Veterinary World 2011, Vol.4 (1):35-40 REVIEW Nanotoxicology: An Emerging Discipline

Nanotoxicology refers to the study of the interactions of nanostructures with biological systems with an emphasis on elucidating the relationship between the physical and chemical properties of nanostructures with induction of toxic biological responses. Nanotoxicology is aimed at providing information on the potential toxicological effects, risk assessment and safety evaluation of nanostructured materials on human health. Nanoparticles present possible dangers, both medically and environmentally. They are also able to pass through cell membranes in organisms and their interactions with biological systems are relatively unknown. Animal studies have shown that nanoparticles can penetrate cells and tissues, move through the body and brain and cause biochemical damage. The greater chemical reactivity of nanomaterials result in increased production of reactive oxygen species which may contribute to similar patterns of cell injury and alterations at the molecular level by initiation, propagation and autocatalytic chain reactions. Intracellular signaling activation and inactivation of enzymes, stimulation, secretion and release of pro-inflammatory cytokines, chemokines and nuclear factor activation and alteration are also common events.


Introduction
size, shape, surface chemistry, composition, and aggregation) of nanostructures with induction of toxic A wide variety of nano-structured materials are biological responses.now used in commodities, pharmaceutics, cosmetics, Nanotoxicology is aimed at providing biomedical products, and industries.While nanoscale information on the potential toxicological effects, risk materials possess more novel and unique physicoassessment, and safety evaluation of nano-structured chemical properties than bulk materials, they also materials on human health for a wide audience, have an unpredictable impact on human health.The including those working in the fields of nanoscience entrance into and interaction of nanomaterials in the and nanotechnology, biology, toxicology, chemistry, human body have generated intense scientific chemical biology, medical sciences, public health curiosity, attracting much attention as well as sciences, standardization of nanotechnology increasing concern from the public, nanomaterial-(nanosafety standards) as well as for policy makers based industries, academia, and governments developing regulatory frameworks in government worldwide.(Dreher, 2004) departments and nanotechnology industries /enterprises.The development of technology enables the Nanotoxicology, dealing with the potential impact of reduction of material size in science.The use of nanoparticles on human and animal health and particle reduction in size from micro to nanoscale not environment, evolved as a new field of research only provides benefits to diverse scientific fields but (Yezhelyez et al., 2006).also poses potential risks to humans and the The smaller a particle, the greater it's surface cancer Welding fume Welding processes Inflammation; area to volume ratio and the higher its chemical translocation of metals to the brain Fly-ash Combustion reactivity and biological activity.The greater chemical of coal or oil inflammation Nanoparticle Carbon black reactivity of nanomaterials results in increased Combustion of heavy fuel oil Inflammation, lung cancer; production of reactive oxygen species (ROS).translocation of particles to the brain (Salata, 2004) ROS production has been found in a diverse (ii) Manufactured derived nanoparticles: range of nanomaterials including carbon nanotubes Manufactured nanoparticles display physicoand nanoparticle metal oxides.ROS and free radical chemical characteristics including electrical, thermal, production is one of the primary mechanisms which mechanical, and imaging properties that are highly may result in oxidative stress, inflammation and desirable for applications in commercial, medical and consequent damage to proteins, membranes and DNA.environmental sectors (Masciangioli and Zhang, 2003).
Both in vivo and in vitro, Nanosized particles of (iii) Naturally occuring nanoparticles: various chemistries have been shown to create reactive Biologically based or naturally occuring molecules oxygen species (ROS).ROS production has been that are found inside organism.For example; biogenic magnetite is a naturally occuring nanosized particle that found in Nps as diverse as C60 fullerenes, SWNTs, occurs in many species ranging from bacteria to quantum dots, and UFPs, especially under protozoa, to animals.Biogenic magnetite is even been concomitant exposure to light, UV, or transition metals found in brain and has been associated with neuro (Brown et al., 2000(Brown et al., , 2001;;Derfus et al., 2004; Joo et degenerative diseases (Antunes et. al, 2007).

