1. INTRODUCTION:

Nanoparticles from metal and metal oxide are able to provide great benefit to mankind. Smaller get unique chemical and physical properties due high surface to volume ratio and they are more toxic than their bulk materials. The researchers show interest in development, characterization and application of nano particles. The toxic effect of these particles also should be considered for the safety use of them. Nano particles of some metal oxides can generate reactive oxygen species which cause oxidant injury [1]. The mechanism of toxicity should be known for finding the remedial measures, which is the information about absorption, distribution, metabolism and excretion of nanoparticles and validated detection methods of these man-made nanoparticles. The proper knowledge of detection, dose, and mechanism of reaction should be identified [2]. Nano particles enters the body through different medium (eg: air, soil, water) their properties are different bulk material.

Nanoparticles of individual metals and metal oxides enters the respiratory tract, metal powders especially metal vapours damage mucous membranes and cause respiratory viral infections, chronic pharyngitis and bronchitis to individuals[3]. Nanoparticles which are inhaled deposited in the nasopharynx or get down to the alveoli. These nanoparticles get to other part of the body via transcytosis through cell layers, and/or through the blood stream, sensory nerves endings provide a direct pathway for nanoparticles to the brain. Smaller size, high number of concentration, and large specific surface area make the nano particles to greater biological activity per given mass than larger particles [4]. Helping information should be provided to develop nanomaterials in safety standards and safety use of them. Nanoparticles may cause potential functional and toxicity effects on human neural cells owing to their ability to pass through biological membranes. Human neural cells such as hippocampal cells in the central nervous system are the most sensitive and delicate cells of bio organisms- any adverse effect on this system by nano particles may produce serious problems in nervous systems. This is important to ensure that their applications are safe and provide helpful information to develop nanomaterial safety standards [5].

2. NANOPARTICLES OF METALS:

2.1. Lead:

Lead is toxic even at low doses and a ubiquitous pollutant. Smelting of lead and metal fumes emit lead particles to the environment. It may affect the nervous system, and makes brain damages, creates learning disabilities and behavioural problems and learning impairment in children. Various central and peripheral evoked activities are reported due to inhaling of lead [6]. Lead accumulates in central nervous system, first of all in the cortex and hippocampus, and produces encephalopathy at blood levels [7]. Disruption of biosynthesis of haemoglobin and hence anaemia, rise in blood pressure, kidney damage, miscarriages and subtle abortions, declined fertility of men through sperm damage, decreased hearing, and impaired cognitive functions in humans etc are also reported as the toxic effect of lead [8].

2.2. Cadmium:

Cadmium particles gets to the environment from industrial wastes (batteries, pigments, alloys, metal dusts, fumes etc) and tobacco smoke. This is considered as one of the most toxic environmental pollutants and human carcinogen which damage the lungs, liver, kidney, testis, brain etc [9]. Long term inhalation causes neurotoxic consequences like amyotrophic lateral sclerosis, optic nerve damage, striatal damage and peripheral polyneurophathy [10]. Cadmium poisoning in respiratory truck develops Parkinson like state that is difficult to cure with antiparkinsonian medication. Striatal damage, peripheral polyneuropathy, optic nerve damage and amyotrophic lateral sclerosis are the observed long term neurotoxic consequences of cadmium. The behavioral problems are reported in children due to inhaling of cadmium [11].

2.3. Manganese:

Exposure of welding and industrial works creates manganese particle as considered as neurotoxicant [12]. Inhalation manganese cause metal fume fever or manganese pnemonitis [13]. Apathy, anorexia, asthenia, headache, hypersomnia, spasms, arthralgia, weakness of the legs and irritability are the after effect of continues inhalation manganese particles. Effect of manganese inhalation comes through three different stages. Metal fume fever or manganese pneumonitis are the first stages. Psychomoto and psychic disturbances such as dysarthria, excess salivation and difficulty in walking are second stage of neurological disorders. Parkinson like syndrome is the last stage of manganese continues inhalation [14].

