Distribution and excretion of [14CH3S]methamidophos after intravenous administration of a toxic dose and the relationship with anticholinesterase activity |
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| Authors: | AJ Gray CM Thompson TR Fukuto |
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| Institution: | 1. Division of Toxicology and Physiology, Department of Entomology, University of California, Riverside, California 92521 USA;2. Department of Chemistry, University of California, Riverside, California 92521 USA |
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| Abstract: | The tissue distribution and excretion of 14CH3S]methamidophos was followed in female Sprague-Dawley rats after intravenous injection at a toxic, but nonlethal, dose (8 mg/kg). Radiolabel was rapidly distributed to all tissues at approximately equal concentrations. Peak tissue levels were achieved within 1–10 min except in the central and peripheral nervous system where peak levels (40 nmol/g) were found between 20 and 60 min, corresponding to peak signs of toxicity. Within 24 hr of dosing, 47% of the radioactivity was recovered in the urine and 34% as 14CO2 with <5% in the feces over 7 days. Cholinesterase (ChE) inhibition was measured in erythrocytes, plasma, and various regions of the central nervous system (CNS) at selected times after administration of methamidophos at 8 mg/kg. The degree of acetylcholinesterase (AChE) inhibition in the three CNS regions was similar, reaching a minimum of 15–20% of control values at 30–60 min, when toxicity was most severe. The degree of erythrocyte AChE inhibition was less than that of the CNS although the time course was similar. Plasma ChE inhibition was more rapid than that of the CNS or erythrocytes and reactivation was slower. When similar concentrations of methamidophos to those found in vivo were incubated with CNS homogenates, plasma, or erythrocytes in vitro (5 × 10?5M) a similar degree of inhibition occurred over the same time course. It is, therefore, concluded that the cholinergic toxicity produced by methamidophos is a result of the in vivo stability of this compound combined with its entry into the nervous system in sufficiently high concentrations to inhibit AChE. |
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