Is delayed neurotoxicity a property of all organophosphorus compounds? A study with a model compound: parathion.
A recently reported hypothesis of other investigators that the induction of delayed neurotoxicity is a property of all organophosphorus compounds including parathion was evaluated in light of the inability of parathion to induce in our laboratory any clinical, histological, or biochemical signs of delayed neurotoxicity in hens following a very intensive dosing regimen. Parathion was administered orally or applied dermally as 1 mg/kg/day for 1 week and then the dose was increased by 1 mg/kg/day at weekly intervals up to 6 mg/kg/day which was given thereafter until a total of 90 doses. Results indicate that parathion either orally or dermally did not produce delayed neurotoxicity in hens comparable to that induced by tri-orthocresyl phosphate (TOCP) in this experiment. This finding is supported by clinical, histological, and biochemical evidences. No clinical signs or histopathological changes in spinal cords and sciatic nerves of the type associated with delayed neurotoxicity were observed in any of the surviving parathion-treated hens. Moreover, this extensive treatment with parathion resulted in no significant in vivo effect on neurotoxic esterase, an esterase believed to be the initial target in the genesis of delayed neurotoxicity. These results agree with the general hypothesis that delayed neurotoxicity is a special toxic effect of some but not all of the organophosphorus esters.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002645:Chickens; D002800:Cholinesterase Inhibitors; D003408:Cresols / Q000633:toxicity*; D005260:Female; D009422:Nervous System Diseases / Q000139:chemically induced*; D009943:Organophosphorus Compounds / Q000633:toxicity; D010278:Parathion / Q000008:administration & dosage / Q000633:toxicity*; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014317:Tritolyl Phosphates / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D003408:Cresols; D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; D010278:Parathion; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase; C025541:tri-o-cresyl phosphate