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Nanotoxicology is the study of the
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
of
nanomaterials * Nanomaterials describe, in principle, materials of which a single unit is sized (in at least one dimension) between 1 and 100 nm (the usual definition of nanoscale). Nanomaterials research takes a materials science-based approach to n ...
. 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 Inhalation is a major route of exposure that occurs when an individual breathes in polluted air which enters the respiratory tract. Identification of the pollutant uptake by the respiratory system can determine how the resulting exposure contrib ...
appears to present the most concern, with
animal studies Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including geography, art history, ant ...
showing pulmonary effects such as
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
,
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
, and
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
icity for some nanomaterials. Skin contact and ingestion exposure are also a concern.


Background

Nanomaterials * Nanomaterials describe, in principle, materials of which a single unit is sized (in at least one dimension) between 1 and 100 nm (the usual definition of nanoscale). Nanomaterials research takes a materials science-based approach to n ...
have at least one primary dimension of less than 100
nanometers 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
, and often have properties different from those of their bulk components that are technologically useful. Because
nanotechnology Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal ...
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 (like diesel soot), manufactured nanoparticles like carbon nanotubes and naturally occurring nanoparticles from volcanic eruptions, atmospheric chemistry etc. Typical nanoparticles that have been studied are
titanium dioxide Titanium dioxide, also known as titanium(IV) oxide or titania , is the inorganic compound with the chemical formula . When used as a pigment, it is called titanium white, Pigment White 6 (PW6), or CI 77891. It is a white solid that is insolu ...
, alumina, zinc oxide,
carbon black Carbon black (subtypes are acetylene black, channel black, furnace black, lamp black and thermal black) is a material produced by the incomplete combustion of coal and coal tar, vegetable matter, or petroleum products, including fuel oil, fluid ...
,
carbon nanotube A scanning tunneling microscopy image of a single-walled carbon nanotube Rotating single-walled zigzag carbon nanotube A carbon nanotube (CNT) is a tube made of carbon with diameters typically measured in nanometers. ''Single-wall carbon na ...
s, and
buckminsterfullerene Buckminsterfullerene is a type of fullerene with the formula C60. It has a cage-like fused-ring structure (truncated icosahedron) made of twenty hexagons and twelve pentagons, and resembles a soccer ball. Each of its 60 carbon atoms is bonded ...
. 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 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re, ...
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 group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the r ...
s 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
nanoparticle A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 10 ...
s (NPs) are a prominent class of NPs synthesized for their functions as
semiconductor A semiconductor is a material which has an electrical conductivity value falling between that of a conductor, such as copper, and an insulator, such as glass. Its resistivity falls as its temperature rises; metals behave in the opposite way ...
s, electroluminescents, and
thermoelectric materials Thermoelectric materials show the thermoelectric effect in a strong or convenient form. The ''thermoelectric effect'' refers to phenomena by which either a temperature difference creates an electric potential or an electric current creates a t ...
. Biomedically, these
antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
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 Nanotechnology, also shortened to nanotech, is the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes. The earliest, widespread description of nanotechnology referred to the particular technological goal ...
, 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 Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
and
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...
, 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 A scanning tunneling microscopy image of a single-walled carbon nanotube Rotating single-walled zigzag carbon nanotube A carbon nanotube (CNT) is a tube made of carbon with diameters typically measured in nanometers. ''Single-wall carbon na ...
(CNT) showed a limited pulmonary inflammatory potential of
MWCNT A scanning tunneling microscopy image of a single-walled carbon nanotube Rotating single-walled zigzag carbon nanotube A carbon nanotube (CNT) is a tube made of carbon with diameters typically measured in nanometers. ''Single-wall carbon na ...
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 Nanocellulose is a term referring to nano-structured cellulose. This may be either cellulose nanocrystal (CNC or NCC), cellulose nanofibers (CNF) also called nanofibrillated cellulose (NFC), or bacterial nanocellulose, which refers to nano-struc ...
, and
dendrimer Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The ...
s.


