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DEVELOPMENTAL NEUROTOXICITY FOLLOWING NEONATAL EXPOSURE TO 3,3'-IMINODIPROPIONITRILE IN THE RAT
Citation:
Crofton, K., M. Stanton, AND D. Peele. DEVELOPMENTAL NEUROTOXICITY FOLLOWING NEONATAL EXPOSURE TO 3,3'-IMINODIPROPIONITRILE IN THE RAT. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-93/361 (NTIS PB93228872), 1993.
Description:
Adult exposure to the neurotoxicant 3,3'-iminodipropionitrile (IDPN) induces a hyperkinetic syndrome consisting of spontaneous head movements, abnormal circling, backwards locomotion, and sensory disruption. e report here the behavioral effects of developmental exposure to IDPN in the rat. nimals were exposed (ip) to either saline, 75, 150, or 300 mg/kg/day on postnatal days (PND) 5-7. nimals were tested for: figure-8 maze activity (PND 13-60); olfactory discrimination learning (PND18&24); T-maze al tern at i on and po si t i on discrimination learning (PND25&26); acoustic startle response (PND23,61&62); and passive avoidance (PND70). n an attempt to better define the dose response, a separate group of animals were exposed to either saline 225 mg/kg/day (PND5-7) and tested in the activity, T-maze, and startle paradigms. nimals exposed to 225 mg/kg/day and 300 mg/kg/day had depressed weight gain, and lethality was 25% in the group. Signs of the hyperkinetic syndrome, evident in the 225 and 300 mg/kg/day groups 150, 225 and 300 mg/kg/day groups, persisted throughout the course of the study. IDPN exposed animals (300 mg/kg/day) were hyperactive on PND17-60, failing to develop habituation in the figure-eight maze until PND60. The acoustic startle response was depressed for the 225 and 300 mg/kg/day groups on PND24 only. uditory thresholds were elevated for a high-frequency (40 kHz).