title: Development of a non-invasive biomonitoring approach to determine exposure to the organophosphorus insecticide chlorpyrifos in rat saliva.
abstract: Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantify dosimetry utilizing readily obtainable body fluids, such as saliva. In the current study, rats were given single oral gavage doses (1, 10, or 50 mg/kg) of the insecticide chlorpyrifos (CPF). Saliva and blood were then collected from groups of animals (4/time-point) at 3, 6, and 12 h post-dosing, and were analyzed for the CPF metabolite trichloropyridinol (TCP). Trichloropyridinol was detected in both blood and saliva at all doses and the TCP concentration in blood exceeded saliva, although the kinetics in blood and saliva were comparable. A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF incorporated a compartment model to describe the time-course of TCP in blood and saliva. The model adequately simulated the experimental results over the dose ranges evaluated. A rapid and sensitive sequential injection (SI) electrochemical immunoassay was developed to monitor TCP, and the reported detection limit for TCP was 6 ng/L (in water). Computer model simulation in the range of the Allowable Daily Intake (ADI) or Reference Dose (RfD) for CPF (0.01-0.003 mg/kg/day) suggests that the electrochemical immunoassay has adequate sensitivity to detect and quantify TCP in saliva at these low exposure levels. However, to validate this approach, further studies are needed to more fully understand the pharmacokinetics of CPF and TCP excretion in saliva. These initial findings suggest that the utilization of saliva as a biomonitoring matrix, coupled to real-time quantitation and PBPK/PD modeling represents a novel approach with broad application for evaluating both occupational and environmental exposures to CPF.
authors.affiliation: Pacific Northwest National Laboratory, 902 Battelle, Blvd., Richland, WA 99352, USA. charles.timchalk@pnl.gov
authors.forename: Charles
authors.initials: C
authors.lastname: Timchalk
authors.forename: James A
authors.initials: JA
authors.lastname: Campbell
authors.forename: Guodong
authors.initials: G
authors.lastname: Liu
authors.forename: Yuehe
authors.initials: Y
authors.lastname: Lin
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Kousba
mesh_terms: D000818:Animals; D004390:Chlorpyrifos / Q000032:analysis* / Q000493:pharmacokinetics; D004784:Environmental Monitoring / Q000379:methods*; D007306:Insecticides / Q000032:analysis* / Q000493:pharmacokinetics; D008297:Male; D008954:Models, Biological; D011728:Pyridones / Q000032:analysis* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000378:metabolism*
chemical_list: D007306:Insecticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D004390:Chlorpyrifos