Abstract
In recent years, nanotechnology has reached the limelight of research in applications of medicine and technology. Due to its onset, huge varieties of nanoparticles possessing significant characters are synthesized with broad application fields. Even though these particles are infesting our present life; conflictual views regarding their medical and biological effects are debatable. The non biodegradable nature and nanosize are the alarming features of the nanoparticles that confront potential threats to both environment and biomedical field on its expanding usage. NPs synthesized from heavy metals like lead, mercury and tin are proclaimed as stringent and stable compounds for degradation, hence results in environmental biohazards. The extensive applications of silver nanoparticles in biosensing, cosmetics, medical devices, food and clothing products inflates its human exposure and obviously resulted in toxicity (short and long term). In vitro studies revealed various cytotoxic effects in the cells of mammals such as brain, liver, lung, skin, reproductive organs and vascular system. Furthermore, ingestion, inhalation or injection of nanoparticles in intraperitoneal region resulted in toxic effect of multiple organs inclusively brain. Accounting the metal nanoparticles biohazardous effects like ROS (Reactive oxygen species) generation, DNA damage, protein denaturation and lipid peroxidation has been proved on carbon based nanoparticles, organic lipid based nanoparticles, mineral based nanoparticles, nano diamonds, nano composites, etc. Although, nanotechnology has become an advent field of research nowadays, it is importing significant environmental and health hazards thus couldn’t be beneficial to both society and economy.
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1 Introduction
Existence of nanoparticles (NPs) is uncertain, over million years ago and their employment by humans is about thousands of years. Because of the accelerated human capacity in nanoparticle synthesis, enough attention has been directed on this type of particles. Due to their compelling potential of usage in wide areas like electrical industry, pharmaceuticals, cosmetics, medical and environmental applications, their respective investments are also growing worldwide (Guzman et al. 2006). The imperative fact about nanotechnology is the consideration of scientists as the lucid step of science to integrate biology, chemistry, physics, medicine and engineering (Chen and Mao 2007; Dahl et al. 2007; Vo-Dinh 2007; Janata 2008; Stewart et al. 2008).
The applications of nanotechnology has inclined greatly from the laboratory to economic market with huge interest scientifically through pharma industry. The particles right from the distinct nano to sub-micron sized were engaged widely in food, pharmaceuticals and cosmetics industries. In pharmaceutical industries nanoparticles were employed adversely as carriers of drug delivery, imaging, diagnostic agents of oncology and in diabetes. In the flourishing field of pharmaceuticals the nanotechnology are engaged with great potential through oral, dermal and injectable routes. As per FDA, 25 nanoparticles has been approved to use in enormous drug delivery systems, which implies its competency in treating diseases (infectious and non infectious). Nanomaterials are worn in numerous forms like nanotubes, nanomembranes, nanoparticles, nanofibers, liposomes, nanofilms etc. In pharmaceutical industries, lipid based nanoparticles (nanolipidsomes, lipid nanoparticles, nanoemulsions, lipid nanocapsules, lipid polymer nanoparticles), dendrimers, nanoshells and fullerenes were extensively studied in drug delivery systems of both academics and industries. Apart from these, some emerging particles includes, metal nanoparticles, nanodiamonds, carbon nanotubes, graphene nanoparticles and quantum dots, they were used in diagnosis, drug delivery and imaging so as to achieve decisive targeting upon organs and cells.
The probable toxicity of metals that are accounted herein was well rooted since roman times and not new. Pedanius Dioscorides, the greek physician has previously described the probable effects of metals like mercury (Caley 1928), lead oxide (Osbaldeston and Wood 2000), copper silicate (Wisniak 2004), poisonous effects of Arsenic in yellow and red sulfur mines as referred by Strabo (Cilliers and Retief 2000) and demise of Alexander, the great as a consequence of drinking contaminated water of River Styx (Atkinson and Truter 2009). In the initial part of the present century, toxicity of metals and toxic effects of the excessive tiny particles were explored (Donaldson et al. 2001).
Expulsion of nanoparticles from consumer’s body is pivotal. It is vital to determine the exceeding nanoparticles to overcome adverse effects (Kantiani et al. 2010). It was determined from the ancient times that dose of poison was ample to evoke a response. Nonetheless, size, physicochemical properties and mode of entry of nanoparticle will influences to determine persistence, hazard threat and biotoxicity so as to formulate and implement safety patterns (Scott-Fordsmand et al. 2014). The unwelcome consequences of the nanoparticle exposure are health ailments due to cytotoxicity, genotoxicity, cancer and autoimmune diseases.
The primary concern regarding the employment of metals within living organisms is their corroding and degrading ability results in diminished toughness, disintegration and weakening of accounted implants. Their activity would be diminished by the curtailing effects of biocompatibility and escalation of toxic effects (Burugapalli et al. 2016; Khodaei et al. 2016). The components like dissolved oxygen, soluble carbonates, nitrogen and electrolytes along with some physiological fluids (proteins, enzymes, organic acids and macromolecules), secretory compounds of inflammatory and fibrotic cells are responsible for progress of metal degradation which are made possible by the inhabitance of stress, strain and frictional forces.
Concerning on the biosafety of health and environmental issues into account the risk factors of NPs should be assessed prior to its application. Additionally, engineered nanoparticles could be released into the water bodies during the manufacturing and utilization processes unaviodably. Some environmental factors includes UV radiation, dissolved organic matter, ionic strength and pH could possibly react with the NPs, then the converted NPs make toxic effects on the concerning environment (El Badawy et al. 2010; Levard et al. 2012).
