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July 1, 2018 - 11:54

Nanotechnology has advanced exponentially over the past two decades, with nanoscale materials being exploited in many applications and in several disciplines, including industry, science, pharmacy, medicine, electronics, and communication products. Vance et al. reported a 30-fold increase in nano-based products between 2011 and 2015 (Figure 1) and an estimated global market of over $1 trillion in 2015. Metal nanoparticles (NPs) (specifically, carbon and silver NPs) represent the largest and fastest growing group of NPs. Human and environmental exposure is already occurring and is predicted to increase dramatically.

Fig. 1: Nanomaterial growth trend 2010–2015

Nanomaterials (NMs) are generally defined as substances having particles with at least one dimension of 1–100 nm in length. Their novel physical and chemical characteristics have made them useful in several applications; however, these very properties can be potentially toxic. Once introduced into aquatic ecosystems, the fate and toxicity of NPs and their uptake by aquatic organisms depends on several factors. Both the properties of a NP (such as size, shape, and coatings) and water chemistry (such as dissolved organic carbon, ionic strength, pH, temperature) will largely influence the extent to which NPs will either remain in suspension, partition to dissolved organic carbon in the water column, form aggregates, or adsorb to suspended particles. In aquatic organisms, the accumulation of NPs is dependent on both the uptake and the elimination of the NP out of the organism. These processes also regulate the bioaccumulation (and bioavailability) of NPs.

Nanotoxicology is a branch of bionanoscience, which deals with the study and application of the toxicity of nanomaterials. Nanomaterials, even when made of inert elements such as gold, become highly active at nanometer dimensions. Nanotoxicological studies are used to determine whether and to what extent these properties may pose a threat to the environment and to human health.

Aquatic ecosystems are progressively coming under pressure due to the presence of emerging anthropogenic contaminants, including NMs, posing health hazards to inhabitant organisms. In recent years, increasing data demonstrated that NPs could induce toxicity and genotoxicity under a variety of exposure scenarios. An accepted mechanism by which NPs may induce cytotoxicity is considered to be through the induction of reactive oxygen species (ROS), which can induce oxidative stress, which in turn may lead to cytotoxicity, DNA damage, and other effects.

Physical and chemical properties of NMs influencing their toxicity

The behavior of NPs in various environmental matrices is complex and involves several processes. Properties of NMs are unique and different from conventional materials. Properties such as (1) particle size, (2) surface area and charge, (3) shape/structure, (4) solubility, and (5) surface coatings are known to affect NP toxicity.

Owing to their small size, NMs have unique physical and chemical characteristics such as magnetic, optical, thermal, mechanical, electrical properties which make them suitable in several applications including in medicine, electronics, and energy production, and in several consumer products. However, these very properties have the potential to affect humans and the environment adversely. NPs can easily penetrate cell membranes and other biological barriers into living organisms causing cell damage. Studies reporting increased toxicity of NPs when compared to their larger bulk particles have led to a generally assumed hypothesis that NPs are more potent in causing damage. Lankvel et al. reported the significance of particle size of Ag NPs, reporting size-specific tissue distribution and size-specific toxicity. Scown et al. reported the lowest aggregation potential for the smallest Ag NPs (i.e., 10 nm vs. 35 and 600–1600 nm) and was most highly concentrated in the gills and liver. Gaiser et al. studied the acute and chronic toxicities of nano and bulk Ag and CeO2. Reported mortality rates for Ag and Ag NP were as follows: micro-Ag at 0.1 mg/L was 13% and at 1 mg/L was 80%, while for Ag NP at 0.1 mg/L was 57% and at 1 mg/L was 100%.

