From Airborne Exposures to Biological Effects (FABLE): the impact of nanoparticles on health

纳米颗粒(NPs--尺寸小于十亿分之一米的非常小的颗粒)正越来越多地被用于各种商品的制造和其他有益用途。它们也存在于车辆和工业废气中，但我们对它们危害健康的能力知之甚少。虽然有办法根据现有水平及其已知的生物影响对环境中的化学品进行风险评估，但现有信息不足，无法对核燃料进行风险评估。这项工作将涉及Defra最近确定的与核动力源以及人类和环境健康有关的近四分之三的优先目标，从而将使核动力源风险评估发生重大变化。要做到这一点，需要具有不同类型的技能和知识(从化学、物理、分子和细胞生物学、毒理学、暴露测量、材料科学和健康/医学)的科学家合作，共同采取一种方法，了解人类接触NPs的程度及其对身体的影响。在这个项目中，我们将测量城市和农村室外、室内以及个人暴露水平。我们将集中于三种金属(铈、锌和钒)，因为它们存在于汽车尾气中。我们将在一系列实验室实验中使用这些现实生活中的水平(而不是通常使用高浓度的方法)来定义这些NPs一旦吸入就会去哪里，以及它们可能造成的损害。我们将在实验室测试中找出这些金属纳米颗粒(它们具有不同的形状、大小和化学组成)是如何进入细胞的。我们还将在实验室中研究来自人类肺和鼻子内部的细胞，一旦这些NPs进入这些细胞，它们是如何移动的。由于哮喘患者可能更容易受到这些影响的影响，我们也将研究哮喘患者的细胞。NP能够进入神经细胞，由于这可能使它们进入大脑，我们还将研究这一可能的进入途径。一旦NPs进入细胞，它们就会造成伤害，我们将利用最先进的技术研究，一旦这些NPs进入细胞，哪些分子会被刺激出现。这将告诉我们可能发生的过程(例如炎症)，从而使我们能够确定可能的“安全”暴露水平。然后，我们将能够通过与健康和安全执行部以及环境、食品和农村事务部(Defra)的互动，就NPs的安全开发和使用提供建议，后者负责监管英国的NPs。

Lay summary Nanoparticles (NPs - very small particles less than 1 hundred millionth of a meter in size) are increasingly being used in the manufacture of a wide range of goods and for other beneficial uses. They are also found in vehicle and industrial emissions and yet we know little about their capability to harm health. Although there are ways to achieve a risk assessment for chemicals in the environment based on the levels that exist and their known biological effects, there is insufficient information available to allow a risk assessment of NPs. This work will address almost three quarters of the priority objectives recently set by Defra in relation to NPs and human and environmental health and thus will make a major step-change in the assessment of risks from NPs. To do this requires the collaboration of scientists with different types of skills and knowledge (ranging from chemistry, physics, molecular and cellular biology, toxicology, exposure measurement, materials science and health/medicine ) to join forces in an approach to understand the extent of human exposures to NPs and how they affect the body. In this project, we will measure levels of NPs outdoors in urban and rural locations, indoors and also personal levels of exposure. We will concentrate on 3 metals (cerium, zinc and vanadium) as these are found in vehicle exhaust. We will use these real life levels (rather than the usual approach of using high concentrations) in a series of lab experiments to define where these NPs go once breathed in and what damage they might do. We will work out how these metal NPs (which have different shapes, sizes and chemical make up) find their way into cells in laboratory tests. We will also work out in cells from the human lung and the inside of the nose in the laboratory how these NPs move once they have got inside these cells. As asthmatic subjects may be more susceptible to these effects we will also look at cells from asthma patients. NPs are able to get inside nerve cells and as this may allow them to get to the brain, we will also look at how this possible route of entry. Once NPs have entered cells they are in a position to cause harm and we will study, using state of the art technology, which molecules are stimulated to appear once these NPs have entered the cells. This will tell us what sorts of processes might occur (e.g. inflammation) and consequently will allow us to establish possible 'safe' levels of exposure. We will then be able to advise on the safe development and use of NPs through interaction with the Health and Safety Executive and the Department of Environment, Food and Rural Affairs (Defra) who are responsible for the regulation of NPs in the UK.