Andre Nel on Nanotechnology in Humans & the Environment
Fast Moving Front Commentary, September 2010
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Article: Toxic potential of materials at the nanolevel
Authors: Nel, A;Xia, T;Madler, L;Li,
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Andre Nel talks with ScienceWatch.com and answers a few questions about this month's Fast Moving Fronts paper in the field of Pharmacology & Toxicology.
Why do you think your paper is highly
cited?
Our paper is highly cited because it considers the interdisciplinary interactions that are needed for the safe implementation of nanotechnology in humans and the environment. Not only is the topic of nanomaterial safety of great importance to the global economy, industry, regulatory agencies, scientists, and the public at large, but it also introduces a level of complexity that requires a new level of thinking.
Our paper has contributed to the developing insight into this area because of our past experience in air pollution health effects in which knowledge of real-life exposure scenarios to small air pollution particles have led to an understanding of how nanoparticles could possibly induce disease and what investigational tools, physicochemical characterization, biological screening assays, epidemiology, exposure assessment, risk analysis, and regulatory decision-making are required for investigating and dealing with toxicological events at nanoscale level.
This approach allowed us to consider the integration of the scientific disciplines that are required to understand and make appropriate decisions about engineered nanomaterial safety. This multidisciplinary exercise has to consider materials science, chemistry, physics, biology, toxicology, occupational medicine, ecology and ecotoxicology, computer science, social science, and policy formulation.
Our review paper made an attempt to explain the role and contribution of the aforementioned disciplines in developing an integrated approach to safety considerations of nanomaterials. Moreover, based on the mechanistic insight that we have gained in studying the toxicology of ambient ultrafine particles, we were able to envisage how screening for engineered nanoparticle safety could proceed based on at least one important hazardous principle, namely, oxygen radical generation and induction of oxidative stress.
View and/or download two figures and
descriptions: "Nanomaterial Mechanisms for Oxygen Radical production"
(above), and "UC CEIN Predictive and Multi-disciplinary Toxicology
model."
Although this is only one of the potential mechanisms by which engineered nanomaterials may induce adverse health outcomes in humans and the environment, our depiction of how to implement this mechanistic concept into screening for nanomaterial hazard has provided us with one of the clearest examples to date of how to proceed in assessing nanoparticle toxicology.
Based on the importance of nanomaterial safety for the successful implementation of nanotechnology in the US and globally, our paper has continued to attract a lot of attention because of its perspective building and rational guidelines towards integrated decision-making. Recent reports about the successful implementation of toxicological research in the 21st-century by the National Academy of Sciences has confirmed the necessity of using mechanistic and high throughput paradigms as advocated in our scientific review. This report also cited the Science paper as an example of the type of future decision-making required for toxicology.
We have also been able to incorporate a lot of this thinking in the establishment of the University of California Center for the Environmental Implementations of Nanotechnology (UC CEIN) that is funded by the National Science Foundation and the Environmental Protection Agency in the US. The work in this Center is carrying out a lot of the scientific integration that is advocated in the paper.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
The paper is primarily a synthesis of knowledge and integration of multidisciplinary concepts that are needed for the safe implementation of nanotechnology, including the possible hazards that may be posed by engineered nanomaterials to humans and the environment.
In addition to the knowledge synthesis, there is also a description of the methodological approach to screening for one important aspect of nanomaterial hazard, namely the experimental observations that a variety of nanomaterials generate adverse biological effects through the catalysis of oxygen radicals and the initiation of a biological hierarchical oxidative stress response. The paper describes the different tiers of oxidative stress and how to assess them, and reviews the nanomaterial properties that could lead to the engagement of this pathway.
Would you summarize the significance of your paper
in layman's terms?
The significance of the paper is the synthesis of knowledge and an approach to the safe implementation of a powerful new technology, nanotechnology, to the benefit of humans and the environment.
The paper describes the importance of cooperation of many different scientific and societal disciplines, including nanomaterials science, chemistry, physics, biology, toxicology, occupational medicine, environmental science, and policy making, in reaching a consensus about the best approach, procedures, practices and decision-making tools for safe implementation of nanotechnology.
The paper describes this as a rational decision-making rather than the fear-driven process, which if correctly executed, should reduce concerns about the use of nanotechnology to the betterment of mankind and the environment.
How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?
The impetus of the research leading to this paper is/was the concern about the introduction of a powerful new technology, nanotechnology, which is expected to grow into a trillion-dollar industry in the next decade.
There is a lot of speculation and uncertainty about the unique properties of engineered nanomaterials and the potential that this could lead to potentially dangerous interactions at the biological level and in the environment. This includes consideration about the safety of these materials to humans and a variety of environmental life forms.
"This predictive toxicological model is further supplemented by the performance of fate and transport studies in different environmental media to understand nanomaterial exposure, bioaccumulation, and trophic transfer"
The public, scientists, government agencies, and industry called for measures that would allow the safe introduction of these materials in the setting of research laboratories, industrial production sites, worker safety, consumer products, and the likelihood that these materials will ultimately be disseminated and disposed in the environment.
At the time that this paper was written, we were at the early stages of discussing the different considerations and levels of complexity regarding the safety assessment, safety guidelines, and regulatory decision-making related to nanomaterials. Coming from a background of investigating the adverse health impacts of ambient particulate matter, Ning Li, Tian Xia, and myself were in a position to draw on our experience about the physicochemical properties of air pollution particles and how such exposure could lead to real-life toxicological and adverse health effects.
We teamed up with Dr. Lutz Mädler (Professor, Department of Production Engineering, IWT Foundation Institute of Materials Science, University of Bremen, Germany) was a visiting research exchange scholar at UCLA at the time when the paper was written. Professor Mädler is an expert in nanoparticle synthesis and was very interested in understanding how engineered nanoparticle could lead to hazard generation.
This lead to a synthesis of how our biological insight into mechanisms of air pollution adverse health effects could help to investigate the potential that novel engineered nanoparticle properties could pose a hazard at the nano-bio interface.
One of our principal observations at that time was that nanoscale ambient ultrafine particles are potentially the most dangerous particulates found in air pollution because of their small size, high rate of retention in the lung and their access to pulmonary cell type such as macrophages and epithelial cells, in which these particles generate pro-inflammatory responses. Thus, we were able to develop an understanding of how nanoparticles could lead to adverse health outcomes such as asthma and heart disease (e.g., atherosclerosis).