Prolonged Neurobehavioral and Visual Effects of Short-Term Exposure to 3,3'-Iminodipropionitrile (IDPN) in Rats

摘要

Strategies for neurotoxicity testing often include initial screening tests, suchas a functional observational battery (FOB) and motor activity assessment, followed by detailed characterization studies. In this study, a neurobehavioral screening battery (FOB and motor activity) was used to evaluate the effects of 3-day repeated exposure to 0, 100, 200, or 400 mg/kg/day 3,3'-iminodipropionitrile (IDPN). Adult Long-Evans rats (males and females) were tested before dosing and 1, 14, 28, 56, and 91 days after the third dose. IDPN initially produced generalized CNS depression, weakness, and hypothermia. Thereafter, marked hyperactivity, increased excitability, decreased reactivity to visual and auditory stimuli, neuromuscular weakness, equilibrium changes, and a 'waltzing syndrome' (vertical and lateral head movements, circling, and retropulsion) emerged and persisted for 3 months. Males were more severely affected than females. Following neurobehavioral testing, the rats were examined for visual function using flash (three intensities) and pattern (three pattern sizes by three contrast levels)-elicited visual evoked potentials (VEPs). IDPN produced