This research project will establish a biomonitoring screen capability for lead (Pb) exposure utilizing a sensitive, non-invasive, portable micro-analytical system for real-time analysis of Pb that is excreted into saliva. In addition, a physiologically based pharmacokinetic model (PBPK) for Pb has been modified to incorporate a salivary gland compartment that will be utilized to quantitatively predict blood Pb concentration and total body burden based on the amount of Pb detected in saliva specimens. The utilization of saliva, coupled to real-time quantitation and PBPK modeling represents a novel approach having broad application for evaluating Pb exposures. In order to validate this approach there is a need to more fully understand the pharmacokinetics of Pb excretion in saliva under various physiological conditions and dose levels to ensure that the quantitation of Pb in saliva is an accurate predictor of """"""""internal dose"""""""". To accomplish this goal a series of in vitro and in vivo studies will be conducted to evaluate the disposition and clearance of Pb in the blood, plasma, and saliva, and to evaluate salivary gland function following a prolonged Pb exposure. It is anticipated that these data will provide some understanding of the mechanism for saliva Pb clearance in the rat, and will be used to facilitate further development and refinement of the PBPK model to enable accurate prediction of blood Pb concentration, and body burden based on saliva Pb. The development of a predictive pharmacokinetic modeling approach with real-time saliva analysis represents a significant advancement over current biomonitoring screening strategies for Pb. It is reasonable to speculate that once this model system has been adequately validated it can readily be employed to screen sensitive populations (e.g. children) that are at greatest risk from chronic Pb exposure.
