Toxic interaction of tetraisopropylpyrophosphoramide and propoxur: some insights into the mechanisms.

Propoxur with a non-toxic dose (5 mg/kg) administered intraperitoneally (ip) in tetraisopropylpyrophosphoramide (iso-OMPA, 1 mg/kg) pretreated rats subcutaneously, sc) produced severe intoxication of anticholinesterase nature. The observed severity was comparable to that caused by an acute sublethal dose of propoxur (15 mg/kg) suggesting at least threefold potentiation of toxicity. Either drug given alone produced neither signs of toxicity nor alterations in acetylcholinesterase (AChE) activity, while carboxylesterase (CarbE) activity was markedly reduced indicating tremendous nonspecific binding. The administration of iso-OMPA followed by propoxur elicited inhibition of AChE to a critical level and produced severe intoxication. These results suggested that iso-OMPA induced potentiation of propoxur toxicity stemmed through irreversible inhibition of CarbE.