INNOVATIVE BIOMONITORING FOR LEAD IN SALIVA

唾液中铅的创新生物监测

基本信息

批准号：
7069121
负责人：
CHARLES TIMCHALK
金额：
$ 21.87万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
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/7069121
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

项目摘要

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）：该研究项目将利用灵敏、非侵入性、便携式微分析系统对排泄到唾液中的铅进行实时分析，建立铅（Pb）暴露的生物监测屏幕功能。此外，Pb 的生理学药代动力学模型 (PBPK) 已被修改，纳入唾液腺室，用于根据唾液样本中检测到的 Pb 量定量预测血液 Pb 浓度和总体负荷。唾液的利用与实时定量和 PBPK 建模相结合，代表了一种在评估铅暴露方面具有广泛应用的新方法。为了验证这种方法，需要更全面地了解不同生理条件和剂量水平下唾液中 Pb 排泄的药代动力学，以确保唾液中 Pb 的定量能够准确预测“内部剂量”。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，并评估长期接触铅后的唾液腺功能。预计这些数据将为大鼠唾液 Pb 清除机制提供一定的了解，并将用于促进 PBPK 模型的进一步开发和完善，从而能够根据唾液准确预测血液 Pb 浓度和身体负荷铅。与实时唾液分析相结合的预测药代动力学模型方法的开发代表了当前 Pb 生物监测筛查策略的重大进步。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查长期接触铅风险最大的敏感人群（例如儿童）。