Nanotoxicology
Nanotoxicology is the study of the toxicity of nanomaterials. Because of quantum size effects and large surface area to volume ratio, nanomaterials have unique properties compared with their larger counterparts that affect their toxicity. Of the possible hazards, inhalation exposure appears to present the most concern, with animal studies showing pulmonary effects such as inflammation, fibrosis, and carcinogenicity for some nanomaterials. Skin contact and ingestion exposure are also a concern.
Background
have at least one primary dimension of less than 100 nanometers, and often have properties different from those of their bulk components that are technologically useful. Because nanotechnology is a recent development, the health and safety effects of exposures to nanomaterials, and what levels of exposure may be acceptable, is not yet fully understood. Nanoparticles can be divided into combustion-derived nanoparticles, manufactured nanoparticles like carbon nanotubes and naturally occurring nanoparticles from volcanic eruptions, atmospheric chemistry etc. Typical nanoparticles that have been studied are titanium dioxide, alumina, zinc oxide, carbon black, carbon nanotubes, and buckminsterfullerene.Nanotoxicology is a sub-specialty of particle toxicology. Nanomaterials appear to have toxicity effects that are unusual and not seen with larger particles, and these smaller particles can pose more of a threat to the human body due to their ability to move with a much higher level of freedom while the body is designed to attack larger particles rather than those of the nanoscale. For example, even inert elements like gold become highly active at nanometer dimensions. Nanotoxicological studies are intended to determine whether and to what extent these properties may pose a threat to the environment and to human beings. Nanoparticles have much larger surface area to unit mass ratios which in some cases may lead to greater pro-inflammatory effects in, for example, lung tissue. In addition, some nanoparticles seem to be able to translocate from their site of deposition to distant sites such as the blood and the brain.
Nanoparticles can be inhaled, swallowed, absorbed through skin and deliberately or accidentally injected during medical procedures. They might be accidentally or inadvertently released from materials implanted into living tissue. One study considers release of airborne engineered nanoparticles at workplaces, and associated worker exposure from various production and handling activities, to be very probable.
Properties that affect toxicity
Size is a key factor in determining the potential toxicity of a particle. However it is not the only important factor. Other properties of nanomaterials that influence toxicity include: chemical composition, shape, surface structure, surface charge, aggregation and solubility,and the presence or absence of functional groups of other chemicals.
The large number of variables influencing toxicity means that it is difficult to generalise about health risks associated with exposure to nanomaterials – each new nanomaterial must be assessed individually and all material properties must be taken into account.
Composition
Metal-based
Metal based nanoparticles are a prominent class of NPs synthesized for their functions as semiconductors, electroluminescents, and thermoelectric materials. Biomedically, these antibacterial NPs have been utilized in drug delivery systems to access areas previously inaccessible to conventional medicine. With the recent increase in interest and development of nanotechnology, many studies have been performed to assess whether the unique characteristics of these NPs, namely their large surface area to volume ratio, might negatively impact the environment upon which they were introduced. Researchers have found that some metal and metal oxide NPs may affect cells inducing DNA breakage and oxidation, mutations, reduced cell viability, warped morphology, induced apoptosis and necrosis, and decreased proliferation. Moreover, metal nanoparticles may persist in the organisms after administration if not carefully engineered.Carbon-based
The latest toxicology studies on mice as of 2013 involving exposure to carbon nanotubes showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities. The study estimated that considerable years of exposure are necessary for significant pathology to occur.One review concludes that the evidence gathered since the discovery of fullerenes overwhelmingly points to C60 being non-toxic. As is the case for toxicity profile with any chemical modification of a structural moiety, the authors suggest that individual molecules be assessed individually.
Other
Other classes of nanomaterials include polymers such as nanocellulose, and dendrimers.Size
There are many ways that size can affect the toxicity of a nanoparticle. For example, particles of different sizes can deposit in different places in the lungs, and are cleared from the lungs at different rates. Size can also affect the particles' reactivity and the specific mechanism by which they are toxic.Dispersion state
Many nanoparticles agglomerate or aggregate when they are placed in environmental or biological fluids. The terms agglomeration and aggregation have distinct definitions according to the standards organizations ISO and ASTM, where agglomeration signifies more loosely bound particles and aggregation signifies very tightly bound or fused particles . Nanoparticles frequently agglomerate due to the high ionic strength of environmental and biological fluids, which shields the repulsion due to charges on the nanoparticles. Unfortunately, agglomeration has frequently been ignored in nanotoxicity studies, even though agglomeration would be expected to affect nanotoxicity since it changes the size, surface area, and sedimentation properties of the nanoparticles. In addition, many nanoparticles will agglomerate to some extent in the environment or in the body before they reach their target, so it is desirable to study how toxicity is affected by agglomeration.The agglomeration/deagglomeration potentials of airborne engineered nanoparticle clusters also have significant influences on their size distribution profiles at the end-point of their environmental transport routes. Different aerosolization and deagglomeration systems have been established to test stability of nanoparticle agglomerates.
Surface chemistry and charge
, in their implementation, are covered with coatings and sometimes given positive or negative charges depending upon the intended function. Studies have found that these external factors affect the degree of toxicity of NPs.Routes of administration
Respiratory
is the most common route of exposure to airborne particles in the workplace. The deposition of nanoparticles in the respiratory tract is determined by the shape and size of particles or their agglomerates, and they are deposited in the lungs to a greater extent than larger respirable particles. Based on animal studies, nanoparticles may enter the bloodstream from the lungs and translocate to other organs, including the brain. The inhalation risk is affected by the dustiness of the material, the tendency of particles to become airborne in response to a stimulus. Dust generation is affected by the particle shape, size, bulk density, and inherent electrostatic forces, and whether the nanomaterial is a dry powder or incorporated into a slurry or liquid suspension.Animal studies indicate that carbon nanotubes and carbon nanofibers can cause pulmonary effects including inflammation, granulomas, and pulmonary fibrosis, which were of similar or greater potency when compared with other known fibrogenic materials such as silica, asbestos, and ultrafine carbon black. Some studies in cells or animals have shown genotoxic or carcinogenic effects, or systemic cardiovascular effects from pulmonary exposure. Although the extent to which animal data may predict clinically significant lung effects in workers is not known, the toxicity seen in the short-term animal studies indicate a need for protective action for workers exposed to these nanomaterials. As of 2013, further research was needed in long-term animal studies and epidemiologic studies in workers. No reports of actual adverse health effects in workers using or producing these nanomaterials were known as of 2013. Titanium dioxide dust is considered a lung tumor risk, with ultrafine particles having an increased mass-based potency relative to fine TiO2, through a secondary genotoxicity mechanism that is not specific to TiO2 but primarily related to particle size and surface area.