Studies on the mechanism of toxicity of the organophosphorus pesticide triamiphos

Abstract

The i.p. LD_{5 0} of the organophosphorus ester triamiphos to adult male rat is about 15 mg/kg. The symptoms are typical of peripheral cholinesterase inhibition. Thus death is due to respiratory paralysis; there is no stimulation of the central nervous system. Measurement of the cholinesterase activity of several tissues after i.p. administration of various doses of triamiphos indicates that: (1) the rapidity of true cholinesterase inhibition at the myoneural junction is a major factor in the outcome of the acute intoxication; (2) brain true cholinesterase is not significantly inhibited; (3) in vivo, pseudocholinesterase is more inhibited than true cholinesterase; (4) except in the intestine, no return of cholinesterase activity was observed within 18 hr following the injection. Triamiphos is not a direct cholinesterase inhibitor but conversion by the liver to an anticholinesterase agent has been demonstrated by incubation of triamiphos with a fortified liver preparation. The active metabolite is very labile and does not readily cross the blood brain-barrier.