Development of a magnetic immunosensor to biomonitor for the chlorpyrifos metabolite trichloropyridinol.
Liu-G; Lin-Y; Campbell-JA; Timchalk-C
Toxicologist 2007 Mar; 96(1):86-87
Biological monitoring approaches are being developed using portable analytical systems to quantify dosimetry utilizing readily obtainable body fluids (i.e. blood, urine, and saliva). To assess dosimetry to the insecticide chlorpyrifos (CPF), a fast, simple, and sensitive bioelectrochemical magnetic immunosensing method was developed to measure the metabolite trichloropyridinol (TCP). Under optimal conditions the immunosensor detected a TCP concentration as low as 6 ng L-1, which is 50-fold lower than the reported limit for a commercially available TCP ELISA assay. To establish the utility of the immunosensor, in vivo pharmacokinetic studies were conducted. Rats were given single oral gavage doses (1, 10 or 50 mg/kg) of CPF, and saliva and blood were collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and were analyzed for TCP. Trichlorpyridinol was detected in both blood and saliva at all doses and the concentration in blood exceeded saliva; although the kinetics in blood and saliva were comparable. The results from these experiments were then used to further developed a physiologically based pharmacokinetic (PBPK) model for CPF that incorporated a compartment model to describe the blood and saliva time-course of TCP. The computational model adequately simulated the results over the dose ranges evaluated. The model was further used to simulate the blood and saliva TCP concentrations for human dietary CPF exposures in the range of the Allowable Daily Intake (ADI) or Reference Dose (RfD) for CPF (0.01-0.003 mg/kg/day). The simulations suggest that the immunoassay has adequate sensitivity to detect and quantify TCP in blood and saliva at these low exposure levels. However, further studies are needed to fully understand the pharmacokinetics of CPF and TCP, particularly at low environmentally relevant doses. These initial findings suggest that the TCP immunosensor reprsents a novel approach with broad application for evaluating both occupational and environmental exposures to CPF.
Insecticides; Laboratory-animals; Animal-studies; Metabolism; Models; Pharmacodynamics; Biodynamics; Biochemical-analysis; Hemodynamics; Blood-analysis; Blood-sampling; Environmental-exposure; Occupational-exposure; Urinalysis
Agriculture, Forestry and Fishing
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina
Battelle Pacific Northwest Laboratories