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Title: Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva

Abstract

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 collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and the samples were analyzed for the CPF metabolite trichlorpyridinol (TCP). Trichlorpyridinol 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 in water was 6 ng/L. 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) suggest that the electrochemical immunoassay had adequate sensitivity to detect and quantify TCP in saliva at these lowmore » exposure levels. To validate this approach further studies are needed to more fully understand the pharmacokinetics of CPF and TCP excretion in saliva. 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 insecticides.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
901177
Report Number(s):
PNWD-SA-7529
Journal ID: ISSN 0041-008X; TXAPA9; 12490; TRN: US200715%%99
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology, 219(2-3):217-225; Journal Volume: 219; Journal Issue: 2-3
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMALS; BLOOD; BODY FLUIDS; DOSIMETRY; ENVIRONMENTAL EXPOSURE; EXCRETION; IMMUNOASSAY; INSECTICIDES; KINETICS; MATHEMATICAL MODELS; METABOLITES; MONITORS; RATS; SALIVA; SENSITIVITY; WATER; chlorpyrifos, saliva, non-invasive, biomonitoring, PBPK/PD; Environmental Molecular Sciences Laboratory

Citation Formats

Timchalk, Chuck, Campbell, James A., Liu, Guodong, Lin, Yuehe, and Kousba, Ahmed A. Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva. United States: N. p., 2007. Web. doi:10.1016/j.taap.2006.10.002.
Timchalk, Chuck, Campbell, James A., Liu, Guodong, Lin, Yuehe, & Kousba, Ahmed A. Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva. United States. doi:10.1016/j.taap.2006.10.002.
Timchalk, Chuck, Campbell, James A., Liu, Guodong, Lin, Yuehe, and Kousba, Ahmed A. Thu . "Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva". United States. doi:10.1016/j.taap.2006.10.002.
@article{osti_901177,
title = {Development of a Non-Invasive Biomonitoring Approach to Determine Exposure to the Organophosphorus Insecticide Chlorpyrifos in Rat Saliva},
author = {Timchalk, Chuck and Campbell, James A. and Liu, Guodong and Lin, Yuehe and Kousba, Ahmed A.},
abstractNote = {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 collected from groups of animals (4/time-point) at 3, 6, and 12 hr post-dosing, and the samples were analyzed for the CPF metabolite trichlorpyridinol (TCP). Trichlorpyridinol 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 in water was 6 ng/L. 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) suggest that the electrochemical immunoassay had adequate sensitivity to detect and quantify TCP in saliva at these low exposure levels. To validate this approach further studies are needed to more fully understand the pharmacokinetics of CPF and TCP excretion in saliva. 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 insecticides.},
doi = {10.1016/j.taap.2006.10.002},
journal = {Toxicology and Applied Pharmacology, 219(2-3):217-225},
number = 2-3,
volume = 219,
place = {United States},
year = {Thu Mar 01 00:00:00 EST 2007},
month = {Thu Mar 01 00:00:00 EST 2007}
}