The undenied biocompatibility nature of NPs were contemporarily swamped off by the biotoxicity effects. Understanding of their properties relating to biological responses is vital so as to understand the flawless usage of nanoparticles. The mechanism of the nanoparticle reckons on respective factors like composition, chemical functions, shape along with its exclusive size and charge (Goodman et al. 2004; Roiter et al. 2009; Simon-Deckers et al. 2009; Xiao et al. 2012; Silva et al. 2014). Moreover, probable risk of nanoparticle resides on its respective particle size below 100 nm (nanoparticle). Based on the nanoparticle nature (metal or magnetic), the breakdown mechanism that arise within the body results in unpredictable and noteworthy toxic effects. Since, NPs are involving in numerous catalytic and oxidative mechanisms in vivo, it is very hard to predict. Nanomaterials that exposing reactive surfaces with very high surface area are attractive for specific objectives. Beddoes et al. (2015) has conferred from both in vitro and in vivo examination of human cells along with membranes and succeedingly addressed that (a) Efficient translocation of nanoparticle through the membrane that resulting in cellular damage has been made possible by small NPs, whilst nanoparticles of large size displays active cellular uptake without toxic effects, (b) Disruption of membrane integrity was made by nanoparticles of positive charge rather than negative charged particles.
The nanomaterial field is very extensive with diverge toxicity, in the present review, few nanoparticle effects were highlighted as examples to predict the disturbances in biological systems. The study of nanoparticle toxicity towards any biological substances (animals and plants) are known as nanotoxicology, which comprises in vitro studies using cell lines of human or animal, in vivo experiments using human volunteers and animals, along with epidemiological data regarding the pollution of particle and studies of workers those who are exposed to nanoparticles (during welding, mining, etc.). Applications of nanoparticles are being inflated nowadays in agriculture field in the form of agrochemicals.
Toxicity induced by nanoparticle involves in evolution of oxidative stress (free radical or liberation of reactive oxygen species (ROS), genetic damage, inflammation and suppression of cell division which results in apoptosis. In addition, ROS stress accounts for fibrosis, inflammation, genotoxicity followed by carcinogenesis through the liberation of adverse cytokines. Above all the vital mechanism of toxicity resides on the reactive oxygen species generation, such that free radical possess detrimental impacts over biomolecules (DNA, lipids, proteins). Numerous biological mechanisms like endocytosis, phagocytosis with its processing (antigen presentation on MHC class molecules) and passive diffusion reckon on the particle size of nanoparticles (gold, silver, nickel, titanium, carbon nanotubes). The large surface area of NPs contributes to few toxic indications of biological molecules that confers oxidation results in DNA damage than the larger particles with similar size (Gatoo et al. 2014). The factor that contributes the difference between nanoparticle and large particle composed of same material are the quantum effects and its respective surface (Buzea and Pacheco 2017). The nanosized material displayed diverge properties (physical, chemical and mechanical) rather than the bulk sized particles. As a consequence of the proportion of atoms found exposed on the surface of the nanoparticle correlated with the interior surface escalates results in boost up of its physical (increased surface area along with volume ratio, and shortened melting point) and chemical properties (higher chemical reactivity). By the cause of the small size of the nanoparticles (gold, palladium and platinum), the electrons confined and possess quantized spectrum of energy, producing quantum size effects like magnetic moments.
The nanomaterials are prone to contaminate the vulnerable water ecosystem directly or indirectly so as their possible toxicity to aquatic biota should be evaluated. Adverse effects like inhibition of algal growth, behavioural changes associated with severe mortality rate in water fleas (Daphnia species), damage in fish brain cells and changes in molecular biomarkers were explored. But, interaction of aquatic biota with nanomaterials, and their respective destiny in water is least recognized still. Along with the coastal progression, NiO nanoparticles separated during welding has turned into the vital sources of coastal pollution (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans). These NiO nanoparticles can be enforced as risk factors for the environment and health of human. The risk associated with inhalation of NiO nanoparticles by mammals were well established in in vitro assays (Oyabu et al. 2007).
Even though the nanoparticles acquire huge beneficial applications in the fields of agriculture, environment, medical diagnosis and treatment, some hazardous effects were also observed in animal models, human, plants, and water bodies of the environment. The fundamental complication explored by the nanoparticles are their ability to enter into the cells and concludes in cytotoxicity to inhibit their growth and development respectively. This chapter probes the biohazardous effects of different nanoparticles towards various hosts and habitat. Analysing those detrimental effects of nanoparticle would grant a wide view upon commercialization of nanoparticles in the field of agriculture, medicine and environment.
2 Factors Responsible for the Toxicity of Nanoparticles
The shape, size, surface charge, crystallinity, aggregation and surface coating of NPs are some of the factors responsible for the toxicity of nanoparticles.
The shape dependent toxicity is associated to the metal nanoparticles (gold, silver, nickel, titanium) and engineered particles (Carbon nanotubes). The nanoparticle entry into the cell by endocytosis and phagocytosis have serious impact due to the shape of the nanoparticles. For example spherical shaped nanoparticles are very prone to endocytosis when compared to other shapes of nanoparticles (Gatoo et al. 2014). Investigations revealed that the shape of the particle could affect the cellular level. K+ ion channel blockage is three times higher by rod shaped Single walled nanotubes (SWNTs) than the spherical shaped C60 fullerene (Park et al. 2003). ZnO nanorods are confirmed to be more cytotoxic than the spherical ones (Hsiao and Huang 2011).