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 (typically occurring during synthesis or drying). 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 (mechanical stability) 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

NPs NPS may refer to: Organizations * National Park Service, U.S. * National Pension System, India * National Pension Service, Korea * National Phobics Society, UK charity * National Piers Society, UK charity * National Poetry Slam, competition * N ...
, 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

Inhalation exposure Inhalation is a major route of exposure that occurs when an individual breathes in polluted air which enters the respiratory tract. Identification of the pollutant uptake by the respiratory system can determine how the resulting exposure contrib ...
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 Animal studies is a recently recognised field in which animals are studied in a variety of cross-disciplinary ways. Scholars who engage in animal studies may be formally trained in a number of diverse fields, including geography, art history, ant ...
, nanoparticles may enter the bloodstream from the lungs and translocate to other organs, including the brain. The inhalation risk is affected by the
dustiness Dustiness is the tendency of particles to become airborne in response to a mechanical or aerodynamic stimulus. Dustiness is affected by the particle shape, size, and inherent electrostatic forces. Dustiness increases the risk of inhalation exposur ...
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 A slurry is a mixture of denser solids suspended in liquid, usually water. The most common use of slurry is as a means of transporting solids or separating minerals, the liquid being a carrier that is pumped on a device such as a centrifugal p ...
or liquid
suspension Suspension or suspended may refer to: Science and engineering * Suspension (topology), in mathematics * Suspension (dynamical systems), in mathematics * Suspension of a ring, in mathematics * Suspension (chemistry), small solid particles suspende ...
. Animal studies indicate that
carbon nanotube A scanning tunneling microscopy image of a single-walled carbon nanotube Rotating single-walled zigzag carbon nanotube A carbon nanotube (CNT) is a tube made of carbon with diameters typically measured in nanometers. ''Single-wall carbon na ...
s and
carbon nanofiber Carbon nanofibers (CNFs), vapor grown carbon fibers (VGCFs), or vapor grown carbon nanofibers (VGCNFs) are cylindrical nanostructures with graphene layers arranged as stacked cone (geometry), cones, cups or plates. Carbon nanofibers with graphene ...
s can cause pulmonary effects including
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
,
granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious o ...
s, and
pulmonary fibrosis Pulmonary fibrosis is a condition in which the lungs become scarred over time. Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. Complications may include pulmonary hypertension, respiratory failu ...
, which were of similar or greater potency when compared with other known
fibrogenic Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perman ...
materials such as
silica Silicon dioxide, also known as silica, is an oxide of silicon with the chemical formula , most commonly found in nature as quartz and in various living organisms. In many parts of the world, silica is the major constituent of sand. Silica is ...
,
asbestos Asbestos () is a naturally occurring fibrous silicate mineral. There are six types, all of which are composed of long and thin fibrous crystals, each fibre being composed of many microscopic "fibrils" that can be released into the atmosphere b ...
, and ultrafine
carbon black Carbon black (subtypes are acetylene black, channel black, furnace black, lamp black and thermal black) is a material produced by the incomplete combustion of coal and coal tar, vegetable matter, or petroleum products, including fuel oil, fluid ...
. Some studies in cells or animals have shown
genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic s ...
or
carcinogen A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive sub ...
ic effects, or systemic
cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
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 Titanium dioxide, also known as titanium(IV) oxide or titania , is the inorganic compound with the chemical formula . When used as a pigment, it is called titanium white, Pigment White 6 (PW6), or CI 77891. It is a white solid that is insolu ...
(TiO2) dust is considered a
lung tumor Lung tumors are neoplastic lung nodules. These include: Primary tumors of the lung/pulmonary system: * Bronchial leiomyoma, a rare, benign tumor * Lung cancer, the term commonly used to refer to ''carcinoma of the lung'' * Pulmonary carcinoid tu ...
risk, with ultrafine (nanoscale) 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.


Dermal

Some studies suggest that nanomaterials could potentially enter the body through intact skin during occupational exposure. Studies have shown that particles smaller than 1 μm in diameter may penetrate into mechanically flexed skin samples, and that nanoparticles with varying physicochemical properties were able to penetrate the intact skin of pigs. Factors such as size, shape, water solubility, and surface coating directly affect a nanoparticle's potential to penetrate the skin. At this time, it is not fully known whether skin penetration of nanoparticles would result in adverse effects in animal models, although topical application of raw SWCNT to nude mice has been shown to cause dermal irritation, and ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
'' studies using primary or cultured human skin cells have shown that carbon nanotubes can enter cells and cause release of pro-inflammatory cytokines,
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
, and decreased viability. It remains unclear, however, how these findings may be extrapolated to a potential occupational risk. In addition, nanoparticles may enter the body through wounds, with particles migrating into the blood and lymph nodes.


Gastrointestinal

Ingestion can occur from unintentional hand-to-mouth transfer of materials; this has been found to happen with traditional materials, and it is scientifically reasonable to assume that it also could happen during handling of nanomaterials. Ingestion may also accompany inhalation exposure because particles that are cleared from the respiratory tract via the
mucociliary escalator Mucociliary clearance (MCC), mucociliary transport, or the mucociliary escalator, describes the self-clearing mechanism of the airways in the respiratory system. It is one of the two protective processes for the lungs in removing inhaled partic ...
may be swallowed.


