrome of abnor malities in spontaneous behavior and a deficit in the axonal transport of neurofilaments (NF). Male Long-Evans rats were given IDPN (0, 200, 400, 600, or 1000 mg/kg, ip, in saline) and assessed for behaviors in dicative of vestibular function at 1 weekpost-dosing. The morphology o f the peripheral vestibular system in animals dosed with 0, 200, 400, 600, 800, or 1000 mg/ kg of IDPN was assessed at 4 days post-dosing by light microscopy on semithin sections. Animals receiving 1000, 1500, or 2000 mg/kg of IDPN were assessed for morphological alterations in t he vestibular ganglion at 8 days post-dosing. Behavioral data indicate d a dose-dependent loss of vestibular function after IDPN, the vestibu lar deficits first appearing at the 400 mg/kg dose level. IDPN exposur e was also observed to result in degeneration of the vestibular sensor y hair cells. Degenerative changes were already found at the 400 mg/kg dose level, and were extensive after 1000 mg/kg. In the ganglion neur ons, no effects were observed after 1000 mg/kg of IDPN, but perikaryal accumulations of NF were found after 1500 or 2000 mg/kg. In conclusio n, the data showed that low doses of IDPN are toxic to the vestibular hair cells, and suggest a link between this action and the effects of the chemical on spontaneous behavior. In addition, doses of IDPN large r than those required for toxicity to the vestibular sensory cells, in duced accumulations of NF in the myelinated cell bodies of the vestibu lar ganglion neurons. This action differs from the classically describ ed IDPN-induced accumulation of NF in the first proximal internodes of the large myelinated axons, and suggests that IDPN may interfere with the control of NF metabolism by the myelinating Schwann cells. (C) 19 94 Intox Press, Inc.