Department of Environmental Medicine, University of Rochester, 601 Elmwood Avenue, Medical Center, Rochester, NY 14642, USA.
J Intern Med. 2010 Jan;267(1):89-105. doi: 10.1111/j.1365-2796.2009.02187.x.
Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines aimed at the betterment of human life. However, concerns have been expressed about risks posed by engineered nanomaterials (ENMs), their potential to cause undesirable effects, contaminate the environment and adversely affect susceptible parts of the population. Information about toxicity and biokinetics of nano-enabled products combined with the knowledge of unintentional human and environmental exposure or intentional delivery for medicinal purposes will be necessary to determine real or perceived risks of nanomaterials. Yet, results of toxicological studies using only extraordinarily high experimental doses have to be interpreted with caution. Key concepts of nanotoxicology are addressed, including significance of dose, dose rate, and biokinetics, which are exemplified by specific findings of ENM toxicity, and by discussing the importance of detailed physico-chemical characterization of nanoparticles, specifically surface properties. Thorough evaluation of desirable versus adverse effects is required for safe applications of ENMs, and major challenges lie ahead to answer key questions of nanotoxicology. Foremost are assessment of human and environmental exposure, and biokinetics or pharmacokinetics, identification of potential hazards, and biopersistence in cells and subcellular structures to perform meaningful risk assessments. A specific example of multiwalled carbon nanotubes (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT were found to cause asbestos-like effects of the mesothelium following intracavitary injection of high doses in rodents. The important question of whether inhaled MWCNT will translocate to sensitive mesothelial sites has not been answered yet. Even without being able to perform a quantitative risk assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics and organ toxicity, until we know better it should be made mandatory to prevent exposure by appropriate precautionary measures/regulations and practicing best industrial hygiene to avoid future horror scenarios from environmental or occupational exposures. Similarly, safety assessment for medical applications as key contribution of nanotoxicology to nanomedicine relies heavily on nano-specific toxicological concepts and findings and on a multidisciplinary collaborative approach involving material scientists, physicians and toxicologists.
纳米技术、纳米医学和纳米毒理学是互补的学科，旨在改善人类生活。然而，人们对工程纳米材料（ENMs）所带来的风险、它们造成不良影响、污染环境和对易感人群产生不利影响的潜力表示担忧。关于毒性和纳米产品的生物动力学的信息，结合对无意的人类和环境暴露或出于医疗目的的有意输送的了解，将是确定纳米材料的实际或感知风险所必需的。然而，仅使用极高实验剂量进行的毒理学研究结果必须谨慎解释。本文讨论了纳米毒理学的关键概念，包括剂量、剂量率和生物动力学的意义，并用 ENM 毒性的具体发现和讨论纳米颗粒特别是表面性质的详细理化特性表征的重要性来说明这些概念。为了安全应用 ENMs，需要对理想效果和不良反应进行彻底评估，并且纳米毒理学还面临着回答关键问题的重大挑战。首要任务是评估人类和环境暴露以及生物动力学或药代动力学，识别潜在危害，以及在细胞和亚细胞结构中的生物持久性，以进行有意义的风险评估。多壁碳纳米管（MWCNT）的具体示例说明了推断毒理学结果的困难。在啮齿动物的腔内注射高剂量后，MWCNT 被发现会引起间皮的石棉样效应。尚未回答的一个重要问题是，吸入的 MWCNT 是否会转移到敏感的间皮部位。即使由于缺乏足够的暴露、生物动力学和器官毒性数据，无法对 ENMs 进行定量风险评估，在我们了解更多情况之前，应该通过适当的预防措施/法规来防止暴露，并采取最佳的工业卫生措施，以避免未来因环境或职业暴露而出现可怕的情景。同样，作为纳米毒理学对纳米医学的主要贡献，医学应用的安全性评估在很大程度上依赖于纳米特异性毒理学概念和发现，以及涉及材料科学家、医生和毒理学家的多学科合作方法。
