CHAPTER 14

Potential Risk of

Nanotechnology.

• Azmi Bin Hassan• Mohd Nazih Bin Jaafar• Mohd Farid Bin Saiman• Mohd ‘Azzim Bin Nordin• Mohd Faiz Bin Mohd Fuad• Mohd Fikri Bin Omar• Mohd Azamudin Bin Abdul Aziz

GROUP MEMBERS

AGENDA

Introduction• Nanotechnology– Nanotechnology is the understanding and control of

matter at dimensions of roughly 1 to 100 nanometers– Nanotechnology involves imaging, measuring, modeling,

and manipulating matter in this scale• Nanotechnology may be able to create many new materials

and devices with a vast range of applications, such as in medicine, electronics, biomaterials and energy production.

• Humans are exposed to airborne nanomaterials in daily life, such as nanoparticles found in smoke, drugs, paints, cosmetics, soaps, shampoos, detergents, sunscreens, tennis rackets, video screens, coatings, catalysts, concrete.

3 WAYS NANOMATERIALS

UPTAKE BY HUMAN BODY

1. Respiratory System 2. Skin

3. Ingestion

Exposure through respiratory system

Inhalation of nanoparticles leads to deposition of nanoparticles in respiratory tract and lungs.

Caused lung-related disease. E.g. asthma, bronchitis, lung cancer, pneumonia etc.

Translocation of nanomaterials therefore could lead to brain.

Exposure through skino Nanoparticles may penetrate into sweat glands

and hair follicles.o Skin exposure to cosmetics, sunscreens and dusts

resulted in accumulation of nanoparticles.o Baroli et al. reported that metallic nanoparticles

smaller than 10nm could penetrate the hair follicle and stratum corneum and sometimes reach the viable epidermis.

o However, metallic nanoparticles unable to permeate the skin.

Exposure through Ingestion Exposure of nanomaterials into gastrointestinal

tract can occur after uptake of daily food, drinks and medicines.

Nanoparticles absorbed by any means can cause cytotoxicity effects.

Cytotoxicity means that nanoparticles prevent cell division, hinder cell proliferation, damage DNA and biological system and lead to cell death by biological process called apoptosis.

Apoptosis is a process of deliberate cell self-destruction in an organism.

A size dependent study of copper on mice was carried by chen etc al. It show that toxicity increase as the size of copper decrease.

Quantum dots offer surface manipulation and also show potential benefit for biomedical research.

Nanoscale contrast agents show potential applications in magnetic resonance (MR) molecular imaging for clinical diagnosis.

Nanoparticles of cadmium telluride (CdTe) exhibit strong fluorescence that could be used in solid state lighting and biological probing.

Carbon nanotubes used for drug delivery to specific target such as tumor cells. Nanotubes filled with magnetic nanoparticles help in transporting medicine to target.

The biocompatibility of such nanomaterials remains questionable due to their adverse effect on human health.

• A wide variety of nanomaterials, such as a very wide variety of man-made nanostructured materials such as

a. Metallic nanoparticlesb. Quantum dot.c. Fullerenesd. Carbon nanotubes

• Are being used for industrial applications in coatings, cosmetics, pharmaceutical, and biomedical products.

• Recent studies have shown that nanostructured materials impose significant risks to human health.

• Nanoparticles, being smaller in size (1–100 nm), can deposit within the respiratory tract during inhalation.

• Once in the lungs, these nanoparticles start interacting with different biological systems.The inhaled nanoparticles may have toxic effects and could lead to lung diseases.

• For example, Amorphous silica is an important material for its applications in biomedical research because it can be easily produced at low cost .

• But, few reports have recently appeared showing that amorphous silica may be toxic at relatively high doses. Comparatively, a silica-chitosan nanocomposite causes less inhibition in cell proliferation and less membrane.

• That means, the cytotoxicity of silica to human cells could be reduced by using silica with chitosan.

• For Fe3O4, Al2O3, and TiO2 had no measurable effect on the cells until the concentrations reached greater than 200 µg/ml.

• But more 200 µg/ml doses has been found that nanostructured TiO2 particles could generate lung tumor and pulmonary fibrosis in rats.

