pralidoxime and acephate

Acephate (AP) is a widely available organophosphorus (OP) insecticide considered to have low mammalian toxicity. In plants and insects, AP is metabolized extensively to methamidophos (MP), a more potent OP insecticide. The limited mammalian metabolism of AP to MP has been studied in laboratory rat models and suggests that initial formation of MP from AP may inhibit further formation. No case reports of human ingestion with urine AP and MP levels have been previously published.. A 4-year-old male being evaluated for altered mental status and head trauma was noted to have muscarinic and nicotinic cholinergic signs. Further history suggested possible ingestion of a commercial AP product at an unknown time. Ingestion of AP was confirmed by the presence of urinary AP and MP and severely depressed red blood cell (RBC) cholinesterase and pseudocholinesterase activity levels. The patient initially received atropine in two 0.02 mg/kg IV boluses, then was started on 0.05 mg/kg IV per hour and titrated accordingly to clinical signs of cholinergic toxicity. Pralidoxime was also given at 20 mg/kg IV bolus, followed by an infusion of 10 mg/kg per hour. The patient required mechanical ventilation for 18 days and atropine infusion for 20 days. After a complicated intensive care unit course, he recovered and was discharged after a total of 32 days of hospitalization.. Four urine samples collected at different times were analyzed for AP and MP by using high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. Kinetic calculations were performed by using standard equations.. Suspected ingestion was confirmed by the presence of AP and MP in urine. The amount of MP found in urine suggests some limited human metabolism to this more toxic compound.. Urinary elimination kinetics of AP demonstrates low metabolic conversion of AP to MP in humans.

Topics: Antidotes; Atmospheric Pressure; Atropine; Butyrylcholinesterase; Child, Preschool; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Erythrocytes; Humans; Insecticides; Male; Muscarinic Antagonists; Organothiophosphorus Compounds; Phosphoramides; Poisoning; Pralidoxime Compounds; Respiration, Artificial; Tandem Mass Spectrometry; Treatment Outcome

Topics: Acetylcholinesterase; Adipose Tissue; Animals; Arkansas; Body Weight; Cholinesterase Inhibitors; Cholinesterase Reactivators; Cholinesterases; Crops, Agricultural; Environmental Monitoring; Gossypium; Insecticides; Malathion; Organophosphorus Compounds; Organothiophosphorus Compounds; Passeriformes; Phosphoramides; Pralidoxime Compounds

The toxicity of acephate to four species of aquatic insects, as well as the metabolism and cholinesterase-inhibiting properties of the chemical in the rat were studied. The results indicated that mayfly larvae were very sensitive to the toxic effects of acephate, whereas larvae of the stonefly, damselfly and mosquito were much less sensitive. In the rat, orally-administered acephate was rapidly absorbed from the intestines and severely inhibited the cholinesterases in the blood and brain. The enzymes began to recover after 24 hours, while the chemical was completely eliminated within three days. The amount of methamidophos observed in the liver was extremely low. The cholinesterase-inhibiting properties of acephate and methamidophos were compared in vitro to that of paraoxon, a known strong anticholinesterase. Enzymes from four vertebrates were used. In all cases, except one, acephate was found to be six orders of magnitude weaker than paraoxon, whereas methamidophos was three orders weaker. Trout brain cholinesterase was the exception; it was as sensitive to paraoxon as it was to methamidophos. Finally, four cholinesterases were inhibited with methamidophos, and their ability to reactivate spontaneously or to recover by induction with pyridine aldoxime methiodide (PAM) in vitro were determined. The results suggested that methamidophos-inhibited cholinesterases did not reactivate spontaneously; instead the enzymes remained inhibited either in a phosphorylated or an aged state. The significance of these results are discussed in relation to the use of acephate for forest insect pests.

Topics: Animals; Cholinesterase Inhibitors; Cholinesterase Reactivators; Erythrocytes; Insecta; Insecticides; Lethal Dose 50; Liver; Organothiophosphorus Compounds; Paraoxon; Phosphoramides; Pralidoxime Compounds; Rats; Rats, Inbred Strains; Trout