Assessment of the acute acrylonitrile-induced neurotoxicity in rats.
Acrylonitrile (VCN) is an aliphatic nitrile which is used extensively in manufacturing of synthetic fibers, plastics, and rubber. Although the neurotoxicity of VCN is recognized, no thorough characterization of this effect has been reported. Current studies were designed to quantitatively characterize the acute phase of VCN-induced cholinomimetic neurotoxicity, and to determine the effects of dose, route of administration, and atropine on such toxicity. Administration of a single gavage or subcutaneous doses of 20, 40, or 80 mg VCN/kg to male Sprague-Dawley rats causes two distinctive phases of acute neurotoxic effects. Signs observed in the early phase had a rapid onset, and were cholinomimetic in nature. They included salivation, lacrimation, chromodacryorrhea, polyuria, miosis, vasodilatation in face, ears and extremities, increased gastric secretion, and diarrhea. A late phase developed hours after VCN dosing, and the toxic signs included depression, convulsions, and respiratory failure followed by death at high doses. These results revealed that the cholinomimetic toxicity induced by VCN was dose related regardless of the route of administration. In another study, rats were pretreated with atropine (1 mg/kg, IP) prior to VCN (40 mg/kg) in order to investigate the role of the cholinergic system. Atropine protected rats against VCN-induced cholinomimetic neurotoxicity, suggesting possible involvement of the cholinergic system. Finally, this work provides essential basic information for studying the biochemical, pharmacological, and neurological basis of VCN-induced neurotoxicity in the rat.
Ghanayem
B I
BI
Department of Pathology, Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Farooqui
M Y
MY
Elshabrawy
O
O
Mumtaz
M M
MM
Ahmed
A E
AE
D000181:Acrylonitrile / Q000008:administration & dosage / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001286:Atropine Derivatives / Q000494:pharmacology*; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D010277:Parasympathomimetics / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012463:Saliva / Q000187:drug effects / Q000378:metabolism*
D001286:Atropine Derivatives; D009498:Neurotoxins; D010277:Parasympathomimetics; D001285:Atropine; C006649:methylatropine; D000181:Acrylonitrile