The size of nanoparticle is also inevitable in cytotoxic effects. Asbestos fibres of <2 µm size could cause asbestosis, whereas asbestos with <5 µm size cause mesothelioma and 10 µm sized asbestos would results in carcinoma (Lippmann 1990). Similarly 15 mm length TiO2 fibres are more toxic than the 5 mm length fibres, which cause inflammatory response by alveolar macrophages in mice. Long multi walled carbon nanotubes (MWCNTs) can cause inflammatory response in abdominal cavity of mice than the small MWCNTs (Poland et al. 2008).
The surface charge of the nanoparticle employs vital impact over toxicity. The charge of the nanoparticle directs huge interactions like selective absorption, blood brain barrier integrity, plasma protein binding and membrane permeability. For example, negative charge carrying mammalian cell membranes improves interaction with cationic particles with the cells to a terrific degree than the negative or neutral nanoparticles. Nonetheless greater cationic charge results in serious toxicity through hemolysis and aggregation of platelets (Gatoo et al. 2014). Silica NPs which carry positive charge are shown to induce ROS than the silica NPs with negative or neutral charge (Bhattacharjee et al. 2010).
Several studies have reported that TiO2 (anatase form) could results in toxicity thereby inducing DNA damage with higher lipid peroxidation in the presence of light whereas the rutile form couldn’t results in any toxic effects (Gurr et al. 2005).
Aggregation of particles could also conveys toxicity. Aggregation of the particles mostly imparts on the size, surface charge and particle composition. For example, aggregated carbon nanotubes (CNTs) will have more cytotoxic effect than the dispersed ones (Wick et al. 2007).
The physiochemical properties of NPs like surface charge, chemical, magnetic, optical and electric charge can altered by the surface coating of the particles. These changes can eventually results in interactions with biomolecules to produce significant nanoparticle toxicity. For example, the presence of oxygen radicals with heavy metals and ozone on surface of nanoparticles results in ROS formation and triggers cell inflammation. In certain cases the surface coating is essential to subside the NP toxicity. For example, essential coating in quantum dots made them non toxic because of their hydrophobic metal core and toxic heavy metals like cadmium (Talkar et al. 2018).
3 Nanoparticles in Agriculture Field
3.1 Phytotoxicity of Nanoparticles
The efficient uptake of nanoparticle is very specific depending on the plants. The factors involved in uptake are type and physicochemical properties of the nanoparticle, species and substrate of the plants (Arruda et al. 2015; Zuverza-Mena et al. 2017). Translocation of nanoparticle within the plants are made by establishing complexes between root exudates and transporter proteins (Yadav et al. 2014). Roots could intake tiny nanoparticles through its pores (5–20 nm size) present in epidermal cell wall of roots (apoplast) (Deng et al. 2014). Larger particles will be blocked so that small particles pass the cell walls results in capillary forces as a result of osmotic pressure and finally reaches endodermis by diffusing through the apoplast (Lin et al. 2009; Deng et al. 2014). In plants, nanoparticles can be uptaken by symplastic pathway through the plasma membrane inner side. Migration of nanoparticles to neighbor cells occurs through 20–50 nm (diameter) plasmodesmata channels (Deng et al. 2014). One more possible way of nanoparticle entry is foliar via pores of stomata and could be translocated to other parts along with roots (Hong et al. 2014). Nanoparticles (silver, zinc oxide, iron oxide, ceria and titania) with huge range of size and composition can interact with plants by means of internalization into leaves (Chichiricco and Poma 2015). The nanoparticles react with organelles of cell and contributes in oxidative stress, metabolic transformations and genotoxicity (Deng et al. 2014). Even though few nanoparticles exposes positivity on one extreme, also urges negative consequences on another extreme. For Example CeO nanoparticles (500 mg/kg) exposed to barley could boost up shoot biomass (300%) but no grain formation was possible (Rico et al. 2015).
3.2 Detrimental Effects of Nanoparticle on Biochemical Traits of Plants
Even though the plant nanoparticle interaction brings some beneficial effects, huge studies are found available in indicating the detrimental effects of nanoparticle towards plants. The detrimental effects upon biochemical traits involves in ROS generation, lipid peroxidation, decline transpiration rate, disruption in mitosis, cell wall breakdown, diminished content of chlorophyll and cutback photosynthesis (Tripathi et al. 2017). Exposure of carbon-based nanoparticles (CNTs, C60) results in cellular toxicity of rice, onion and spinach respectively (Chen et al. 2010; Shen et al. 2010; Begum and Fugetsu 2012). TiO2 exposure produces stress in cucumber (Servin et al. 2013). Exposure of NiO nanoparticles in tomato triggers stress which was followed by mitochondrial and cell damage (Faisal et al. 2013). TiO2 exposure produces chloroplast damage and hence photosynthetic rate of spinach was also decreased. In green peas the chlorophyll is greatly affected by ZnO nanoparticles (Mukherjee et al. 2014).
