Is oxidative stress the principal mode of toxicity for metal oxide nanoparticles?

人造纳米颗粒（NP）可以定义为人类活动有目的地产生的非常小的材料，至少有一个尺寸在1到100 nm之间（即它们比大多数化学产品大，但比生物细胞小得多）。它们目前具有巨大的科学、技术和经济重要性，在环境技术、医疗和健康应用（例如药物输送工具、诊断、抗生素）、计算、化妆品和其他方面具有广泛的应用或潜在的应用。2006年，全球研究和开发的价值约为100亿英镑，国际纳米技术市场预计在未来十年将达到数万亿美元。鉴于这种巨大的和日益增长的重要性，值得关注的是，因为（1）排放到环境中现在正在发生，并将随着纳米技术产业的增长而以越来越快的速度增长，（二）已经证明会对人类和环境健康产生重大的不利影响，但关于它们可能造成的损害类型以及这是否会在接触时导致不利的健康影响，仍然存在很大的不确定性环境中可能达到的水平。我们致力于确保负责任地开发这些非常有益的产品。这对于确保行业和政府（最终是公众）了解NP的可能风险至关重要，以便将这些风险降至最低，并防止大规模的公众反弹，例如转基因生物。金属氧化物纳米颗粒，特别是TiO 2和CeO 2，是消费品中最广泛使用的纳米颗粒之一，尽管我们缺乏在现实条件下测量浓度的方法，但几乎可以肯定这些纳米颗粒存在于环境中。有证据表明，这两种材料都可能导致生物细胞的损伤，这是由它们产生高度破坏性形式的氧（称为活性氧）的能力引起的。然而，关于这种损害是否会发生在整个生物体，特别是在淡水环境中的信息很少，而淡水环境很可能是一个主要的接触源。关于其他毒性模式是否重要的信息也很少。我们希望测试的假设，这种“氧化损伤”可以发生在淡水藻类和水蚤，大型水蚤的完整细胞。我们将使用几种最先进的分子技术（称为“组学”技术）来获得对这种氧化损伤的全面评估，以及对这些生物体中可能影响其健康的潜在替代反应（尚未确定）的评估。健康也将根据这些生物的生长和繁殖来衡量。在暴露研究之前和之后，将合成待使用的NP，并对其物理和化学特征进行充分表征，包括评估生物体的吸收情况和评估不同吸收途径的相对重要性。因此，我们将确定纳米颗粒的特定特征对环境中生物体造成的潜在损害和风险的性质和效力，从而能够开发针对性分析，以进行安全评估筛选，并提供知识，以减少对不同物种（包括人类）的风险预测的不确定性。

Manufactured nanoparticles (NPs) can be defined as very small materials purposefully produced by human activity with at least one dimension between 1 and 100 nm (i.e. they are larger than most chemical products but much smaller than biological cells). They are currently of tremendous scientific, technological and economic importance, having a wide range of applications or potential applications in environmental technologies, medical and health applications (e.g. drug delivery vehicles, diagnostics, antibiotics), computing, cosmetics and elsewhere. Global research and development was valued at approximately £10 billion in 2006 and international nanotechnology markets are expected to be valued at trillions of dollars in the next decade. Given this huge and growing importance, concern is warranted because (1) discharges into the environment are now occurring and will grow at increasing rates as the nanotechnology industry increases, (2) significant adverse effects on human and environmental health have been shown to occur and yet there remains great uncertainty as to the type of damage that they may cause and whether this can lead to adverse health effects at exposure levels likely to be achieved in the environment. We seek to ensure responsible development of these hugely beneficial products. This is vital to ensure that industry and government (and ultimately the general public) are informed of the possible risks of NPs, so that these risks can be minimised and a large scale public backlash, such as occurred for genetically modified organisms, is prevented. Metal oxide NPs, especially TiO2 and CeO2, are amongst the most widely used NPs in consumer goods and it is almost certain that these NPs are present in the environment despite our lack of methods to measure concentrations under realistic conditions. There is evidence that both of these materials can lead to damage of biological cells and that this is caused by their ability to produce highly damaging forms of oxygen (called reactive oxygen species). However, there is very little information on whether such damage can occur in whole organisms, particularly in the freshwater environment, which is likely to be a major source of exposure. There is also very little information on whether other modes of toxicity are important. We wish to test the hypothesis that such 'oxidative damage' can occur in intact cells of freshwater algae and of the water flea, Daphnia magna. We will use several state-of-the-art molecular technologies (called 'omics' techniques) to obtain a comprehensive assessment of such oxidative damage as well as an assessment of potential alternative responses (as yet unidentified) in these organisms that may impact on their health. Health will also be measured in relation to growth and reproduction of these organisms. The NPs to be used will be synthesised and well characterised in relation to physical and chemical features prior to, and after, the exposure studies, including assessments of uptake into the organisms and an assessment of the relative importance of different routes of uptake. We will thus determine the nature and potency of the potential damage and risks posed by specific characteristics of the NPs to organisms in the environment, enabling targeted analyses for safety assessment screening to be developed, and provide the knowledge to reduce uncertainty in risk prediction for different species, including humans.