The Significance of Inhibition of Nonspecific Esterases in the Development of Organophosphorus-Induced Delayed Neurotoxicity.
Abou-Donia-MB; Lapadula-DM; Carrington-CD; Nomeir-AA
Cholinesterases: Fundamental and Applied Aspects 1984:447-461
The effects of oral and dermal administration of S,S,S-tri-n-butyl- phosphorotrithioate (78488) (DEF) were investigated on specific enzymes in the nervous system. Laying leghorn-hens were treated with DEF, tri-o-cresyl-phosphate (78308), or parathion (56382). DEF was able to produce three toxic effects: acute cholinergic effect occurring shortly after exposure as the result of acetylcholinesterase (AChE) inhibition; late acute effect occurring 2 to 4 days after oral administration of large DEF doses which resulted from n-butyl-mercaptan toxicity and caused hematotoxicity, loss of appetite and weight, weakness, emaciation, paralysis, and death and was neither related to AChE inhibition or associated with histopathological changes in nerve tissues; and delayed neurotoxicity occurring 6 to 14 days after dermal application, causing axonal and myelin degeneration along with ataxia, paralysis, and death. While dermal dosing with DEF significantly inhibited brain neurotoxic esterase (NTE), oral administration did not inhibit NTE, and also failed to produce organophosphorus compound induced delayed neurotoxicity.
NIOSH-Grant; Neurotoxic-effects; Organo-phosphorus-compounds; Organo-phosphorus-pesticides; Central-nervous-system; Agricultural-chemicals; Herbicides; Brain-damage; Defoliants; Plasticizers;
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
78-48-8; 78-30-8; 56-38-2;
Brzin-M; Barnard-EA; Sket-D;
Neurotoxic Disorders; Neurotoxic-effects;
Cholinesterases: Fundamental and Applied Aspects
Duke University, Durham, North Carolina