3.3 Unfortunate Outcomes of Nanoparticles on Plant Morphological Changes
The morphological changes of plants include germination index (germination rate and time), biomass of shoot and root, morphology of root tip, root elongation, etc. (Deng et al. 2014). The phytotoxic nanoparticles includes gold, silver, copper oxide, zinc oxide, carbon nanotubes and alumina which produce detrimental effects on roots and shoots (Ghodake et al. 2011; Begum and Fugetsu 2012; Begum et al. 2012; Burklew et al. 2012; Dimkpa et al. 2013; Deng et al. 2014; Feichtmeier et al. 2015). Exposure of ZnO in soybean plant affects formation of seeds (Yoon et al. 2014). Gold nanoparticles exposure in tobacco plant urges necrosis in tissues (Sabo-Attwood et al. 2012). CNTs inclusion is found to be phytotoxic against cucumber, lettuce and red spinach by decreasing length of roots and shoot, at the same time no unfavourable effects were recognised in soybeans and chilli (Begum et al. 2014). By virtue of nanoparticle absorption by roots, numerous NPs contributes adverse effects to seedling during roots and shoot elongation. Nanoparticle phytotoxicity pertinent to inhibition of growth reveals biomass reduction, decrease in germination and growth of leaf, reduced elongation of root, decreased root biomass, change in root tip morphology, and shoot growth, flowering delay and yield decrease (Tripathi et al. 2017). Silver nanoparticles exposure results in stunted germination of corn and rice (Pokhrel and Dubey 2013; Thuesombat et al. 2014) followed by reduction of mitotic index and fragmentations of chromosomes in onion (Kumari et al. 2009). Growth of rice, soybean, corn and cabbage plants were adversely inhibited by the exposure of ZnO nanoparticles (Lin and Xing 2007; Boonyanitipong et al. 2011; Xiang et al. 2015). Carbon-based nanoparticles like C60 and CNTs urges biomass reduction in zucchini (Stampoulis et al. 2009), followed by delay in flowering and diminished harvest (Lin et al. 2009). TiO2 exposure towards corn brings about inhibition in growth of leaf with damage of DNA damage (Asli and Neumann 2009; Castiglione et al. 2011).
3.4 Genotoxic Effects of Nanoparticles in Plants
Because of tiny size, NPs can migrate into cells and evoke genetic response of plants. Numerous metal nanoparticles like, Ag, CuO, CeO, TiO2, ZnO and CNTs triggers genotoxicity against huge plant varieties (Fava beans, Soybean, Buckwheat, Ryegrass, Radish, Tobacco, Onion) (Kumari et al. 2011; Atha et al. 2012; Burklew et al. 2012; Chichiricco and Poma 2015; Ghosh et al. 2015). Genotoxic effects of nanoparticle comprises mitotic index reduction, fragmented sticky chromosomes, gene alteration, chromosomal aberrations, damage of DNA structure and decline viability of cell (Tripathi et al. 2017). These effects were observed in garlic, onion and buckwheat as a consequence of ZnO exposure (Kumari et al. 2011; Shaymurat et al. 2012; Lee et al. 2013). Exposure of CuO to buckwheat and radish results in genotoxic effects (Atha et al. 2012; Lee et al. 2013). Various chromosomal aberrations (breaking of chromosome and nuclear blebbing) were resulted by titanium oxide nanoparticle exposure (Pakrashi et al. 2014). Accumulation of CNTs in onion plants ascertained both cytotoxic and genotoxic consequences, which includes alteration in morphology of cells, affecting function of mitochondria and membrane integrity, damage of DNA and chromosomal aberrations (Ghosh et al. 2015). CeO nanoparticles causes adverse effects in intake of nutrition along with genetic alterations of wheat, rice and cucumber (Hong et al. 2014; Rico et al. 2014; Zhao et al. 2014).
3.5 Depletion of Growth Nutrients in Plants Due to Nanoparticles
The plants and plant products like fruits are being consumed mainly for its nutrients and minerals. Exposure of nanoparticles could also results in altered nutrient content, flavor of fruit, performance of growth and antioxidant capability (Deng et al. 2014; Petersen et al. 2014; Antisari et al. 2015). Hence, usage of agrichemicals composed of nanoparticles would affect nutrients of various crops like rice, soybean, corn, cucumber and tomato (Rico et al. 2013; Antisari et al. 2015; Zhao et al. 2014, 2015). Numerous metal nanoparticles (TiO, Ag, Co, Fe3O4, CeO2 and Ni) exposure to tomato plants displays depletion of compounds like Mg, P and S (Antisari et al. 2015). Exposure of CeO2 nanoparticles in rice harvest grains resulted in negotiable nutrition values which includes least amount of starch, antioxidants, glutelin, iron, lauric and valeric acid (Rico et al. 2013). Nanoceria exposed cucumber plants would produce fruits with altered Mo micronutrient, sugar, phenolic contents along with fractionation of protein (Zhao et al. 2014). Exposure of nanoceria to corn plant urges decreased yield and curtail calcium translocation to kernals provided by cob (Zhao et al. 2015). ZnO nanoparticles exposure to corn plants produce subtle effects on altered nutrient contents, and reduced photosynthesis as a result of chlorophyll content consequently reduction in yield (49%) (Zhao et al. 2015).
3.6 Transgenerational Effects in Plants by Nanoparticles
Nanoparticles can got concentrated within tissues of roots, seeds, fruits and leaves. Uptake of nanoparticles by seeds has revealed to produce transgenerational effects over few plants (Lin et al. 2009; Wang et al. 2013). The nanoparticles could be disseminated to the progenies of plants through seeds even without exposure of nanoparticles externally. C70 could be found in the rice plants even after second generation as black aggregates adjacent to vascular system of stems and leaf tissues (Lin et al. 2009). The second-generation tomato plants obtained after exposure of ceria nanoparticles to parent plants were found to be uncertain with decrease in biomass, declined transpiration of water and greater ROS amount (Wang et al. 2013). The impact of nanoparticles on plant is given in Fig. 1.