Biodistribution

The extremely small size of nanomaterials also means that they much more readily gain entry into the
human body The human body is the structure of a human being. It is composed of many different types of cells that together create tissues and subsequently organ systems. They ensure homeostasis and the viability of the human body. It comprises a hea ...
than larger sized particles. How these nanoparticles behave inside the body is still a major question that needs to be resolved. The behavior of nanoparticles is a function of their size, shape and surface reactivity with the surrounding tissue. In principle, a large number of particles could overload the body's phagocytes, cells that ingest and destroy foreign matter, thereby triggering stress reactions that lead to inflammation and weaken the body's defense against other pathogens. In addition to questions about what happens if non-degradable or slowly degradable nanoparticles accumulate in bodily organs, another concern is their potential interaction or interference with biological processes inside the body. Because of their large surface area, nanoparticles will, on exposure to tissue and fluids, immediately
adsorb Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a f ...
onto their surface some of the macromolecules they encounter. This may, for instance, affect the regulatory mechanisms of enzymes and other proteins. Nanomaterials are able to cross biological membranes and access
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
, tissues and organs that larger-sized particles normally cannot. Nanomaterials can gain access to the blood stream via inhalation or ingestion. Broken skin is an ineffective particle barrier, suggesting that acne, eczema, shaving wounds or severe sunburn may accelerate skin uptake of nanomaterials. Then, once in the blood stream, nanomaterials can be transported around the body and be taken up by organs and tissues, including the brain, heart, liver, kidneys, spleen, bone marrow and nervous system. Nanomaterials can be toxic to human tissue and cell cultures (resulting in increased
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
, inflammatory
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
production and
cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as d ...
) depending on their composition and concentration.


Mechanisms of toxicity


Oxidative stress

For some types of
particles In the physical sciences, a particle (or corpuscule in older texts) is a small localized object which can be described by several physical or chemical properties, such as volume, density, or mass. They vary greatly in size or quantity, from s ...
, the smaller they are, the greater their surface area to volume ratio and the higher their chemical reactivity and biological activity. The greater chemical reactivity of nanomaterials can result in increased production of
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
(ROS), including
free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Ailments of unknown cause Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabo ...
s. ROS production has been found in a diverse range of nanomaterials including carbon
fullerene A fullerene is an allotrope of carbon whose molecule consists of carbon atoms connected by single and double bonds so as to form a closed or partially closed mesh, with fused rings of five to seven atoms. The molecule may be a hollow sphere, ...
s,
carbon nanotube A scanning tunneling microscopy image of a single-walled carbon nanotube Rotating single-walled zigzag carbon nanotube A carbon nanotube (CNT) is a tube made of carbon with diameters typically measured in nanometers. ''Single-wall carbon na ...
s and nanoparticle metal oxides. ROS and free radical production is one of the primary mechanisms of nanoparticle toxicity; it may result in oxidative stress, inflammation, and consequent damage to proteins, membranes and DNA. For example, the application of nanoparticle metal oxide with
magnetic fields A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
that modulate ROS leading to enhanced tumor growth.


Cytotoxicity

A primary marker for the damaging effects of NPs has been cell viability as determined by state and exposed surface area of the cell membrane. Cells exposed to metallic NPs have, in the case of copper oxide, had up to 60% of their cells rendered unviable. When diluted, the positively charged metal ions often experience an electrostatic attraction to the cell membrane of nearby cells, covering the membrane and preventing it from permeating the necessary fuels and wastes. With less exposed membrane for transportation and communication, the cells are often rendered inactive. NPs have been found to induce
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
in certain cells primarily due to the
mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
l damage and
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
brought on by the foreign NPs electrostatic reactions.


Genotoxicity

Metal and metal oxide NPs such as silver, zinc, copper oxide,
uraninite Uraninite, formerly pitchblende, is a radioactive, uranium-rich mineral and ore with a chemical composition that is largely UO2 but because of oxidation typically contains variable proportions of U3O8. Radioactive decay of the uranium causes ...
, and
cobalt oxide Cobalt oxide is a family of chemical compounds consisting of cobalt and oxygen atoms. Compounds in the cobalt oxide family include: * Cobalt(II) oxide (cobaltous oxide), CoO *Cobalt(III) oxide Cobalt(III) oxide is the inorganic compound with the ...
have also been found to cause DNA damage. The damage done to the DNA will often result in mutated cells and colonies as found with the HPRT gene test.


