Non-Invasive Biomonitoring of Pesticides

描述(申请人提供)：这项研究项目将建立一种非侵入性生物监测能力，以评估接触有机磷(OP)杀虫剂的情况，利用一种灵敏、非侵入性的微型分析仪器实时分析唾液中暴露和反应的生物标志物。该项目将创造一种对目标分析物具有高度选择性和灵敏度的微型纳米生物电子生物传感器(S)。此外，OP杀虫剂毒死蜱的生理学药代动力学和药效学模型(PBPK/PD)将被修改为包括一个唾液腺隔室，该隔室将被用来定量预测血毒死磷浓度和唾液胆碱酯酶(CHE)抑制，以基于唾液样本估计接触。利用唾液进行生物监测，结合实时监测和建模，是评价职业接触杀虫剂的一种新方法，具有广泛的应用前景。基于抗原诱导形成纳米粒子-免疫复合体纳米结构的新生物传感原理，将开发一种OP传感器。还将开发一种基于对胆碱酯酶水解反应产物胆碱和过氧化氢的电检测的胆碱酯酶传感器。随后，传感器将转化为“芯片实验室”，并对生物芯片的性能进行表征、优化和验证。为了验证这一方法，将评估不同生理条件和剂量水平下毒死蜱在唾液中的排泄和ChE抑制的药代动力学，以确保这些终点是内剂量的准确预测因子。实时唾液分析与预测药代动力学模型相结合的开发代表着相对于当前生物监测策略的重大进步。一旦这一模式系统得到充分验证，就可以很容易地用它来评估工人在各种职业情况下接触杀虫剂的情况。

DESCRIPTION (provided by applicant): This research project will establish a non-invasive biomonitoring capability to evaluate exposure to organophosphorus (OP) insecticides utilizing a sensitive, non-invasive, micro-analytical instrument for realtime analysis of biomarkers of exposure and response in saliva. This project will create a miniaturized nanobioelectronic biosensor that is highly selective and sensitive for the target analyte(s). In addition, a physiologically based pharmacokinetic and pharmacodynamic model (PBPK/PD) for the OP insecticide chlorpyrifos will be modified to incorporate a salivary gland compartment that will be used to quantitatively predict blood chlorpyrifos concentration and saliva cholinesterase (ChE) inhibition to estimate exposure based on a saliva specimen. The utilization of saliva for biomonitoring, coupled to real-time monitoring and modeling is a novel approach with broad application for evaluating occupational exposures to insecticides. An OP sensor will be developed based on a new biosensing principle of antigen-induced formation of nanoparticle-immuno complex nanostructure. A ChE sensor will also be developed based on the electrodetection of the ChE hydrolyzed reaction products choline and hydrogen peroxide. Subsequently, the sensors will be transformed to a "lab-on-a-chip", and the biochip performance will be characterized, optimized and validated. To validate this approach the pharmacokinetics of chlorpyrifos excretion and ChE inhibition in saliva under various physiological conditions and dose levels will be assessed to ensure that these endpoints are accurate predictors of internal dose. The development of a real-time saliva analysis coupled to a predictive pharmacokinetic model represents a significant advancement over current biomonitoring strategies. Once this model system has been adequately validated it can readily be employed to assess worker exposure to insecticides under a wide range of occupational situations.