科研与周边环境中低剂量纳米材料的长期暴露水平及其毒理学效应研究

The environmental health and safety issues of nanotechnology are highly concerned recently. However, little is known about the long-term toxicity of exposure to nanomaterials in the laboratory and surrounding environment. Graphene, a single-atom-thick sheet of graphite, is a novel nanomaterial of unique functions and structures (2010 Nobel Prize in Physics). However, the long-term toxicity upon low levels exposure of graphene is unknown. To this end, we firstly monitor the exposure of graphene-based nanomaterials during synthesis and research processes, to obtain the data of exposure levels at the laboratory and surrounding environment. Then, we will establish the methodology on quantificational assessment of the long-term toxicity under real exposure levels using Caenorhabditis elegans (C. elegans). The lifespan, reproduction, behavior, oxidative stress and thermotolerance will be tested to evaluate the long-term nanosafety. The susceptibility tests will be performed using transgenic and mutant C. elegans under both normal and stress conditions. The molecular mechanisms of the susceptiblility on graphene-based nanomaterials exposure will be elucidated. In addition to generate the fundamental knowledge on toxicity properties of graphene-based nanomaterials at the low-level and long term exposure, we also aim to find the occupational exposure limits (OELs) which will be significant for establishing a guideline for occupational protection and safety for normal and susceptible populations.

尽管纳米材料的环境健康效应已经引起学术界的高度重视，然而，针对实验室与周边环境中低剂量长期暴露的纳米材料的毒理学效应却鲜有研究，已成为亟待探索的重要前沿科学问题。单原子层厚度的石墨烯是人类目前拥有的结构和功能都最为特殊的纳米材料（2010年诺贝尔奖），其长期低剂量暴露下的毒理学效应研究尚是空白。本项目首先对石墨烯合成与研究的实验室环境中的石墨烯暴露水平进行监测和分析，确定实际暴露水平。建立定量方法，利用线虫模型定量研究低剂量长期暴露下的抗性、生长发育水平、应激能力、生殖和遗传等功能的变化。建立多种转基因及基因突变体（重点针对应激抗性基因）线虫模型，探索石墨烯暴露对体内化学生物微环境不同的易感机体产生的负面生物效应的分子机制。获得高水平原创性基础成果的同时，探索针对科研群体的暴露限量值（OELs），为国家建立相关的安全防护规范和标准提供科学依据。

本项目的研究重点是实验室与周边环境中纳米材料的释放与暴露以及低剂量暴露水平的毒理学效应研究，首先监测与评估了科研周边环境中的纳米颗粒物释放及暴露水平，建立了现场监测的标准方法与评价流程，进而为业界编著了针对现场纳米颗粒物监测的指南性书目《生产与工作场所纳米颗粒物暴露监测指南》，这些方法指南将大大促进现场监测工作的开展。同时，本项目深入研究了以石墨烯、碳纳米管、纳米银等为代表的纳米颗粒物所致毒理学效应及其作用机理；针对科研与周边现场环境中的颗粒物暴露中的实际问题，提出利用生物效应界定安全性暴露评价阈值的方法，在体内与体外水平上研究了纳米颗粒物的体内分布及诱发产生早期生物学效应指标的最低可见效应剂量，为解决周边环境暴露及安全性评价和相应的防护措施提供重要基础数据；此外，本项目建立以核分析技术为代表的纳米颗粒物研究方法，获得一系列基础性研究成果，为国家建立相关的安全防护规范和标准提供了科学依据。