Routes of exposure in the aquatic environment

Due to the surge in nanotechnology, there have been significant increases in the number of various NPs released into the aquatic environment. Figure 2 provides a summary of the possible routes in a typical aquatic environment to nanoparticles, potential interactions, and the possible clearance routes. Aquatic ecosystems are susceptible to environmental contamination since they are at the receiving end of contaminants, particularly from runoff sources. Identified sources of NPs in the aquatic environment include production facilities, production processes, wastewater treatment plants, and accidents during the transport. In addition, aquatic ecosystems are known to sequester and transport contaminants, including NMs. Baun et al. showed that NPs may adhere to algae which may then be consumed by filter-feeders and transfer to higher trophic levels. In the aquatic environment, NPs may aggregate thus reducing the NPs available for direct uptake in the aqueous phase by aquatic organisms. However, aggregated NPs may settle into sediment thereby posing a threat to benthic organisms. In the aquatic environment, NMs are generally associated with sediments. Sediments and soil represent porous environmental matrices which typically have large specific surface areas.

Fig. 2: Possible pathways of nanoparticles in the aquatic environment


The main questions scientists are currently facing are: what is the mechanism of toxic action of nanoparticles; how does the reactive surface of nanoparticles interact with “wet internal environment inside the body”; and what is the relative contribution of particle size versus particle composition in the overall toxicity of nanoparticles. Definitive answers to all these questions are currently lacking although research is underway in a number of centres. Although the chemical composition of nanomaterials is known, rearrangements, for example, of carbon into new polymeric structures, or, similarly, the restructuring of metal oxide or crystalline lattice, are worthy of toxicological considerations.

The experiences with the different forms of silica and asbestos have taught us that the physical/ chemical properties of materials can be very important determinants of the toxicological potential. The very surface area and quantum chemistry effects that the nanosciences are exploring and hope to manipulate, are also known to be important in determining the manner in which biological systems function and interact with the physical world. The multitude of available in vitro studies dealing with the mechanism of nanoparticle uptake in different cell types as well as the few studies on in vivo uptake and nanoparticle distribution in animal models demonstrate that there is no single common uptake mechanism for nanoparticles. The upper size limit for the toxicity of nanoparticles (ultrafine particles) is not fully known, but is thought to lie between 65 nm and 200 nm. In vitro studies performed on cell cultures have confirmed the increased ability of nanoparticles to produce free radicals which can cause cellular damage. Generation of reactive oxygen species (ROS) upon exposure of cells to particulate matter is nowadays considered a major contributor to nanoparticle toxicity. The cell membrane, mitochondria, and cell nucleus are considered relevant for possible nanoparticle-induced toxicity.

In the light of current knowledge, it seems that the size effect is considerably more important for nanoparticle toxicity than the actual composition of the material. In contrast, in vivo pulmonary inflammation and cytotoxicity studies on rats show that TiO2 toxicity does not depend on particle size and surface area. Over the last five years the number of papers on the ongoing work in nanotoxicology has increased exponentially. However, it is still not possible to draw any common conclusion about how nanoparticles interact with biological systems. In different in-vivo and in-vitro studies, the authors find both dose-dependent and dose-independent response to nanoparticles. The type of response is obviously related to the measured parameters. In the same study, some measured parameters may be dose-dependent, while others may not. It is interesting and worth mentioning that the highest doses do not necessarily provoke the most pronounced response, neither in in-vitro nor in in-vivo studies.


Risk assessment is the evaluation of scientific information on the hazardous properties of a variety of agents, the dose-response relationship, and the extent of exposure of humans or environmental targets to these agents. The product of risk assessment is a statement about the likelihood of exposed humans and the ecosystem with all its components being harmed and to what degree (risk characterization). The following key aspects of risk assessment are addressed, as they relate to nanomaterials:

a) Identification of chemical and physical properties: This is an important first step in assessing their risk. The diversity and complexity of nanomaterials makes chemical identification and characterization more difficult than with other chemicals. A broader spectrum of properties will be needed to sufficiently characterize a given nanomaterial, evaluating the hazard and assess the risk.

b) Environmental fate: Fundamental properties concerning the environmental fate of nanomaterials are not well understood. Models used to assess the environmental fate and exposure to conventional chemicals are not applicable to intentionally produced nanomaterials. Depending on the relevance of chemical properties or transformation, new models may have to be developed to provide estimations for new materials. However, a certain amount of reliable experimental data must be acquired before the environmental fate, transport, and multimedia partitioning of nanomaterials can be effectively modelled.

