In articulating a vision for Toxicity Testing in the 21st Century, the National Research Council (NRC) noted that exposure science will play a critical role. In this context, biomonitoring is a key component that quantitatively associates an internal dose with a measurable effect. It has also been suggested that epidemiology studies which accurately assess chemical exposures along with biological effects will have the most meaningful interpretation and thus maximal impact. A major impediment for conducting biomonitoring within epidemiology studies is the lack of rapid, field deployable, quantitative technologies that measure chemical exposures using minimally invasive biological fluids, such as saliva. Our recently completed research resulted in the development of pesticide sensor platforms, an in vivo animal model system for rapid characterization of saliva pesticide uptake and clearance, and a dosimetry model to predict systemic dose based upon a 'spot'saliva measurement. Recently, the utility of the sensor was confirmed by measuring a target analyte in saliva from pesticide manufacturing plant workers. This project has been highly successful and can be utilized as a framework for evaluating a broader range of important chemicals. Since human exposure is rarely to single agents but rather to complex mixtures, there is a need to develop biomonitoring strategies capable of measuring multiple analytes. This is particularly true in agriculture where multiple pesticides are routinely utilized on crops. Clearly there is a need t extend the strategy to other important pesticides;however, a major limitation is the inability to priori identify which chemicals are readily cleared in saliva, hampering our ability to easily develop a multiplex screening platform. To address this challenge, it is hypothesized that chemical uptake and clearance in saliva can readily be predicted for a broad range of chemicals based upon limited in vitro experiments which are integrated into a pharmacokinetic model. To test this hypothesis this continuation project will exploit the previously developed in vivo rat model for salivary gland uptake and clearance and will develop additional in vitro cell and sub-cellular based approaches for a broad range of pesticides having differing physical and chemical characteristics as well as clearance mechanisms. Once validated, this approach can guide sensor platform development since model simulations will provide critical information on detection limits and clearance rates.
This research project will specifically focus on the development of a novel chemical screening strategy to enable subsequent rapid development of a multiplex sensor array platform for quantification of multiple pesticides in saliva. This novel platform will enable a more accurate prediction of exposures and once validated, can readily be employed to assess dosimetry to pesticide mixtures in support of biomonitoring and epidemiology studies.
|Waters, Katrina M; Cummings, Brian S; Shankaran, Harish et al. (2014) ERK oscillation-dependent gene expression patterns and deregulation by stress response. Chem Res Toxicol 27:1496-503|
|Zhang, Weiying; Tang, Yong; Du, Dan et al. (2013) Direct analysis of trichloropyridinol in human saliva using an Au nanoparticles-based immunochromatographic test strip for biomonitoring of exposure to chlorpyrifos. Talanta 114:261-7|
|Du, Dan; Wang, Jun; Wang, Limin et al. (2011) Magnetic electrochemical sensing platform for biomonitoring of exposure to organophosphorus pesticides and nerve agents based on simultaneous measurement of total enzyme amount and enzyme activity. Anal Chem 83:3770-7|
|Wang, Limin; Lu, Donglai; Wang, Jun et al. (2011) A novel immunochromatographic electrochemical biosensor for highly sensitive and selective detection of trichloropyridinol, a biomarker of exposure to chlorpyrifos. Biosens Bioelectron 26:2835-40|
|Zou, Zhexiang; Du, Dan; Wang, Jun et al. (2010) Quantum dot-based immunochromatographic fluorescent biosensor for biomonitoring trichloropyridinol, a biomarker of exposure to chlorpyrifos. Anal Chem 82:5125-33|
|Smith, Jordan N; Wang, Jun; Lin, Yuehe et al. (2010) Pharmacokinetics of the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCPy) in rat saliva. Toxicol Sci 113:315-25|
|Busby-Hjerpe, Andrea L; Campbell, James A; Smith, Jordan Ned et al. (2010) Comparative pharmacokinetics of chlorpyrifos versus its major metabolites following oral administration in the rat. Toxicology 268:55-63|
|Barry, Richard C; Lin, Yuehe; Wang, Jun et al. (2009) Nanotechnology-based electrochemical sensors for biomonitoring chemical exposures. J Expo Sci Environ Epidemiol 19:1-18|
|Garabrant, David H; Aylward, Lesa L; Berent, Stanley et al. (2009) Cholinesterase inhibition in chlorpyrifos workers: Characterization of biomarkers of exposure and response in relation to urinary TCPy. J Expo Sci Environ Epidemiol 19:634-42|
|Du, Dan; Wang, Jun; Smith, Jordan N et al. (2009) Biomonitoring of organophosphorus agent exposure by reactivation of cholinesterase enzyme based on carbon nanotube-enhanced flow-injection amperometric detection. Anal Chem 81:9314-20|
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