ACUTE AND SUBACUTE ORGANOPHOSPHATE POISONING IN THE RAT

The intermediate syndrome in organophosphate poisoning is clinically c haracterized by weakness in the territory of cranial nerves, weakness of respiratory, neck and proximal limb muscles, and depressed deep ten don reflexes. It occurs between the acute cholinergic crisis and the u sual onset of organophosphate-induced delayed neurotoxicity. The weakn ess has been ascribed to muscle fiber necrosis. Fenthion has been the most common cause. This study assesses the occurrence of the necrotizi ng myopathy in rats in relation to the clinical course and the acetylc holinesterase (AChE) inhibition after poisoning with organophosphates representative for each of the major types of organophosphate-related neurotoxicity. Marked differences are noted in the duration of choline rgic symptoms and of AChE inhibition after either paraoxon and mipafox , or fenthion poisoning. The necrotizing myopathy begins shortly after the initial decline in AChE activity with all organophosphates studie d. Maximal muscle involvement occurs within the first 2 days of the po isoning with all organophosphates studied. The myopathy is not aggrava ted by a further decline in AChE activity in fenthion poisoning. Our d ata argues against the monophasic necrotizing myopathy being the cause of the intermediate syndrome, and is suggestive of persistent AChE in hibition being involved. (C) 1994 Intox Press, Inc.