Electrophysiological deficiency in peripheral nerve induced by treatment for 12 weeks with 2-butenenitrile, 3-butenenitrile, cis-2-pentenenitrile and 3,3-iminodipropionitrile in rats.
Motor and sensory conduction velocities and amplitudes of the sensory and motor action potentials of the tail nerve were studied in male Sprague-Dawley rats during subchronic oral treatment with three unsaturated aliphatic nitriles. The rats were given, by gastric intubation, doses of 10, 20 and 40 mg x kg(-1) 3-butenenitrile (allyl cyanide) and 25, 50 and 100 mg x kg(-1) of either cis/trans-2-butenenitrile (crotononitrile) or cis-2-pentenenitrile once a day, 5 days per week for 12 weeks. Moreover, 3,3'-iminodipropionitrile was administered likewise at doses of 25, 50 and 100 mg x kg(-1) as reference neurotoxicant. Oral administration of the three unsaturated nitriles produced deafness and absence of reaction when the animals were subject to droptest. Moreover, rats exhibited both time- and concentration-dependent decreases in motor and sensory conduction velocities and amplitudes of the sensory action potentials. Nerve conduction velocities were partially reversible after 8 weeks of recovery. Rats receiving 3,3'-iminodipropionitrile developed deafness, head weaving and significant irreversive deficiencies in all the electrophysiological parameters studied. Further toxicological studies with related unsaturated nitriles should be carried out to determine the potential importance of the cis/trans isomerism in the observed neurotoxicity.
Gagnaire
F
F
Department of Industrial and Experimental Toxicology, National Institut for Research and Safety, Vandoeuvre, France.
Marignac
B
B
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D003638:Deafness / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013997:Time Factors
D009570:Nitriles