4 Nanoparticles on Humans and Animals
4.1 BioToxicity of Nanoparticles in Humans and Animals
The nanoparticles are inappropriate in some extent that some are beneficial agriculturally, nevertheless those are internalized within crops and toxic towards human and laboratory animals by some extent. The toxicity of nanoparticle on animals relies on their size that helps in entering into the organisms, reach circulatory system, translocation to various organs like brain, kidneys, spleen, liver finally enter cells and organelles (Buzea et al. 2007). Those adverse effects are correlated with inflammation and discrete diseases including cancer. Even though the nanotoxicology is rather a new discipline, plenty of epidemiological investigation on toxicity of environmental nanoparticle towards human are elderly available. Some of the toxic effects of various nanoparticles tested against huge animal models and human cell lines were tabulated (Table 1).
4.2 Factors Affecting Biotoxicity of Nanoparticles—Physicochemical Characteristic
The determination of nanoparticle toxicity confides on the physico-chemical properties like shape, size, composition, porosity, hydrophobicity, surface area, aggregation, magnetic properties and electric charge (Buzea et al. 2007; Li et al. 2015; Silva et al. 2015; Schlinkert et al. 2015; Teske and Detweiler 2015). Same compound derived nanoparticles would exhibit diverse toxicity based on its distinction in size, surface charge and functionalization. Nanoparticles with similar size but with different material composition would also exhibit diverse toxicities obviously. Smaller size nanoparticles will have greater toxicities than the larger ones (Buzea et al. 2007). Simultaneously NPs (Titanium oxide) with same material composition but with varied crystalline forms (rutile and anatase forms) could exerts divergent properties and toxicity. Titania in rutile form (200 nm) would induce oxidative damage to DNA and cytotoxicity in bronchial epithelial cells of human, on the other hand anatase form of titania could not (Gurr et al. 2005). Few NPs displays both hydrophobic and hydrophilic properties (Garcia-Ivars et al. 2015) which are modulated by the employed coating substances (Podila and Brown 2013) such as polyethylene glycol (PEG) provides hydrophilicity for the accompanying nanoparticle (Kettler et al. 2014). Charges of NPs either positive or negative charge is responsible to react with different biological systems (Gatoo et al. 2014; Salatin et al. 2015). For example NPs with positive charge would be attracted towards cell membranes carrying negative charge and results in cellular intake, which couldn’t be made possible by nanoparticles with negative and neutral charge (Kettler et al. 2014). Investigations also revealed that higher charge (positive and negative) imparts increased endocytic uptake mediated by receptors than the nanoparticles with neutral charge (Kettler et al. 2014). Toxicity of nanoparticles confides on internalization within the cells, such that gold nanoparticles with cationic property are toxic than the nanoparticles with anionic property (Goodman et al. 2004).
4.3 Mode of Internalization of Nanoparticles into Humans
By virtue of its tiny size, NPs could be ingested, inhaled or penetrated via the skin. The smaller nanoparticles will have higher accumulation within tissues (Sonavane et al. 2008). Accumulation of NPs within the body sites is resolved by its respective composition and functional groups on surface. By means of the gastrointestinal and respiratory systems, the nanoparticles could hastily reaches circulatory and lymphatic system respectively (Landsiedel et al. 2012). It was revealed from various studies that the nanoparticles inhaled would accumulate in the lungs, some of them could reach alveoli based on their respective size and physicochemical properties, could also be systemic by translocating to other organ. These nanoparticles were found available in various parts like heart, brain, liver, spleen, thyroid, kidney, colon, bones along with lymphatic system and circulatory system (Johnston et al. 2010; Khlebtsov and Dykman 2011; Landsiedel et al. 2012; Anderson et al. 2015; Bruinink et al. 2015; Davidson et al. 2015; Geiser and Kreyling 2010; Gosens et al. 2015). Various types of NPs were found in the blood of many diseased patients (Gatti and Montanari 2006). Those nanoparticles combine with the plasma present in the circulatory system and results in the formation of protein corona which determine its toxicity and translocation. Later on, the nanoparticles reach and thereby acquire within various organs and tissues of heart, brain, liver, kidney, spleen, lymph nodes, bone marrow (Landsiedel et al. 2012; Sonavane et al. 2008).
The NPs enter through ingestion reach the gastrointestinal tract and are partially eliminated through feces, few get absorbed and found systematically (Hillyer and Albrecht 2001). It was evident from studies of animal model (in vitro and in vivo) that the nanoparticles could pass the placenta and reach fetus so as resulting in detrimental effects to pregnancy and fetus (Melnik et al. 2013; Semmler-Behnke et al. 2014; Snyder et al. 2015).
