Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva

Abstract

There is a need to develop approaches for assessing risk associated with acute exposures to a broad range of metals and chemical agents and to rapidly determine the potential implications to human health. Noninvasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants, including heavy metals and pesticides. To advance the application of noninvasive biomonitoring a microfluidic/electrochemical device has also been developed for the analysis of lead (Pb), using square-wave anodic stripping voltametry. The system demonstrates a linear response over a broad concentration range (1–2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb acetate. Appropriate pharma-cokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for noninvasive bio-monitoring can provide a sensitive and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these noninvasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for evaluating acute exposure and health risk.

This work was partially supported by U.S. Department of Energy contract DE-AC06-76RLO1830. Although partially supported by the U.S. Environmental Protection Agency's STAR program through grant R828608, it has not been subject to any U.S. EPA review and therefore does not necessarily reflect the views of the agency, and no public endorsement should be inferred. This publication was also partially supported by grant 1 R01 OH03629-01A2 from Centers for Disease Control and prevention (CDC) and grant 1 R01 ES010976-01A2 fron the National Institute of Environmental Health Sciences (NIEHS), NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC or NIEHS.