Toxicokinetics of parathion and paraoxon in rainbow trout after intravascular administration and water exposure.
Fish are less sensitive than mammals to organophosphate insecticide toxicity. The species differences have been mainly investigated by biochemical studies of AChE and organophosphate interaction. To examine whether species differences in the toxicokinetics of the organophosphate insecticides were also involved in their differential toxicity, rainbow trout were fitted with a dorsal aorta cannula and administered parathion and its active metabolite paraoxon intraarterially (ia) and via water exposure. Serial blood samples were removed and the plasma concentrations of parathion and paraoxon were determined by capillary GC with EC detection. Plasma protein binding was determined by equilibrium dialysis and ultrafiltration. After ia injection the plasma concentration-time profiles of parathion and paraoxon were multiexponential, with a terminal t1/2 of 56.1 and 0.528 hr. The steady-state volumes of distribution and total body clearances (CLb) for parathion and paraoxon were 1370 and 1080 ml kg-1 and 21.4 and 3020 ml hr-1 kg-1; the plasma unbound fractions were 1.23 and 52.5%. The large difference in CLb between parathion and paraoxon appeared to result primarily from differences in plasma protein binding. Parathion had greater persistence in trout than rat, suggesting that sensitivity difference were unrelated to toxicokinetic differences.
Abbas
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Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Ohio State University, Columbus 43210, USA.
Schultz
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IR
Doddapaneni
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Hayton
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WL
D000818:Animals; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002849:Chromatography, Gas; D004781:Environmental Exposure; D005260:Female; D005618:Fresh Water / Q000032:analysis; D007269:Injections, Intra-Arterial; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D017686:Oncorhynchus mykiss; D010261:Paraoxon / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010278:Parathion / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D014873:Water Pollutants / Q000633:toxicity
D001798:Blood Proteins; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D014873:Water Pollutants; D010278:Parathion; D010261:Paraoxon