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Posted: Sep 13th, 2007
Nanotechnology risks - where are we today?
(Nanowerk Spotlight) New technology, whether it is a novel cancer treatment or an innovative approach to making a new material, almost always comes with risk. Nanotechnologies are no different. Certain nano-fabrication techniques employ toxic chemicals, the production of carbon nanotubes results in dangerous byproducts, and the big question as to what degree certain engineered nanoparticles could be harmful to humans and the environment has not been answered yet. The potentially adverse health effects of fine and ultrafine particles have been studied for decades. However, at the core of the nanotoxicological debate is the fact that nanoparticles are not just a smaller version of certain particles, but they are very different from their everyday counterparts with regard to their physical properties and catalytic activities. Thus their adverse effects cannot simply be derived from the known toxicity of the macro-sized material. One useful contribution to moving the nanotoxicology discussion further along came from the 1st Nobel Forum Mini-Symposium on Nanotoxicology that was held in Stockholm, Sweden. The event's program was devoted to the topic of definitions and standardization in nanotoxicological research, as well as nano-specific risk assessment and regulatory/legislative issues. A group of international experts presented examples of recent and ongoing studies of carbon-based nanomaterials, including single-walled carbon nanotubes, using a wide range of in vitro and in vivo model systems. This Spotlight will provide you with some highlights and conclusions from this exciting meeting.
Borrowing from Feynman's famous 1959 speech There is Plenty of Room at the Bottom, the event organizers chose the title There’s Plenty of Room at the Forum for their discourse, intended to emphasize the fact that there is plenty of opportunity not only for discussion, but also for actual collaboration in the emerging and important area of nanotoxicology.
"Indeed, we need to recognize that it is essential for the international community of nanotoxicologists to coordinate its efforts in order to avoid duplication, and also to enable us to cover a wider area of research, which is important because the nanotechnologies are developing at a very rapid pace" Dr. Bengt Fadeel tells Nanowerk.
"We as toxicologists and risk assessment experts need to discuss in detail and in the spirit of pre-competitive cooperation how to reach the goal of safe handling of
the nanotechnologies" writes Fadeel.
The researchers at the symposium pointed out that we are currently witnessing only the first generation of engineered nanomaterials, while more sophisticated nanomaterials
and nanodevices are waiting around the corner.
"We feel that it is of utmost importance to develop strategies and methodologies that will allow us to predict and respond to the potential hazardous effects not only of existing (passive) nanomaterials but also of active nanostructures and integrated nanosystems that may gradually approach the dimensions and the enormous complexities of biological systems" the authors write. "While we cannot predict the future, we need to prepare for it. Towards that aim, we believe that a proportion of the global funding of nanotechnology-related activities should be devoted to nanotoxicological research and risk assessment, which should be conducted on an interdisciplinary and intercontinental level."
Fadeel's review covers five major areas which e have excerpted and summarized for you below:
Materials and methods: The importance of standardization
Standardization, in the context related to technologies
and industries, is the process of establishing
a technical standard among competing entities in a
market, where this will bring benefits without hurting
competition. International activities in the area
of nanotechnologies are coordinated by the International
Standards Organization (ISO) which established
the ISO Technical Committee in 2005.
While a unified procedure to classify all
nanomaterials and their applications seems unlikely,
there is nevertheless an urgent need for answering
some outstanding questions especially in connection
to the biological effects of novel nanomaterials and
the possible health and environmental problems they
may cause. The two most obvious requirements
concern the comparability of the methods used for
monitoring of adverse effects and the materials that
are subject to such investigations. Therefore, there is
a need for standardized toxicological assays as well as
reference materials to classify the measured effects
and compare them with those from other laboratories
in other countries.
Not only the materials but also the methods should be standardized and validated. Recent studies demonstrate that results obtained with specific assays for toxicity may have been invalidated by the presence of investigated nanoparticles leading to false-positive outcomes.
Human studies of engineered nanoparticles: A comparison with air pollution
Conventional health-related aerosol exposure measurements performed on the basis of the mass of particles per unit volume of air may not be applicable to airborne nanoparticles, since certain respirable nanometer sized particles may be more toxic than larger particles with a similar composition . New methodologies and instruments for exposure measurements are therefore needed in order to provide detailed information on the nature of airborne engineered nanoparticles to which humans are exposed.
The mechanisms underlying adverse health effects of air pollution are largely unknown, but autonomic regulation of the heartbeat, inflammation and systemic coagulation effects, and direct metal toxicity to the myocardium have been proposed.
The researchers conclude that
the hypothesis that systemic access of ultrafine insoluble particles may induce adverse reactions in the cardiovascular
system, and other organs, leading to the onset of cardiovascular disease in human subjects, requires careful consideration. Moreover, other, not generally
recognized routes of exposure to engineered nanomaterials, including the putative uptake of inhaled nanoparticles into the brain via the olfactory nerve also need
to be considered, although the relevance of such clearance pathways for human exposure remains to be established.
Single-walled carbon nanotubes: Understanding and controlling their toxicity
Carbon nanotubes (CNTs) are some of the most researched nanoparticles. Their increasing use in industry has prompted a number of toxicology studies. The participants at the symposium discussed numerous studies that deal with some form of human health and biocompatibility of CNTs, especially single-walled CNTs. It appears that researchers are far from being able to reach conclusive positions on these issues. It was pointed out, though, that there are indications that functionalization of CNTs may serve to minimize adverse biological effects related to unwanted tissue accumulation.
Risk assessment of engineered nanomaterials: The importance of surface area
Paracelsus (1493 – 1541), widely regarded as the father of toxicology, formulated the expression, ‘All things are poison and nothing is without poison’, suggesting that ‘dose determines the poison’. In the field of nanotoxicology, the critical question is which particle characteristics are central in initiating and perpetuating the adverse effects? For instance, will surface area serve as a better determinant of nanoparticle toxicity than mass, as suggested by pioneering animal studies of particle deposition and retention in the lung? Indeed, the greater surface area per mass compared with larger-sized particles of the same composition renders nanomaterials more biologically reactive. The answers to these questions have profound implications for risk assessment of the hazardous effects of engineered nanomaterials.
The researchers pointed out that there is a strong likelihood that the biological activity of nanoparticles will depend on physico-chemical parameters not routinely considered in toxicity screening studies. One consequence of this would be that the regulation of human occupational exposures, which is currently based on airborne mass concentration, need to be reconsidered in light of these findings.
Regulation of the nanotechnologies: Identifying knowledge gaps
Several important ‘knowledge gaps’ were identified
and discussed at the Nobel Forum minisymposium,
and efforts to address these issues will
be required to ensure science-based decision making
and implementation of existing legislations: (i)
nomenclature, definitions, and standards; (ii) hazard
characterization; (iii) exposure and effects assessment;
(iv) environmental fate, transport, and persistence;
and (v) measurement, sampling, and
monitoring of nanomaterials. The central challenge
from a regulatory point of view is, of course, how to
protect public interest (health, safety, privacy, environment,
etc) without hampering technological
progress. This can only be accomplished through a
close dialogue between researchers and legislators to
identify central issues to be tackled from both a
scientific and a regulatory perspective.