Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and vehicles of administration.
Smith-JN; Campbell-JA; Busby-AL; Poet-TS; Barr-DB; Timchalk-C
Toxicologist 2009 Mar; 108(1):243
There have been numerous studies evaluating toxic and pharmacokinetic effects of the organophosphate insecticide chlorpyrifos (CPF) in which, CPF has been administered using different routes and vehicles. The objective of this study was to compare CPF pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) routes as well as corn oil, saline, and dimethyl sulfoxide (DMSO) vehicles in the rat. In the first study, CPF and isotopically labeled CPF (L-CPF) were co-administered, at doses of 5 mg/kg each, orally and IV in a saline with 5% Tween 20 vehicle. In the second study, the same doses of CPF and L-CPF were co-administered SC using corn oil and DMSO. Blood and urine samples were collected and analyzed for CPF and trichloropyridinol (TCPy). Oral CPF administration resulted in the highest peak concentration of TCPy (7-11 times higher), which also occurred most rapidly (1.5 hr prior to the next closest). SC administration with a corn oil vehicle led to faster absorption/metabolism of CPF than did SC administration using DMSO as a vehicle (ka/f: 0.6 and 0.2 mu mol/hr, respectively). IV administration of CPF caused bimodal pharmacokinetics, probably due to CPF partitioning into fat once in the body. For all exposure routes and vehicles, approximately 85% of the molar dose of CPF was excreted as some conjugated form of TCPy. Overall, orally administered CPF underwent much more extensive and rapid metabolism than did other routes investigated, probably due to first-pass metabolism. This suggests that CPF administered systemically could result in a greater body burden of CPF than would an equivalent dose administered orally, potentially leading to a higher CPF concentration at target tissues. These results will be useful for elucidating differences regarding potential uncertainty in CPF pharmacokinetics due to varying exposure routes and vehicles of administration.
Absorption-rates; Biological-effects; Biological-factors; Cell-damage; Cell-morphology; Cellular-reactions; Dose-response; Exposure-assessment; Exposure-levels; Exposure-methods; Immunology; Laboratory-animals; Molecular-biology; Organo-phosphorus-pesticides; Pesticides; Pesticides-and-agricultural-chemicals; Pharmacodynamics; Statistical-analysis; Toxic-effects; Toxins
Agriculture, Forestry and Fishing
The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
Battelle Pacific Northwest Laboratories