4.4 Cytotoxicity of Nanoparticles Towards Animals
Gold nanoparticle cytotoxicity depends on cell specificity and its coating upon surface respectively (Cheng et al. 2013; Schlinkert et al. 2015). These NPs internalized within the cells as a result of surface functions and by locations in mitochondria and lysosomes (Cheng et al. 2013), nuclei (Ojea-Jimenez et al. 2012) and vacuoles (Khlebtsov and Dykman 2011). In vivo studies of NPs in macrophages (spleen and liver kupffer cells) shown severe inflammation and liver cells apoptosis (Cho et al. 2009). Overexposure of silver nanoparticles in the form of wound dressings or drugs to humans undergo a condition called argyria (blue-gray discoloration of skin) associated with adverse toxic effects on liver (Christensen et al. 2010; Hadrup and Lam 2014). Exposure of silver nanoparticles would results in cardiac dysfunction in chicken, malformation of heart in fish and formation of thrombus in rats (Yu et al. 2016). Some studies represented that lungs and liver are the main targets of AgNPs exposure (Sung et al. 2008; Takenaka et al. 2001). Exposure of AgNPs on rat liver cells deplete antioxidant glutathione, decreased mitochondrial membrane potential and elevated ROS mediated by oxidative stress of liver cells (Hussain et al. 2005). Titanium oxide nanoparticle exposure develop arrhythmia in rats because of their direct contact with cardiac tissue (Savi et al. 2014). Titanium NPs on rodents heart tissue results in myocarditis, arrhythmia, vascular dysfunction, cardiac damage with dysfunction, and some inflammatory responses (Yu et al. 2016). Degradation of DNA is possible with generation of oxygen species after copper nanoparticle exposure. As a result of in vivo experiments using mice, exploration of copper NPs translocate to organs like spleen, kidney and liver and finally results in inflammation of the respective organs (Magaye et al. 2012). Affirmatory effects of cerium oxide NPs on various cell lines would results in reactive oxygen species (ROS) and apoptosis (Mittal and Pandey 2014; Gagnon and Fromm 2015). Magnetic nanoparticles (Fe, Co and Ni) can be used in vivo imaging for diagnosis, more liable for aggregation, and finally results in inflammation followed by immune responses (Markides et al. 2012). Intravenous administration of ultrasmall supermagnetic iron oxide nanoparticles (USPION) in mice boost up blood clot formation followed by cardiac oxidative stress (Nemmar et al. 2016). Elicitation of nickel nanoparticles produce severe cytotoxic effects like oxidative stress which was followed by cell death (Magaye et al. 2012). Silicon nanoparticles could produce adverse cytotoxic effects on diverse human cell types like epithelial cells, platelets, microvascular endothelial cells, umbilical vein endothelial cells and aortic vessel cells (Yu et al. 2016). Exposure of carbon nanotubes (CNTs) in rodents produce consequences like thrombus formation, damage of placenta vessel, vasorelaxation, endothelial and cardiac dysfunction (Yu et al. 2016). Cytotoxic effects were observed in huge range of cell types like smooth muscle cells, blood cells, aortic endothelial cells, umbilical vein endothelial cells and microvascular endothelial cells of human (Yu et al. 2016). Even though, lack of action on cell viability or migration was observed, the platinum nanoparticle (Pt NPs) exposure produce some extent of activity in triggering toxicity towards primary keratinocytes and diminished metabolism of cells (Konieczny et al. 2013). Cytotoxic effects of Pt NPs resulted in accumulation in lysosomes and liberation of Pt2+ (Asharani et al. 2010).
4.5 Toxicity of Nanoparticles in Organ Development
Exposure of titanium oxide nanoparticle towards animal models would results in reduction of sperm production, alteration of neurobehaviour, abnormality in brain development of fetus, small fetuses, deformation of fetus and mortality (Savi et al. 2014).
4.6 Immunogenic Responses of Nanoparticles
Accumulation of AgNPs in the organs of immune system were followed by multiple organ (thymus, spleen, liver and kidney) damage (Wen et al. 2017). The reduced cell viability of alveolar macrophages and epithelial cells of lungs are possible on AgNPs exposure (Soto et al. 2007) Oxidative stress along with alveolar macrophage toxicity was observed in AgNPs by Carlson et al. (2008). Titanium oxide exposure would cause toxicity which comprises effects of immune system (Savi et al. 2014). Exposure of ZnO NPs on rats and mice results in cardiac inflammation and apoptosis (Yu et al. 2016). Long term exposure of cobalt NPs were accompanied with immune system related health effects, skin, lungs and thyroid gland (Simonsen et al. 2012).
4.7 Genotoxic Effects of Nanoparticles
Injection of gold nanoparticles on rat samples (spleen and liver) produce changes in gene expression and results in lipid metabolism, defense response, detoxification, circadian rhythm and cell cycle (Balasubramanian et al. 2010). Genotoxic effects, because of chromosomal breakage is made possible by the exposure of nanoparticles to human (Wen et al. 2017). Silver nanoparticle exposure in chicken cause genotoxic effects (Yu et al. 2016). Intraperitoneal injection of AgNPs in mouse results in cytotoxic effects upon brain which are mediated by apoptosis, neurotoxicity with oxidative stress and change in genetic expression (Rahman et al. 2009). In addition to cytotoxic effects, some genotoxic effects were also observed in numerous cell lines as a result of titanium dioxide nanoparticles exposure (Gurr et al. 2005; Coccini et al. 2015; Yu et al. 2016). Zinc nanoparticle exposure to mice and rats were more probable to produce DNA damage (Yu et al. 2016). Administration of USPION intravenously to mice promote DNA damage (Nemmar et al. 2016). Exposure of nickel nanoparticle would bring about genotoxic effects as a result of cytotoxicity (Magaye et al. 2012). Alike production of cytotoxic effects by silicon nanoparticles, genotoxic effects were also possible on human cell types like, epithelial cells, aortic vessel cells, platelets, microvascular endothelial cells and umbilical vein endothelial cells (Yu et al. 2016). Genotoxic effects were observed followed by cytotoxic effects in huge range of cell types like smooth muscle cells, blood cells, umbilical vein endothelial cells, aortic endothelial cells and dermal microvascular endothelial cells of human (Yu et al. 2016). Exposure of platinum NPs displayed more detrimental effect on the stability of DNA (Konieczny et al. 2013).