2.4. Silver:

Dusts of fumes containing silver, burn creams, dental amalgams, etc are sources which can enter the silver particles in human body [15]. Inhaled silver deposited in the lung can be absorbed through the wall of the alveolus, silver particles do not interfere with microcilliary elimination process, at the alveolar region these particles can be submersed into the surfactant lining of alveoli. Due to this submersion, naoparticles can produce surface radicals and reactive oxygen species which are more toxic to alveolar surfaces [16]. Silver also accumulates in liver, kidney and spleen. Continues exposure of silver leads to irreversible deposition in subcutaneous and mucous membranes [17]. Melanin production is enhanced due to this deposition leading to discoloration of the skin. Phytohaemagglutinin induced cytokine production was also significantly inhibited by nano-silver. Nanoparticles of silver are 50% percentage more toxic than chrysolite asbestos. Nanoparticles of silver affect the male reproductive system. Nano particles cross the blood-testes barrier and are deposited in the testes, and that there is potential for adverse effects on sperm cells. Nanoparticles can directly enter to brain by tans-synaptic transport. Impairments to normal neurons, microglia and aggravate the process of brain pathology occurs due to impairments to normal neurons. Exposure, contact time, strength of binding and weight loading should be considered to predict the effect of metallic particles in animal body [16].

2.5. Iron:

Henderson et. al reported iron inhibits serum lactate dehydrogenase serum in mice. Nano iron particles might have some different effects compared to micro size iron particles and ferric oxide materials to lactate dehydrogenase isoenzyme. Iron nanoparticles have several biomedical applications, but they can interfere with formation of nerve cells` signal transmitting extensions [18].

2.6. Zinc:

Lethargy, vomiting and diarrhea are occurred in mice due to inhalation of nano scale zinc. Death of mice occurred due to continuing inhalation about 2weeks. The acute toxicity of oral exposure to nanoscale zinc powder is evaluated. 5g/kg of nano scale and micro scale zinc particles are gastro intestinally administered. The blood coagulation was studied after 2 weeks [19]. The nano scale zinc treated mice had shown more severe symptoms of lethargy, vomiting and diarrhea in the beginning days than the micro scale zinc mice. Deaths of two mice occurred in the nanoscale zinc conception after first week of treatment [20].

3. NANO PARTICLES OF METAL OXIDE:

3.1. Zinc oxide:

Zinc oxide has strong absorption abilities for series of organic compounds and heavy metals. Cosmetics and modern sunscreens have zinc oxide as ingredient. Zinc oxide is an important ingredient in cosmetics and modern sunscreens, nano particles are considered as safe for human than micro particles, but their toxic effect should be considered. There was no sign of penetration of zinc oxide nanoparticles, when sunscreen formulation of nano zinc oxide contacted with skin [21]. Zinc oxide is important in industry due to its strong absorption abilities for series of organic compounds and heavy metals. Zinc oxide is an important ingredient in cosmetics and modern sunscreens, there is no sign penetration zinc oxide nanoparticles, when zinc oxide contacted with skin [22].

Chuan-Chin Huang et al. reported the toxicity of zinc oxide nanoparticles are time dependent and concentration dependent. When ZnO nanoparticles are exposed to mice via the digestive tract, primary organs were damaged but spleen and brain cells were normal at low concentration. Zinc oxide also increases the intracellular calcium levels [23]. The toxic difference of different ZnO particles mainly depended on the effect of nondissolved ZnO particles. ZnO nanoparticle toxicity comes from the dissolved Zn²⁺ in the culture medium or inside cells [24].

3.2. Copper (II)oxide:

Frequent inhalation and high doses CuO cause severe acute inflammatory changes and had shown lung carcinogenic bioassays [25]. Cytotoxicity and DNA damage in the human lung epithelial cell line reported due to inhalation of CuO nanoparticles [26]. CuO Nanoparticles generate reactive oxygen species and they also block cellular defenses. Chlorophyll content of duckweed decreased by consuming copper oxide nanoparticles, and that CuO nanoparticles toxicity is three to four times higher than that of ionic Cu, because of larger uptake of nanoparticles release Cu [27].