c) Environmental detection and analysis: The challenge in detecting nanomaterials in the environment is compounded not only by the extremely small size of the particles, but also by their unique physical structure and physico-chemical characteristics. The variety of physical and chemical properties can significantly affect the extraction and analytical techniques that can be used for the analyses of a specific nanomaterial.

d) Human and ecosystem exposure: Human and ecosystem exposure account for a series of events beginning with external mechanisms that make a chemical / nanoparticle available for absorption or other mode of entry and ending with the chemical or its metabolite reaching the target organ, depending on the nature of the chemical and route of exposure.

e) Human and ecosystem effects: Assessing nanomaterial toxicity is extremely complex and multifunctional, and is potentially influenced by a variety of physico-chemical properties of nanoparticles. At the moment, there is a significant gap in our knowledge of the environmental, health and ecological implications associated with nanotechnology. However, an exponential increase in scientific papers over the last five years reflects the ongoing work and the importance of this area.

A few known toxic effects of nanomaterials

  1. Metal Oxide Nanoparticles

    After extensive investigation, TiO2 nanoparticles were introduced as antimicrobial particles and can be used as a coating material for medical equipment because of their antimicrobial and mechanical properties. TiO2 can accumulate some types of oxygen, the same as hydroxyl radicals and hydrogen peroxide, which has been done by oxidation and restoration under light. The oxygen comes into contact with UV rays, then a photo catalyst produces antimicrobial features which kill all bacteria with endotoxins which, in turn, have side effects in organisms. 

  2. The results showed that the toxicity of ZrO2 and Al2O3 particles (d = 500–700 nm) increases more than TiO2 particles (130–180 nm). Al2O3 coated with TiO2 particles have shown the same toxic effects. Dendritic TiO2 has shown higher toxicity than other forms. The toxicity of ionic metals and other chemical materials differs among cells. The larger particles tend to show greater toxicity than the smaller particles. For example, the larger TiO2 particles cause a higher prevalence of the H-thymidine component than human monotypic macrophages. ZnO nanoparticles with a diameter of 500 to 3000 nm were placed on human fibroblasts for 24 hours. They were stained by hematoxin/eosin, which showed the extent of toxicity; the dead cells, which had been separated from the bottom of the glass, were not colored and the living cells still adhered and absorbed color. A digitizer was used to estimate the colored zone. The cells exposed to Al2O3, TiO2, Fe2O3, Fe3O4, CO2O3, NiO, Ga2O3, SnO, SnO2, and HgO, showed no toxic effect. The results acquired from studies on ZnO, CuO, Cu2O, Cr2O3, and Ag2O show that these particles have toxic effects.

  3. Silver

    The antimicrobial effect of silver-coated surfaces has been studied with 16 types of bacteria. Silver nanoparticles are used in medical design, especially in dentistry. For example, nanosilver crystals are used in bandages as antimicrobial agents, but the use of silver nanoparticles depends on counteracting their positive (antimicrobial effect) and negative (cellular toxicity) effects. In one study, it was observed that nanosilver (12 nm) kills E scherichia coli.

  4. Zinc oxide (ZnO) nanoparticles

    ZnO acts as an effective UV filter when used in sun creams and textiles. Some animal studies and autoradiography have shown that ZnO nanoparticles penetrate into the skin of rats and rabbits. Particles with a diameter of 50 to 100 nm can penetrate the skin because of the intracellular space of the corneum stratum, which is about 100 nm and the distance between the two layers is 0.5 to 1 nm. During inhalation, the particles enter the deep zones of the lung where they are surrounded and excluded by macrophages before epithelial damage. The particles can attach to the epithelium (causing inflammation) and the entrance to the interstitium where they have chronic effects on cells and have the ability to move to the lymphatic nodes.

