INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA

唾液中铅的创新生物监测

• 批准号: 6763173
• 负责人: CHARLES TIMCHALK
• 金额: $ 24.18万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-19 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6763173
• 关键词: analytical method; biohazard detection; clearance rate; clinical chemistry; diagnosis design /evaluation; environmental exposure; excretion; laboratory rat; lead; lead poisoning; noninvasive diagnosis; pharmacokinetics; plasma; portable biomedical equipment; saliva; salivary glands; time resolved data

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.

描述（由申请人提供）：该研究项目将利用敏感的，无创的，便携式的微型分析系统来建立铅（PB）暴露的生物监测屏幕能力，以实时分析PB，该系统被排泄到唾液中。 此外，已对PB的基于生理的药代动力学模型（PBPK）进行了修改，以结合一个唾液腺室，该腔室将根据在唾液标本中检测到的PB量进行定量预测血液PB浓度和总体负担。 与实时定量和PBPK建模相结合的唾液的利用代表了一种新型方法，该方法广泛用于评估PB暴露。 为了验证这种方法，需要在各种生理条件和剂量水平下更充分了解唾液中Pb排泄的药代动力学，以确保唾液中PB的定量是“内部剂量”的准确预测指标。 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Pb的处置和清除，并在PB长时间暴露后评估唾液腺功能。 预计这些数据将对大鼠中唾液PB清除的机制提供一些了解，并将用于促进PBPK模型的进一步发展和完善，以便准确预测血液PB浓度，以及基于唾液PB的身体负担。 通过实时唾液分析的预测性药代动力学建模方法的开发代表了与当前PB生物监测筛查策略的显着进步。 可以合理地推测，一旦经过充分验证了该模型系统，就可以轻松地将其用于筛查敏感人群（例如儿童），这些人群受到慢性PB暴露的最大风险。