CuO toxicity increased with increasing concentration of greater than micron particles. CuO nanoparticles have been shown toxic effects in bacteria, yeast, microalgae, crustaceans, and zebrafish [28]. Copper oxide causes significant cell death among epithelial cell lines, while iron oxide, titanium dioxide and silica nanoparticles appeared to have little or no cytotoxic effect. Cytotoxicity copper oxide nanoparticles is due to autophagy or cellular self digestion, which is a conserved mechanism involved in the degradation of proteins and organelles in the cytoplasm. Autophagy primarily serves as a pro survival mechanism in contexts including nutrient and growth factor deprivation [29, 30]. The significant reduction in glutathione and induction in lipid peroxidation, catalase, and superoxide dismutase in HaCaT cells and decrease in cell viability were observed with CuO nanoparticles. Apoptsis or necrosis was observed due to CuO nanoparticles, DNA damage mediated by oxidative stress induced by CuO nanoparticles. Exposure of 0.1 to 0.4 g/L nanoparticles in water during 48hours induced strong inhibition of photosynthetic processes resulting in a decrease of plant growth [31].

3.3. Titanium oxide:

Titanium oxide generates more reactive oxygen species in light, the overproduction of reactive oxygen species led to the breakdown of balance of the oxidative/antioxidative system, resulting in the lipid peroxidation and death of cells. TiO₂ nano particles under light conditions are more toxic than in the dark. Nano sized particles of titanium oxides are more toxic than micro-sized particles [32].

Lab experiments in mice had shown TiO₂ nanoparticles cause similar effects to asbestos and silicone, activating the inflammasom NLRP3- a complex mechanism responsible for activating inflammation processes – and releasing molecules capable of attacking DNA, proteins and cell membranes. Titanium dioxide accumulates like asbestos in lung and may change reason for cancer [33]. In vivo or in vitro studies are not reported nanoparticles do not penetrate the stratum corneum. But intravenous exposure of titanium oxide nanoparticles induces pathological lesions of the liver, spleen, kidneys and brain. The most of these effects are due to use of very high doses of TiO₂ nanoparticles. The published results on nanoparticles cytotoxicity and genotoxicity such as titanium dioxide nanoparticles (TiO₂ NPs) are inconsistent, and often conflicting and insufficient [34].

3.4. Cerium oxide:

The cytotoxicity and oxidative stress caused by 20-nm cerium oxide (CeO₂) nanoparticles in cultured human lung cancer was investigated [35]. The toxic effects of cerium oxide nanoparticles are dose dependent and time dependent. The property cerium oxide to inhibit the cell activity reduces the number of blood cells at high concentration. Cerium oxide stimulate oxidative stress in cells and reduces cellular antioxidants, it increases the involvement of cells in the immune processes. The distribution and effect of nanoparticles in tissues depend on diameter changes [36].

Cerium oxide nanopartilces can enter into lymphatic system, inflammation occurs in lymph nodes, this condition occurs at high concentration of nanoparticles. Cerium oxide nanoparticles can enter into lymphatic system; then inflammation occurs in lymph nodes. The induced inflammation in the lymph nodes helps to increasing the number of white cells, but after a special period, the activity of these glands become weakened and atrophy of lymph nodes make them irreversible. 200ppm concentrations of cerium oxide nanoparticles reduce the number of white blood cell [37, 38].

4. CONCLUSION:

Nanoparticles have impact on human body, when it is get inside the body through any of the way. The available studies have shown several effects in animals, depending on the type of nanoparticles. The unique size and size dependent properties make these material superior than other particles, due to the same reason it may creates dangerous effect. The way nanoparticles get inside and the effect of these particles after inhalation should be learned and find the proper remedial measures before the large scale usage. The toxicological data is partial; review is limited with current informations. The available studies have shown several effects in animals, depending on the type of nanoparticles. Metals and metal oxides are most commonly synthesizing materials due to the easiness of way of synthesizing and eccentric applications. This paper discus about the common toxic effects of these particles, knowing about the effect helps to find remedial measures, or finding an alternative for more harmful materials, or control and individual protection in implementation and use of nanoparticles. Source elimination, exposure control and individual protection, in production, and in implementation and use of these products have to be maintained with proper planning.

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Received on 12.09.2013 Modified on 21.09.2013

Asian J. Research Chem. 6(12): December 2013; Page 1179-1182