  5. Fullerene Toxicity

    C60 was first discovered by Korto in 1985, who said that C60 has 20 dimensions in different situations and is composed of apexes and 20 faces. Some features of C60 show that it has potential for use. For example, the first use of C60 has been in optics and conductors. Also, it is used to produce various sanitary products such as creams. Research has proved the antioxidative properties of C60. In 1998, Kamat et al described lipid oxidativity by C60 using the microorganisms of the liver. The study showed that changed fullerene can be toxic, but this toxicity depends on its group factors, which is not a feature of fullerene. Fullerenes can be used in drug delivery systems. The preparation methods for fullerene solution are very important. To prepare this solution, fullerene must first be dissolved in polar solvent, which is able to be dissolved in water. For example, scientists use tetrahydrofuran. The quick separation of organic solvent from aqueous fullerene solution is impossible. In fact, watery solution causes toxicity. In one new study, the researchers investigated the effects of these materials on fish, and described the fullerene antioxidative effect. Cerebral damage could occur due to respiratory medicines such as D-ethyl ether. Tetrahydrofuran has an ether-like effect and is very toxic. In fact, tetrahydrofuran caused cerebral damage, but fullerene had no such effects.

  6. Carbon Nanotubes

    Carbon nanotubes have a seamless graphite cylinder, which has featured in a number of studies, especially in medical science, it is also interesting to study because of its paradoxical effect on the body. Carbon nanotubes tend to twist in the form of a rope, which can be a problem (especially in the lungs). Nanotubes are structures that may behave as nanoparticles or fibres. For example, lung toxicity will occur at high doses of single or multiple-wall carbons, but if their amount and dose are low, inflammation will occur in the lungs. Results have shown that carbon nanotubes at high dose are toxic for organisms, and accordingly, health scientists have defined them as dangerous and suggested manipulation of the nanoparticles. One way to reduce the toxicity of carbon nanotubes is coating or functionalization. Functionalization can affect the properties of the carbon nanotubes, especially their toxicity.

  7. Metal based nanoparticles

    (NPs) are a prominent class of NPs synthesized for their functions as semiconductors, thermoelectric and electroluminescent materials. Biomedically, these antibacterial NPs have been utilized in drug delivery systems to access areas previously inaccessible to conventional medicine. With the recent increase in interest and development of nanotechnology, many studies have been performed to assess whether the unique characteristics of these NPs, namely their small surface area to volume ratio, might negatively impact the environment upon which they were introduced. Researchers have since found that many metal and metal oxide NPs have detrimental effects on the cells with which they come into contact including but not limited to DNA breakage and oxidation, mutations, reduced cell viability, warped morphology, induced apoptosis and necrosis, and decreased proliferation. Metal Oxides such as copper oxide, uraninite, and cobalt oxide have also been found to exert significant stress on exposed DNA.


According to some estimates, nanotechnology promises to far exceed the impact of the Industrial Revolution and is projected to have become a US $ 1 trillion market by 2015. The importance of nanotechnologies to our wellbeing is beyond debate, but its potential adverse impacts need to be studied all the more. Nanotoxicology as a new discipline should make an important contribution to the development of a sustainable and safe nanotechnology. An improved understanding of the risk factors related to nanomaterials in the human body and the ecosystem will aid future development and exploitation of a variety of nanomaterials. Issues related to new nanoparticles are in the headlines due to the fear of their escaping into the environment. In fact, we have lived with sub-micron sized particles around us forever. The introduction of man-made versions has just brought to light the fact how little we know about their toxic effects. Awareness is growing about the need to develop an infrastructure for characterizing and measuring nanomaterials in complex matrices and for developing reference materials, both for calibration of instruments used for assessing exposure and dosimetry, and for benchmarking toxicity tests. The public expects that new or emerging technologies meet higher safety requirements than tried and tested technologies. Failure to meet these requirements may result in public fear or even rejection of nanotechnology-based products, which often essentially improve the quality of life of individuals.

“This article is authored by Dr. Mangalam Ramanathan, Chairperson & Professor, Department of Chemistry, School of Arts and Sciences, Amritapuri”

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