INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA

描述(申请人提供)：该研究项目将建立铅暴露的生物监测筛查能力，利用灵敏、非侵入性、便携式微型分析系统实时分析排出到唾液中的铅。此外，基于生理的铅的药代动力学模型(PBPK)已经被修改为包括一个唾液腺隔室，该隔室将被用于根据唾液样本中检测到的铅量来定量预测血铅浓度和全身负荷。唾液的利用，结合实时定量和PBPK模型，代表了一种在评估铅暴露方面具有广泛应用的新方法。为了验证这一方法，有必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一个准确的内剂量预测因子。为了实现这一目标，将进行一系列的体外和体内研究，以评估铅在血液、血浆和唾液中的处置和清除，并评估长期铅暴露后的唾液腺功能。预计这些数据将提供对大鼠唾液铅清除机制的一些了解，并将被用于促进PBPK模型的进一步发展和改进，以实现基于唾液铅的血铅浓度和身体负荷的准确预测。具有实时唾液分析的预测性药代动力学建模方法的发展代表着相对于当前的铅生物监测筛选策略的重大进步。有理由推测，一旦这个模型系统得到充分验证，它就可以很容易地用于筛查长期铅暴露风险最大的敏感人群(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.