Urinary elimination kinetics of acephate and its metabolite, methamidophos, in urine after acute ingestion

Abstract

INTRODUCTIONAcephate (AP) is one of the few commercially available, over-thecounter organophosphorus (OP) insecticides in the US. It is considered one of the safest OP insecticides because of its low mammalian toxicity, with a lethal dose (LD50) of 360 mg/kg in mice and 900 mg/kg in rats [1]. The selective toxicity of AP is due reportedly to differential bioactivation and metabolism in insects compared to mammals; however, the exact mechanism is still unknown. In insects, AP is rapidly and extensively metabolized to a more potent OP insecticide-methamidophos (MP)-which has a lower LD50 of 14-30 mg/kg in mice and rats, thus Keywords: Acephate, methamidaphos, toxicokinetics, urine, poisoning Notes: This work was funded, in whole, by internal operating funds of the Centers for Disease Control and Prevention. There was no outside funding of any kind used for this study. ABSTRACTIntroduction: 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.Case Report: 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.Methods: 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.Results: 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.Conclusions: Urinary elimination kinetics of AP demonstrates low metabolic conversion of AP to MP in humans.

Detection of Pesticides and Metabolites Using Surface-Enhanced Raman Spectroscopy (SERS): Acephate

“…One concern with silver usage is that the ketone moiety uniquely differentiates acephate from its degradation product–metabolite methamidophos. 52 The SERS spectrum of methamidophos is presented in Fig. 4.…”

Developmental Neurotoxicity of Methamidophos in the Embryo-Larval Stages of Zebrafish

“…One of the concentrations of methamidophos exposure (25 μg/L) is close to environmentally relevant concentrations of methamidophos in the water environment of some regions, such as Philippines, India and other countries [ 28 ]. Besides, another concentration (500 μg/L) is near to the level of methamidophos in part of the human samples [ 29 , 51 , 52 ], which indicates that people in some countries are exposed to methamidophos in dangerous levels. Besides, many studies have reported that methamidophos concentration in fresh fruits and vegetables were higher than the FAO/WHO permissible limits residual levels [ 7 , 53 ].…”

“…This study was therefore designed to study methamidophos neurotoxicity and related mechanism in the early stages of zebrafish. Two environmentally relevant concentrations of methamidophos (25 and 500 μg/L) were selected, which were according to the concentration in water environment and the level in part of the human samples, respectively [ 28 , 29 ]. The analysis of locomotor behavior and apoptosis was used to assess the impairment of nervous system.…”

Organophosphorus Pesticides

“…A 4 year old child who had ingested acephate was brought to an emergency room exhibiting profound generalized weakness and depressed gag reflex (155). The child was placed on mechanical ventilation, given intravenous fluids, and vasopressors, and atropine and pralidoxime, monitored for 32 days and released.…”