Development of an integrated microanalytical system for analysis of lead in saliva and linkage to a physiologically based pharmacokinetic model describing lead saliva secretion

There is a need to develop reliable portable analytical systems for biomoni toring lead (Pb) in noninvasively collected saliva samples. In addition, ap propriate pharmacokinetic analyses are used to quantitate systemic dosimetr y based on the saliva Pb concentrations. A portable microfluidics/electroch emical device was developed for the rapid analysis of Pb based on square wa ve anodic stripping voltammetry, in which a saliva sample flows over an ele ctrode surface, Pb2+ is chemically reduced and accumulated, and the electri c potential of the electrode scanned. The system demonstrates a good linear response over a broad Pb concentration range (1-2000 ppb). To evaluate the relationship between saliva and blood Pb, rats were treated with single or al doses ranging from 20 to 500 mg Pb/kg of body weight, and 24 hours later were administered pilocarpine, a muscarinic agonist to induce salivation. To correlate saliva levels with internal dose, blood and saliva were collec ted and quantitated for Pb by inductively coupled plasma-mass spectrometry (ICP-MS) and by the microanalytical system. The quantitation with the micro analytical system was slightly less (similar to 75-85%) than with ICP-MS; h owever, the response was linear, with concentration suggesting that it can be used for the quantitation of salivary Pb. To facilitate modeling, a phys iologically based pharmacokinetic (PBPK) model for Pb was modified to incor porate a salivary gland compartment. The model was capable of predicting bl ood and saliva Pb concentration based on a limited data set. These results are encouraging, suggesting that once fully developed the microanalytical s ystem coupled with PBPK modeling can be used as important tools for real-ti me biomonitoring of Pb for both occupational and environmental exposures.