Relative neurotoxicological properties of five unsaturated aliphatic nitriles in rats.
Motor and sensory conduction velocities (MCV and SCV) and amplitudes of the sensory and motor action potentials (ASAP and AMAP) of the tail nerve were studied in male Sprague-Dawley rats during chronic oral treatment with five unsaturated aliphatic nitriles. Rats were given doses of 12.5, 25 and 50 mg kg(-1) of acrylonitrile, 50, 70 and 90 mg kg(-1) of methacrylonitrile, 25, 50 and 100 mg kg(-1) of trans-3-pentenenitrile and 50, 100 and 200 mg kg(-1) of either 3-methyl-2-butenenitrile or 4-pentenenitrile once a day, 5 days per week for 12 weeks. Moreover, due the the early results obtained after oral treatment, neurophysiological examinations were also carried out in rats exposed by inhalation to 25, 50 and 100 ppm of acrylonitrile for 6 h a day, 5 days per week for 24 weeks. Rats given acrylonitrile orally developed behavioural sensitization characterized by salivation, locomotor hyperactivity and moderately intense stereotypies. Moreover, rats in the high dose group developed weakness in hindlimbs associated with decreases in SCV and ASAP. Rats exposed to acrylonitrile vapours exhibited time- and concentration-dependent decreases in MCV, SCV and ASAP, which were partially reversible after 8 weeks of recovery. None of the other four nitriles caused any abnormal behaviour or any changes in the electrophysiological parameters in spite of an obvious general toxicity. Based upon these results, it can be concluded that the nervous system of the rat appears to be a target following either oral or inhalation exposures of acrylonitrile.
Gagnaire
F
F
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Marignac
B
B
Bonnet
P
P
D000181:Acrylonitrile / Q000008:administration & dosage / Q000633:toxicity; D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006614:Hindlimb / Q000187:drug effects / Q000294:innervation; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D009570:Nitriles / Q000008:administration & dosage / Q000633:toxicity*; D010525:Peripheral Nerves / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship; D013623:Tail / Q000187:drug effects / Q000294:innervation; D013997:Time Factors
C111869:4-pentenenitrile; D008689:Methacrylates; D009570:Nitriles; C008385:methacrylonitrile; C111867:3-methyl-2-butenenitrile; D000181:Acrylonitrile