Auditory deficits and motor dysfunction following iminodipropionitrile administration in the rat.
The behavioral effects of 3,3'-iminodipropionitrile (IDPN) were studied using reflex modification of the acoustic startle response and figure-eight maze activity. A number of experiments were conducted with separate groups of adult male Long-Evans hooded rats exposed to saline or 50-500 mg/kg IDPN for 3 consecutive days. Auditory thresholds (reflex modification), motor activity, and grip strength were measured 1 day, and 1, 3, and 9 weeks postdosing. Reflex inhibition was monitored daily, prior to, during, and for 7 days following exposure. Auditory thresholds for 5- and 40-kHz tones were elevated approximately 25 dB and 50 dB, respectively. The onset of this auditory dysfunction in the 200-mg/kg/day group, as demonstrated by a loss of reflex inhibition, was 2 days for the 40-kHz tone and 4 days for the 5-kHz tone. Motor activity was increased up to 400% in the 200-mg/kg group, whereas there was no alteration in hindlimb grip strength. These data demonstrate dosage- and time-dependent alterations in auditory and motor function following IDPN exposure.
Crofton
K M
KM
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Knight
T
T
D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006311:Hearing Disorders / Q000139:chemically induced / Q000503:physiopathology; D007858:Learning; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D012016:Reference Values; D012022:Reflex, Acoustic / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D013997:Time Factors
D009570:Nitriles; C008110:3,3'-iminodipropionitrile