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EFFECT OF 3,3'-IMINODIPROPIONITRILE ON THE PERIPHERAL STRUCTURES OF THE RATVISUAL SYSTEM
Citation:
Barone, Jr., S., D. Herr, AND K. Crofton. EFFECT OF 3,3'-IMINODIPROPIONITRILE ON THE PERIPHERAL STRUCTURES OF THE RATVISUAL SYSTEM. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/551.
Description:
Short-term repeated administration of 3,3'-iminodiproprionitrile (IDPN) results in a complex neurobehavioral syndrome that has been previously described (Thuiller and Burger, 1954). dult male Long-Evans rats received IDPN (400 mg/kg i.p.) and were killed, 1 day after one dose, or 1,3,7,35 or 70 day(s) following 3 consecutive daily doses for histological analysis of the eye. econd dose-response study (0,100,200, 400 mg/kg x 3 days), quantifying flash evoked potentials (FEPS) and retinal histology, was performed 2 wks after the 3rd IDPN dose. DPN exposure resulted in opacification of the cornea, and vascular hemorrhaging (3 days) followed by complete detachment of the retina (I week). he corneal opacification was transient and appeared to be resolved by 14 days post-treatment. arly necrosis in the inner nuclear (IN) layer was seen before retinal detachment (3 days after dosing) followed by progressive retinal degeneration (35 and 70 days). etinal detachment was less severe at 70 days. n the dose-response study, retina detachment and degeneration in the IN layer was apparent in the 40 mg/kg dose group (12 days after dosing). owever, increased GFAP immunoreactivity in the retina was observed in the 200 mg/kg dose group without overt retinal pathology. n the time-cause study, FEPs were recorded 1,3,7,14, and 35 days after the last dose of 400 mg/kg IDPN. ncrease latencies for peaks P21, N30, N56, P63, and N70 were observed throughout the study. he latency of pean P46 was increased except on day 35, while the latencies of later parts of FEPs peaks P90 and N160) were increased only on day 7. The amplitude of FEP peaks N56 and N70 were decreased, with recovery by the end of the experiment. n contrast, the amplitude of peak N160 was decreased at later times of the study. he amplitudes of peaks p63 and P90 were increased on day 3. In the dose-response study, decreased FEP peak N30 and N56 amplitudes, and increased latencies of peaks p21 and P46, were observed in a dose-related manner with significant decrements at the highest dose. esults indicate that the corneal opacification, vascular lesions, and detached retinas recovered in a time-dependant manner, while neurodegenera-tion of the visual retina was progressive, even after the retina as reattached. ose-related electrophysiological changes were observed, with statistical significance obtained at a ose level (400 mg/kg) which produced pathological alterations. The present study provides electrophysiological evidence that this neurotoxicant may have direct effects on CNS structures above the level of the brainstem.