4.8 Tumorigenesis in Animals by Nanoparticles
Nanoparticle could be vital for greater than 6 months within the body (Lin et al. 2015). Persistence for a longer time in the body would cause tissue inflammation injury and finally results in various diseases including cancer. The metallic nanoparticles residence in tissues aids tumorigenesis (Sighinolfi et al. 2016). Various studies are available to demonstrate the accumulation of nanoparticles within the tissues of patients infected with numerous diseases like pulmonary embolism, deep vein thrombosis, Hodgkin’s lymphoma, prostrate cancer, renal failure, colon cancer, ulcerative colitis, emphysema, lung cancer, liver necrosis, asthma, stroke and Crohn’s disease (Ballestri et al. 2001; Gatti and Rivasi 2002; Gatti 2004; Gatti and Montanari 2006; Iannitti et al. 2010; Roncati et al. 2015a, b). Exposure of copper dust or fumes on copper smelter workers would expand cancer risk (Magaye et al. 2012). Dermal exposure and inhalation of magnetic nanoparticle (copper and nickel) results in cancer, lung fibrosis and skin allergies (Magaye et al. 2012). A detailed study on toxicity of CNTs revealed that its exposure would result in fibrosis and granulomas as consequences of carcinogenic and genotoxic effects (Aschberger et al. 2010).
5 Biohazards of Nanoparticle on Environmental Concern
The nanoparticles and their products enter the environment inevitably by means of washing, recycling and disposing (Kohler et al. 2008). The natural ecosystems are contaminated directly by the discharge of waste water and powder nanoparticles into the atmosphere. Unintentional release of AgNPs also results due to the activities like sampling, leaking and accidental release during transportation (Yu et al. 2013). Elemental silvers are found available in various forms as native silver (Leblanc and Lbouabi 1988; Lu et al. 2012) and as blends with metals like gold (Electrum) (Saunders et al. 2008; Denditius et al. 2011). Recently, AgNPs are extensively used in our day to day life with disinfectant sprays, outdoor paints, odour free socks, antimicrobial plastics and textiles. These nanoparticles reach the environment through scrapes, ageing of the materials and periodic washing of the materials. Liquid products like sprays and disinfectant are very rapid in entering the environment than the particles fixed to a solid cast like textiles and paints. The nanoparticles reacted to the sewage treatment plants could be used as fertilizers for agriculture land so as to reach the terrestrial system or groundwater system as leachate. Once the silver nanoparticles get released into the atmosphere, it could transport, disseminate and alter into various forms. The humans are exposed to nanoparticles through breathing, skin contact or eating. Environmentally exposed nanoparticles are associated with several neurodegenerative diseases (Alzheimer’s disease, dementia and Parkinson’s disease) (Calderon-Garciduenas et al. 2016; Chin-Chan et al. 2015; Gonzalez-Maciel et al. 2017). It was evident from the recent studies that the environmental polluted nanoparticle can translocate to the brain (adults and child) then enter cells and organelles and finally results in cellular damage with neurotoxicity (Gonzalez-Maciel et al. 2017). The exposure of AgNPs are manifested to affect huge number of aquatic and terrestrial habitats. They invade the embyos of zebrafish and results in growth interruption and abnormality. Acute and chronic studies deals with biological toxicities available based on organisms like algae, cladoceran and freshwater fishes. Over all, some iron nanostructures (iron oxide, ferrihydrite, lepidocrocite, hematite, maghemite, magnetite) are also naturally available in aquatic and terrestrial ecosystem (marine, rivers, lakes, springs, soils and sediments) and could possibly results in cytotoxic effects accompanied with ROS (Guo and Barnard 2013).
6 Hazardous Effects of Nanoparticles Towards Aquatic Organisms
The toxicity of various species in the aquatic system were studied by various researchers, among them the dominant species is fish followed by crustaceans, crabs and algal species. Their respective growth, organ development and reproductive behavior which were analysed by various studies and were tabulated (Table 2). The results revealed their lethality, behavioural change, toxicity and related stress. The environmental impact of a nanoparticle resides on various physical, chemical and biological parameters like shape, size, surface structure, surface charge, chemical composition, solubility aggregation and dispersion of nanoparticles (Navarro et al. 2008).
6.1 Cytotoxic Effects of Nanoparticles Against Algae
Nanoparticles are curious because of their high surface which can adsorb to pollutants, thereby alters its bioavailability along with the pollutants, and hence toxic to algae. Few heavy metals (Zn, Co, Cu, Ni, Pb and Cd) possess some detrimental effects towards algal growth, cell division, photosynthesis and primary metabolites elimination. The cytotoxicity is influenced by factors responsible for its conceivable mechanisms. Exposure of TiO2 nanoparticles would entraps the algal cells thereby reducing the availability of light and subsidise toxicity to the algal cells (Aruoja et al. 2009). When compared with dark conditions, greater cytotoxicity was observed under light conditions. Scenedesmus obliquus produce serious ROS and increased membrane permeability while exposed to TiO2 nanoparticles (Cherchi et al. 2011). Hazeem et al. (2016) reported that ZnO nanoparticles impose obscure effects upon marine algae thereby affecting its growth and chlorophyll a content during early stages of its growth respectively. Exposure of CuO nanoparticles produce adverse impacts on morphological, biochemical and physiological algae processes. The production of ROS, oxidative stress results in biomolecules (protein and lipids) damage, and finally reduced activity of glutathione activity was also happened (Melegari et al., 2013, Babu et al. 2014). As the concentration of CuO nanoparticles increased, metabolic activity of the cells were also decreased (Melegari et al. 2013) followed by damage of photosynthetic pigments in the presence of light meanwhile alters photosynthesis (Gouveia et al. 2013). The extent of DNA damage increases with higher concentration of CuO nanoparticles (Babu et al. 2014). Moreover, Cu NPs were found available in the cell membranes of algal cells at various sites while investigating the lipid peroxidation of cell membranes (Manusadzianas et al. 2012; Melegari et al. 2013). The GO exposure towards Raphidocelis subcapitata brought some adverse effects like oxidative stress and membrane damage (Nogueira et al. 2015). The pristine graphene exposure will results in inevitable disruption of cell wall and cell swelling (Pretti et al. 2014). The toxicity of nC60 nanoparticle was contributed by absorption and aggregation of the particles over the algal surface thereby hindering Mg2+ channels and triggering photosynthetic toxicity (Tao et al. 2016). The vital factor responsible for Au nanoparticle toxicity are bioavailability and biotoxicity. The electric charge present on its surface, for example positive charge functional group can employ toxicity on algae as it combined with the algae. The secondary factor that assimilate toxicity is its smaller hydrodynamic particle size (Garcia-Cambero et al. 2013). The exposure of AgNPs towards algae results in toxic effects including membrane adhesion, alteration in permeability and ion transport thereby expanding the porosity of cell, interruption in phosphate management of cell and DNA synthesis inhibition and ROS formation (Klaine et al. 2008). After exposure of AgNPs, deformation of algal cells from spindle to round was happened, ultimately results in cell lysis and collapse. The dose of the AgNPs is responsible for the severity of toxicity and algal viability, even more ionic silver exhibits extreme algal toxicity than AgNPs (He et al. 2012).
