氧化铝纳米颗粒暴露特征及其职业暴露所致神经毒性的关联性研究

项目名称： 氧化铝纳米颗粒暴露特征及其职业暴露所致神经毒性的关联性研究

项目编号： No.81472961

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张美辨

作者单位： 浙江省疾病预防控制中心

项目金额： 60万元

中文摘要： 项目旨在研究氧化铝纳米颗粒暴露特征及其颗粒聚集、生产环境因素相关的形成机制，揭示其暴露特征要素的神经毒性效应关联性。建立氧化铝纳米颗粒排放源模型，联合应用最新纳米颗粒测量技术，研究浓度演变周期性、粒径和颗粒属性的规律变化与颗粒聚集模式（原始颗粒、自身聚集或与背景颗粒结合）关系；并分析背景颗粒、作业活动、通风、空间分布和气象条件等生产环境因素对暴露特征形成的影响。基于上述两个结果建立工作场所纳米颗粒暴露评估方法。另外，从体外、动物实验研究暴露特征要素（质量浓度、数量浓度、表面积浓度、粒径和化学组成）与神经毒性指标（氧化应激、炎症反应、细胞遗传毒性、学习运动功能、神经递质等）的关联性，通过剂量效应（反应）关系筛选相应生物标志物；最后,通过人群验证来完善已建立的暴露评估方法及确认筛选出的生物标志物。研究结果将推动我国纳米颗粒职业卫生标准制定和纳米氧化铝生物标志的筛选，为纳米材料健康风险评估奠

中文关键词： 纳米颗粒；职业暴露；神经毒性；生物标志物；氧化铝

英文摘要： This project aims to study the exposure characteristics of alumina nanoparticles in the workplace and their formation mechanisms that are related to particle agglomeration and production environmental factors, as well as to reveal the association between the elements of exposure characteristics and neurotoxic effects. After a particle emission model for alumina nanoparticles is established, the relationships between particle agglomeration modes (i.e. primary particles, agglomeration or combination with background particles) and periodicity of concentration variation, dynamic change in particle size and particle nature were investigated through utilizing multiple nanoparticle measurement techniques. The influence of production environmental factors (including background particles, working activities, ventilation, spatial distribution and meteorological conditions) on exposure characteristics is investigated. The exposure assessment for nanoparticles in the workplace is established based on the above two findings. Additionally, through in vitro and in vivo tests, the correlations between the elements of exposure characteristics (e.g. mass concentration, number concentration, surface area concentration, particle size and their chemical compositions) and indicators for neurotoxic effects (e.g. oxidative stress, inflammation response, cytotoxicity and genotoxicity, functions of learning and motion, neurotransmitters) are investigated. Moreover, related biomarkers are screened through an analysis of dose-effect (response). Finally, an investigation for verification in the occupational population is conducted to improve the exposure assessment method established and to confirm the biomarkers screened. These findings will accelerate the making of occupational standards for nanoparticles in the workplace, as well as the screening of biomarkers for nano-alumina, thus provide a baseline data for the health risk assessment of nanomaterials.

英文关键词： Nanoparticle;Occupational exposure;Neurotoxicity;Biomarker;Alumina