INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA

描述（由申请人提供）：本研究项目将建立铅（Pb）暴露的生物监测筛选能力，利用灵敏、非侵入性、便携式微量分析系统对分泌到唾液中的Pb进行实时分析。 此外，生理为基础的药代动力学模型（PBPK）的铅已被修改，纳入唾液腺室，将被用来定量预测血液铅浓度和总的身体负担的基础上，在唾液标本中检测到的铅的量。 唾液的利用，再加上实时定量和PBPK建模代表了一种新的方法，具有广泛的应用，用于评估铅暴露。 为了验证这种方法，有必要更充分地了解铅排泄在唾液中的各种生理条件和剂量水平下的药代动力学，以确保铅在唾液中的定量是一个准确的预测“内部剂量”。 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一些了解的机制，在大鼠的唾液铅清除，并将用于促进PBPK模型的进一步发展和完善，使血液铅浓度的准确预测，并根据唾液铅的身体负担。 一个预测的药代动力学建模方法与实时唾液分析的发展代表了一个显着的进步，目前的生物监测筛选策略铅。 这是合理的推测，一旦该模型系统已得到充分验证，它可以很容易地被用来筛选敏感人群（如儿童），是最大的风险，从慢性铅暴露。

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.