6.2 Nanoparticles Effects on Terrestrial Species
The released nanoparticles could be deposited in the terrestrial ecosystem like sewage and soil matrix thereby absorbed so as to interact soil organisms finally results in toxic effects. The routes of nanoparticle exposure includes nutrition absorption, body surface contact and through water. As per the observation of Yin et al. (2011) AgNPs coated with gummi arabicum inhibited the growth and morphological damage was triggered on Lolium multiflorum. Few terrestrial animals like nematodes and earthworms were chosen as the models for toxicity evaluation of AgNPs in soil due to high permeability of their skin. Exposure of AgNPs to Eisenia fetida earthworm resulted in growth and reproductive toxicity (Shoults-Wilson et al. 2011). Feeding Acheta domesticus (House cricket) with nanodiamond supplemented diet affected the insect development with oxidative damage followed by feeding disturbances (Karpeta-Kaczmarek et al. 2018). Some soil microbes which were exposed by AgNPs are found to be extremely sensitive and toxic.
6.3 Cytotoxic Effects of Nanoparticles Against Beneficial Microbes and Protozoa
Microorganisms are the unique nitrogen fixers and animal degraders found in nature, by the mean time these microbes were located at the end of the food chain to complete the cycle. Silver nanoparticles (AgNPs) has been acknowledged because of its antimicrobial (antibacterial and antifungal) activity so as to be used as agrochemicals extensively. Correspondingly, the AgNps sustenance in soil would have consequence upon beneficial microbiota of soil like nitrogen fixing bacteria, consecutively affects physicochemical characteristics of both plants and soil (Anjum et al. 2013). Additionally the AgNPs interact with the bacterial cells and are toxic that finally results in death of microbes like E. coli (Lok et al. 2006). Exposure of inorganic nanoparticles like TiO2, SO2 and ZnO produce toxic effects upon bacteria which found to increase in the presence of light (Lovern and Klaper 2006). Death of microbes resulted by the cell membrane damage are made possible by the exposure of carbon nanomembranes (CNMs), could also vitally confides upon harmness to ecosystem, human health and finally resides in loss of biodiversity (Chen et al. 2017). Exposure of TiO2 nanoparticles to Saccharomyces cerevisiae under dark condition results in toxic effect (Kasemets et al. 2009), whereas TiO2 exposure towards E. coli and Bacillus subtilis results in growth inhibition (Erdem et al. 2015). CNMs also possibly induce ROS associated with lipid peroxidation, DNA damage, protein denaturation and finally cell death. The cells of protozoa could able to absorb carbon nanotubes resulting in accumulation within the mitochondrial cells (Zhu et al. 2006).
7 Future Perspectives
The experimental data which reveals the possible interaction between plant root and the nanoparticle is needed. Since the nanoparticles are widely consumed by human, their physical, chemical and biological interactions have to be studied keenly. Hence more prudential idea about interactions of nanoparticle with cells and their respective toxicity will be recognized. There is no detailed data regarding the consequences resulting from the chronic exposure of the nanoparticles to both environment and living beings.
8 Conclusion
Even though the utilization of nanoparticles has elevated in consumer and economical aspects, some detrimental consequences were also being faced by plants, animals, human and environment. This chapter explored the fragmentary views of discrepancy in practicing nanoparticle based on its toxicity and environmental hazards. If the nanoparticles are used as agrichemicals to boost up soil fertility some phytotoxic effects were also ascertained, which results in various diseases related to human and animals. Over exposure of nanoparticles to the environment will also pose catastrophic risks to the organisms residing in the environmental habitat.
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Authors thanks the financial support given by RUSA – Phase 2.0 grant sanctioned vide Letter No. F.24- 51/2014- U, Policy (TNMulti-Gen), Dept. of Edn. Govt. of India, Dt. 09.10.2018.
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Ananthi, V. et al. (2020). An Overview of Nanotoxicological Effects Towards Plants, Animals, Microorganisms and Environment. In: Krishnan, A., Chuturgoon, A. (eds) Integrative Nanomedicine for New Therapies. Engineering Materials. Springer, Cham. https://doi.org/10.1007/978-3-030-36260-7_5
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