• Fig 1. (A) to (C) images shows the morphology of mouse C18-4 spermatogonial stem cells by phase contrast microscopy after incubation with different types of nanoparticles for 48 h. Fig. A is a control specimen, Fig. B silver nanoparticles (15 nm Ag, 10 µg/ml), some cells retain an intact plasma membrane (arrows), indicating apoptosis. For fig C with Aluminum nanoparticles (30 nm Al, 10 µg/ml), the cytoplasm is clearly observed without apoptosis and necrosis.

• Fullerenes are a very important class of carbonbased nanostructured materials. The most common is a buckminsterfullerene (buckyballs), C60.

• C60 itself shows limited solubility in organic solvents but its solubility has been increased by chemical modification and functionalization, therefore, derivatized fullerenes have opened an avenue in the field of biological sciences including possible use in the pharmaceuticall industry.

• For example, C60-containing bilayer lipid membranes may be useful in a biosensor.

• In toxicity behavior, Yamago et al. stated when used a radiolabeled fullerene with C14 and found fast migration, with liver as the major target organ. It has been reported that fullerene derivatives could even pass through the blood–brain barrier/

• C60 having the least degree of derivatization was more toxic to cells. also shows that the toxicity of C60 based materials depends upon the degree of surface functionalization.

Table 1: Cytotoxicity of fullerene-based nanostructured materials.

• CNTs can be prepared into single-walled (SW)-, double-walled (DW)-, few-walled (FW), and multi-walled (MW) nanotubes.

• Carbon nanotubes (CNTs) are among the strongest and stiffest known materials.

• Single-w alled carbon nanotubes (SWCNTs) show potential for applications in sensors, drug delivery systems, pharmaceutics, electronics, photonics, display devices, reinforced composites, etc.

• The biocompatibility and toxicity of carbon nanotubes has been studied in experimental animals and humans.

• Liopo et al. stated that single-walled carbon nanotubes (SWCNTs) can support neuronal attachment and growth by chemical modifications.

• For the toxicity, Sharma et al. examined the toxicity of SWCNTs in rat lung epithelial cells. Lung epithelial cells (LE cells) were cultured with or without SWCNTs and reactive oxygen species (ROS) were measured by change in fluorescence.

• Exposure to SWCNTs caused oxidative stress in LE cells and showed loss of antioxidants.

• When, multiwall carbon nano-onions (MWCNOs) and multi-walled carbon nanotubes (MWCNTs) on human skin. Shows that’s, exposure increased apoptosis/necrosis effect.

• Fig. 7. Biodistribution histogram of 125I-SWNTols (352×106 cpm/ml, µ15 g/ml) in mice at eight different time intervals.

• Quantum dots have been used as a fluorescent labeling agents for both in vitro and in vivo studies for stem cell labeling, medical imaging , sensors, light-emittingdiodes, in vivo imaging,199 200 biological sensing, and multiplexing gene analysis.

• Recently, cytotoxicity of quantum dots (QDs) and deleterious effects of the labeling procedure on human mesenchymal stem cells has been reported.

• The cadmium-based quantum dots (QDs) showed cytotoxic effects.• The CdTe quantum dots induce cell death by involving both Cd2+

and reactive oxygen species (ROS) accompanied by lysosomal enlargement and intracellular redistribution

• Mainly released-diesel exhaust and petroleum fueled vehicle.

• Carcinogenic-radiation that is an agent directly involved in causing cancer

• Consist 36-44% of the total concentration.

Cytotoxicity• Cytotoxicity is the quality of being toxic to cell.

Examples of toxic agents are a chemical substance, an immune cells or some types of venom.

1. Apoptosis-(multicellular organism- include cell shrinkage, nuclear fragmentation, and chromosomal DNA fragmentation.)

2. Necrosis-(external to the cell or tissue, such as infection, toxins, or trauma that can lead to fatal.)

3. ROS generation-(Reactive oxygen species-oxidative stress, ionizing radiation.)

4. Plasma membrane damage.5. Cellular senescence-(normal diploid cells lose the

ability to divide, DNA double strand breaks due to toxins.)

