PNNL

Abstract

There have been numerous studies evaluating toxic and pharmacokinetic effects of the organophosphorus insecticide chlorpyrifos (CPF); in which, CPF has been administered using different exposure routes and administration vehicles. The objective of this study was to compare CPF pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co-administered equal doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF). One group was exposed by both oral and IV routes using saline/Tween 20 vehicle; whereas, the second group was exposed by the SC route using two vehicles, corn oil and DMSO. A third group was only administered CPF by the oral route in corn oil. For all treatments, blood and urine time course samples were collected and analyzed for trichloropyridinol (TCPy), and isotopically labeled trichloropyridinol (L-TCPy). Peak TCPy concentrations in blood (>78%), TCPy blood AUC (>16%), and percent of dose excreted in urine (100%) were all highest in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly obtained after oral administration of CPF in saline Tween 20 (>1.5 h).