Nanomaterials in the environment
compositions preferentially mobilize to mitochondria During the manufacture, transport, use and (Foley et al, 2002;Rodoslav et al., 2003).Because disposal of nanomaterials and those products containing mitochondria are redox active organelles, there is a nanomaterials, the release of these materials into the likelihood of altering ROS production and thereby environment is inevitable.As the use of nanomaterials overloading or interfering with antioxidant defenses.increases, so too will their presence in the environment.

Some of the antioxidant defense systems that
The details are given in the Table - available portal of entry even for larger particles.

Translocation of Nanoparticles
Subsequent translocation of nano size particle beyond  2006).They are also able to pass through cell mechanism involves passing of nanoparticles across membranes in organisms, and their interactions with epithelia of the respiratory tract into the interstitium biological systems are relatively unknown.and access to the blood stream directly or via According to the San Francisco Chronicle, lymphatic pathways, resulting in systemic distribution "Animal studies have shown that some nanoparticles of nanoparticles.Berry et al (1977) observed the can penetrate cells and tissues, move through the body presence of nanoparticles in rat platelets after and brain and cause biochemical damage.Diesel intratracheal instillation of colloidal gold particles (30 nanoparticles have been found to damage the nm).Once nanoparticles are translocated into the cardiovascular system in a mouse model (Royal blood stream they could induce adverse biological Society and Royal Academy of Engineering, 2004).effects (Oberdorster et al., 2004).
Lungs : One of the most important portals of entry and

Central nervous system
organ target for nanoparticles is the respiratory The translocation of nanoparticles to central system.It is well known that lungs are easily exposed nervous system takes place as a result of systemic to atmospheric pollutants and many other products of distribution.The other mechanism involves the uptake thermo-degradation.In this regard, combustionof nanoparticles by sensory nerve endings embedded derived nanoparticles have been largely studied as a in airway epithelia, followed by axonal translocation possible etiologic factor for several adverse health to ganglionic and CNS structures.In addition, effects, including exacerbations of airways disease as nanoparticles can be taken up by the nerve endings of well as deaths and hospitalization from cardiovascular the olfactory bulb and translocated to the CNS disease (Donaldson, 2005).(Letham, 2003).
Researchers in the University of Texas in the