APPROACHES FOR INCREASINGAPPROACHES FOR INCREASINGBIOCOMPATIBILITY AND BIOCOMPATIBILITY AND REDUCINGREDUCINGNANOTOXICITY OF NANOTOXICITY OF NANOSTRUCTUREDNANOSTRUCTUREDMATERIALSMATERIALS

• Nanotoxicology is the study of the toxicity of nanomaterials. Because of quantum size effects and large surface area to volume ratio, nanomaterials have unique properties compared with their larger counterparts.

• Nanotoxicology is a branch of bionanoscience which deals with the study and application of toxicity of nanomaterials.

• Toxic effects of nanostructured materials could be reduced by using different chemical approaches.

• Surface treatment and functionalization of nanomaterials could help in reducing toxic effects on human health.

Cytotoxicity

• Cytotoxicity of quantum dots depends on physicochemical and environmental factors.

• The cytotoxicity of nanomaterials depends upon their surface chemistry and surface characteristics

• Cytotoxicity is studied in vitro, which may not accurately indicate the comparative toxicity in vivo.

• Nanoparticles may have adverse effects on biological systems.

• In vitro: is a studies in experimental biology on an organism that isolated from their component which will done on the out side, (test tube experiment).

• Can be focus on the cell of the organism, so the result will be more accurately.

• But, in “in vitro” technique there is a few thing that must be alert such as the result, because sometimes the result will not be same with the real situation.

• In vivo: is a biological studies on a living things either partial or dead organism.

• As example, nowadays there is a in vitro research on HIV curing. Which still cannot work on the living organism. So in vivo still need to be done.

Increases in environmental exposure in air, water or soil.

Like other pollutants, they may pass from organism to organism.

Harmful effects on invertebrates and fish, including effects on behaviour, reproduction and development.

The main focus is on micro-organisms and invertebrates and studies on fish. The hazardous effects include:

Behaviour Growth and development Inflammatory responses Cytotoxic effects.

How to work safely with nanomaterials?

Based on particle physics and studies of fine atmospheric pollutants, the nanoparticle size range is the range of minimum settling. This means that once released into air, nanoparticles will remain airborne for considerable periods of time. Nanoparticles can be inhaled and will be collected in all regions of the respiratory tract; about 35% will deposit in the deep region of the lungs.

Because they are so small, nanoparticles follow airstreams more easily than larger particles, so they will be easily collected and retained in standard ventilated enclosures such as fume hoods. In addition, nanoparticles are readily collected by HEPA filters. Respirators with HEPA filters will be adequate protection for nanoparticles in case of spills of large amounts of material.

Because they are so small, nanoparticles follow airstreams more easily than larger particles, so they will be easily collected and retained in standard ventilated enclosures such as fume hoods. In addition, nanoparticles are readily collected by HEPA filters. Respirators with HEPA filters will be adequate protection for nanoparticles in case of spills of large amounts of material.

•Working safely with nanomaterials involves following standard (MSDS) - preventing inhalation, skin contact, and ingestion.

•Many nanomaterials are synthesized in enclosed reactors or glove boxes.

•The enclosures are under vacuum or exhaust ventilation, which prevent exposure during the actual synthesis.

•Inhalation exposure can occur during additional processing of materials removed from reactors, this processing should be done in fume hoods.

•In addition, maintenance on reactor parts that may release residual particles in the air should be done in fume hoods.

•Another process, the synthesis of particles using sol-gel chemistry, should be carried out in ventilated fume hoods or glove boxes.

•Working safely with nanomaterials involves following standard (MSDS) - preventing inhalation, skin contact, and ingestion.

•Many nanomaterials are synthesized in enclosed reactors or glove boxes.

•The enclosures are under vacuum or exhaust ventilation, which prevent exposure during the actual synthesis.

•Inhalation exposure can occur during additional processing of materials removed from reactors, this processing should be done in fume hoods.

•In addition, maintenance on reactor parts that may release residual particles in the air should be done in fume hoods.

•Another process, the synthesis of particles using sol-gel chemistry, should be carried out in ventilated fume hoods or glove boxes.