Methods and standards

Characterization of a nanomaterial's physical and chemical properties is important for ensuring the
reproducibility Reproducibility, also known as replicability and repeatability, is a major principle underpinning the scientific method. For the findings of a study to be reproducible means that results obtained by an experiment or an observational study or in ...
of toxicology studies, and is also vital for studying how the properties of nanomaterials determine their biological effects. The properties of a nanomaterial such as
size distribution Size in general is the magnitude or dimensions of a thing. More specifically, ''geometrical size'' (or ''spatial size'') can refer to linear dimensions (length, width, height, diameter, perimeter), area, or volume. Size can also be measur ...
and agglomeration state can change as a material is prepared and used in toxicology studies, making it important to measure them at different points in the experiment. With comparison to more conventional toxicology studies, in nanotoxicology, characterisation of the potential contaminants is challenging. The biological systems are themselves still not completely known at this scale. Visualisation methods such as
electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
(SEM and TEM) and
atomic force microscopy Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the opt ...
(AFM) analysis allow visualisation of the nano world. Further nanotoxicology studies will require precise characterisation of the specificities of a given nano-element: size, chemical composition, detailed shape, level of aggregation, combination with other vectors, etc. Above all, these properties would have to be determined not only on the nanocomponent before its introduction in the living environment but also in the (mostly aqueous) biological environment. There is a need for new methodologies to quickly assess the presence and reactivity of nanoparticles in commercial, environmental, and biological samples since current detection techniques require expensive and complex analytical instrumentation.


Policy and regulatory aspects

Toxicology studies of nanomaterials are a key input into determining
occupational exposure limit An occupational exposure limit is an upper limit on the acceptable concentration of a hazardous substance in workplace air for a particular material or class of materials. It is typically set by competent national authorities and enforced by legi ...
s. The Royal Society identifies the potential for nanoparticles to penetrate the skin, and recommends that the use of nanoparticles in cosmetics be conditional upon a favorable assessment by the relevant
European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body ...
safety advisory committee. The Woodrow Wilson Centre'
Project on Emerging Technologies
conclude that there is insufficient funding for human health and safety research, and as a result there is currently limited understanding of the human health and safety risks associated with nanotechnology. While the US National Nanotechnology Initiative reports that around four percent (about $40 million) is dedicated to risk related research and development, the Woodrow Wilson Centre estimate that only around $11 million is actually directed towards risk related research. They argued in 2007 that it would be necessary to increase funding to a minimum of $50 million in the following two years so as to fill the gaps in knowledge in these areas. The potential for workplace exposure was highlighted by the 2004 Royal Society report which recommended a review of existing regulations to assess and control workplace exposure to nanoparticles and nanotubes. The report expressed particular concern for the inhalation of large quantities of nanoparticles by workers involved in the manufacturing process. Stakeholders concerned by the lack of a regulatory framework to assess and control risks associated with the release of nanoparticles and nanotubes have drawn parallels with
bovine spongiform encephalopathy Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is an incurable and invariably fatal neurodegenerative disease of cattle. Symptoms include abnormal behavior, trouble walking, and weight loss. Later in the course of t ...
(‘mad cow's disease'),
thalidomide Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications o ...
,
genetically modified food Genetically modified foods (GM foods), also known as genetically engineered foods (GE foods), or bioengineered foods are foods produced from organisms that have had changes introduced into their DNA using the methods of genetic engineering. Gene ...
, nuclear energy, reproductive technologies, biotechnology, and
asbestosis Asbestosis is long-term inflammation and scarring of the lungs due to asbestos fibers. Symptoms may include shortness of breath, cough, wheezing, and chest tightness. Complications may include lung cancer, mesothelioma, and pulmonary heart ...
. In light of such concerns, the Canadian-based ETC Group have called for a moratorium on nano-related research until comprehensive regulatory frameworks are developed that will ensure workplace safety.


See also

*
International Center for Technology Assessment The International Center for Technology Assessment (ICTA) is a U.S. non-profit bi-partisan organization, based in Washington, D.C. ICTA was formed in 1994. Its executive director is Andrew Kimbrell. Its sister organization is the Center for Food S ...
*
Toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating e ...


References


External links

* {{cite web, url=http://www.nanowerk.com/spotlight/spotid=1382.php, last=Berger, first=Michael, publisher=Nanowerk LLC, title=Toxicology - from coal mines to nanotechnology, date=2007-02-02, access-date=2007-05-15
The Center for Biological and Environmental Nanotechnology (CBEN), Rice University
Toxicology Nanomedicine