Gastrointestinal tract
Nanosize particle cleared from the respiratory United States found that carbon nanotubes squirted tract via the mucociliary escalator can subsequently be into the trachea of mice caused serious inflammation ingested into the gastrointestinal tract.Alternatively, of the lungs and granulomas (tumour-like nodules of bloated white blood cells in the lining of the lungs), (CD) is an inflammatory chronic condition whose and five of the nine mice treated with the higher dose aetiology remains still unclear (Chen et al., 2006).It died (Oberdorster et al., 2005).In yet another similar has been shown that a diet low in Ca++ and exogenous experiment in Tottori University, Japan, researchers microparticles alleviated the symptoms of human CD showed that within a minute of contacting the mice's with a significant improvement in the CD activity tiniest airways, carbon nanotubes began to burrow index (Jani et al., 1994).These results are particularly through gaps between the surface lining cells and into relevant to CD as an abnormal intestinal permeability the blood capillaries, where the negatively charged has been found in this disease (Szentkuti, 1997).nanoparticles latched onto the normally positively Liver: The effect of Quantum dots on liver cells was charged red blood cells surface, thereby potentially examined by Roco (2003) in the University of causing the red blood cells to clump and the blood to California.Researchers found that cadmium-selenium clot (Lam et. al., 2004).
quantum dots were acutely toxic to rat liver cell Heart : The Institute of Occupational Medicine U.S. cultures at doses similar to that expected for human shows that various nanoparticles when introduced into exposure.the bloodstream can cause heart tissue damage.This The reticulo-endothelial system located in the arises through oxidative stress and inflammation liver is exposed to all nanoparticles absorbed from the leading to apoptosis and necrosis (Yoshifumi, 2002).
gastrointestinal tract (GIT) into the cardiovascular Some reports show that nanoparticles system, since all blood exiting the GIT does so in the particularly Calcium nanoparticles produce heart hepatic portal vein that directly diffuses through the attacks.In an experiment, scientist injected lab liver.Low toxicity Nanoparticles such as carbon black animals' artery walls with these Calcium and polystyrene stimulate the macrophages via nanoparticles and the walls became inflamed.reactive oxygen species and calcium signalling, to Inflammatory response is a first step towards make pro inflammatory cytokines such as tumour hardening (Oberdorster et al., 1995) necrosis factor alpha (Chad and Andrew, 2000).Brain: In some of the experiments conducted by using Oxidative stress is known to inhibit hepatocyte mice brain cell cultures found that introducing function and bile formation, while pro-inflammatory nanoscale titanium dioxide caused oxidative stress in cytokines are also associated with the pathology of neurons.This is of concern as the oxidative stress of liver disease (Yoon et al., 2005).neuron cells has been linked with neurodegenerative Skin: Nanomaterials such as nanoscale titanium diseases.
dioxide and zinc oxide have widespread use in A number of pathologies, including hyper-ointments and creams; therefore, an understanding of tension and allergic encephalomyelitis, however, have their effect on skin is essential in assessing the risk to been associated with increased permeability of the both human and animals.The widespread environblood brain barrier to Nanoparticles in experimental mental presence of other manufactured nanomaterials set ups.The nanoparticle surface charge has been could also lead to skin exposure.shown to alter blood-brain integrity and need Initial studies showed that certain nanomaterials consideration as to their role in brain toxicity and brain can cause damage to skin cells as well as pass through distribution.
the epidermal (outermost) layer of skin into deeper Nanoparticles have been shown to induce the layers and subsequently into the body and production of reactive oxygen species and oxidative bloodstream.stress has been implicated in the pathogenesis of Due to their small size, nanomaterials also have neurodegenerative diseases such as Parkinson's and the potential to be absorbed through the skin and enter Alzheimer's (Dagani, 2003).
the blood stream or lymphatic system (M.I.T., 2007).Gastrointestinal tract: Another portal of Nanoparticles can also be taken up by lymphatic nodes nanoparticles entry in the body is GI tract.at skin level, translocating to the blood stream via Nanoparticles can be ingested into the gut by many lymphatic pathways (Kim et al., 2004).ways, such as; nanoparticles can be ingested directly Plants: Nanoparticles could have a negative effect on from the food, water and drugs (Hoet et al., 2004).
plant growth and have the ability to cause injury to Recently, it has been shown that Cu nano-plants.A new study examined the effects of five types particles administered via oral gavage can induce an of nanoparticles on seed germination and root growth inflammatory response leading to bowel disease that of six higher plant species and observed that several includes both ulcerative colitis and Crohn's disease types of the particles had significant inhibition on seed the successful application of (I) Combustion-derived nanoparticles (CDNP): nanomaterials in bioscience, it is essential to Combustion-derived nanoparticles present a understand the biological fate and potential toxicity of diverse group of materials which gain commonality nanoparticles.(Colvin, 2003).because of their origin in combustion processes and Nanotoxicology refers to the study of the their demonstrated toxicity in various models.interactions of nanostructures with biological systems Common examples are diesel exhaust particles, with an emphasis on elucidating the relationship welding fumes, fly-ash.between the physical and chemical properties (e.g.CDNP Origin Reported Health effects Diesel exhaust surrounding tissue.particles Combustion of diesel oil Inflammation, fibrosis,

may Mechanism of action of nanoparticles create
3. oxyradicals.The exact mechanism by which each of these diverse NPs cause ROS is not yet fullyThe behavior of nanoparticles is a function of understood, but suggested mechanisms include: their size, shape and surface reactivity with the occur in animals, and possible areas where NSPs

Toxicity of Nanoparticles defences
in the respiratory system and gain access to Nanoparticles present possible dangers, both the systemic circulation or even to the central nervous medically and environmentally.Most of these are due system.Once inhaled and deposited, nanoparticles can to the high surface to volume ratio, which can make the translocate to extra pulmonary sites and reach other particles very reactive or catalytic.(Wiesner et al., target organs by different mechanisms.The first