INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA

描述（由申请人提供）：该研究项目将利用灵敏、无创、便携式微分析系统建立铅暴露的生物监测屏幕能力，实时分析排泄到唾液中的铅。此外，对基于生理的铅药代动力学模型（PBPK）进行了改进，将唾液腺室纳入其中，该模型将用于根据唾液标本中检测到的铅量定量预测血铅浓度和全身负荷。利用唾液，结合实时定量和PBPK建模，代表了一种具有广泛应用价值的评估铅暴露的新方法。为了验证这一方法，需要更全面地了解不同生理条件和剂量水平下唾液中铅排泄的药代动力学，以确保唾液中铅的定量是“内剂量”的准确预测因子。为了实现这一目标，将进行一系列体外和体内研究，以评估血液、血浆和唾液中铅的处置和清除，并评估长期铅暴露后唾液腺的功能。预计这些数据将有助于了解大鼠唾液中铅清除的机制，并将用于进一步开发和完善PBPK模型，以准确预测血铅浓度和基于唾液铅的身体负荷。基于实时唾液分析的预测药代动力学建模方法的发展代表了当前生物监测Pb筛选策略的重大进步。有理由推测，一旦该模型系统得到充分验证，它就可以很容易地用于筛选慢性铅暴露风险最大的敏感人群（例如儿童）。

DESCRIPTION (provided by applicant): 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.