Nanotechnology, nano dust and health effects

By Dr. Hemantha WICKRAMATILLAKE

Director General, National Institute of Occupational Safety and Health, Ministry of Labour Relations

Scientists are experimenting with substances at the nanoscale

Nanotechnology, shortened to “nanotech”, is the study of the control of matter on an atomic and molecular scale. Generally, nanotechnology deals with structures of the size 100 nanometres or smaller in at least one dimension, and involves developing materials or devices within that size. Nanotechnology is very diverse, ranging from extensions of conventional device physics to completely new approaches based upon molecular self-assembly, from developing new materials with dimensions on the nanoscale to investigating whether matter can be controlled at nanoscale. A nanoparticle is a particle with lengths in 2 or 3 dimensions between 1 to 100 nm that may or may not have size related intensive properties. Nanomaterials are generally in the 1-100 nm range and can be composed of many different base materials (carbon, silicon, and metals such as gold, cadmium, and selenium).

Nanomaterials also have different shapes: referred to by terms such as nanotubes, nanowires, crystalline structures such as quantum dots, and fullerenes. Nanomaterials often exhibit very different properties from their respective bulk materials: greater strength, conductivity, and fluorescence, among other properties. For many types of nanoparticles, 50-100% of the atoms may be on the surface, resulting in greater reactivity than bulk materials. In order to understand the unusual world of nanotechnology, we need to get an idea of the units of measure involved. A centimetre is one-hundredth of a metre, a millimetre is one-thousandth of a metre, and a micrometre is one-millionth of a metre, but all of these are still huge compared to the nanoscale. A nanometre (nm) is one-billionth of a metre, smaller than the wavelength of visible light and a hundred-thousandth the width of a human hair. As small as a nanometre is, it’s still large compared to the atomic scale. An atom has a diameter of about 0.1 nm. Atoms are the building blocks for all matter in our universe. On the nanoscale, we can potentially put these atoms together to make almost anything. Experts sometimes disagree about what constitutes the nanoscale, but in general, one can think of nanotechnology dealing with anything measuring between 1 and 100 nm. Larger than that is the microscale, and smaller than that is the atomic scale. Particles in the nanometre size range do occur both in nature (e.g. volcano eruptions) and as an incidental byproduct of existing industrial processes (e.g. welding, smelting etc.). One concern about small particles that are less than 10 (microns) is that they are respirable and reach the alveolar spaces of the lungs.

The current nanotechnology revolution differs from past industrial processes because nanomaterials are being engineered and fabricated from the bottom up, rather than occurring as a byproduct of other activities. The nanomaterials being engineered have different and unexpected properties compared to those of the parent compounds. Since their properties are different when they are small, it is expected that they will have different effects on the body and will need to be evaluated separately from the parent compounds for toxicity. Currently nanomaterials are being introduced into the commercial market. Some nanmoaterials are used as catalyst supports in catalytic converters; nanosized titanium dioxide particles are used as a component of sunscreens; carbon nanotubes have been used to strengthen tennis rackets; components in silicon chips are reaching the 45 to 65 nm range. Research and industrial labs are working at the intersection of engineering and biology to extend uses to medicine as well as all areas of engineering. The impact is expected to revolutionize these areas. Government agencies in the US and Europe are beginning to fund toxicology research to understand the hazards of these materials before they become widely available.

Quantum mechanics

One of the exciting and challenging aspects of the nanoscale is the role that quantum mechanics plays in it. The rules of quantum mechanics are very different from classical physics, which means that the behaviour of substances at the nanoscale can sometimes contradict common sense by behaving erratically. Usually one cannot walk up to a wall and immediately teleport (transport by dematerializing at one point and assembling at another) to the other side of it, but at the nanoscale an electron can; it is called electron tunnelling. Substances that are insulators, meaning they can’t carry an electric charge in bulk form, might become semiconductors when reduced to the nanoscale. Melting points can change due to an increase in surface area.

Much of nanoscience requires that we forget what we know and start learning all over again. So what does this all mean? Right now, it means that scientists are experimenting with substances at the nanoscale to learn about their properties and how it might be able to take advantage of them in various applications. Engineers are trying to use nano-size wires to create smaller, more powerful microprocessors. Doctors are searching for ways to use nanoparticles in medical applications. Still, there is a long way to go before nanotechnology dominates the technology and medical markets.

Currently, scientists find two nano-size structures of particular interest: nanowires and carbon nanotubes. Nanowires are wires with a very small diameter, sometimes as small as 1 nanometre. Scientists could build tiny transistors for computer chips and other electronic devices. In the recent past, carbon nanotubes have overshadowed nanowires. A carbon nanotube is a nano-size cylinder of carbon atoms. With the right arrangement of atoms, one can create a carbon nanotube that’s hundreds of times stronger than steel, but six times lighter. Engineers plan to make building material out of carbon nanotubes, particularly for items like cars and airplanes. Carbon nanotubes can also be effective semi-conductors with the right arrangement of atoms. Some products already manufactured are sunscreens containing nanoparticles of zinc oxide or titanium oxide, self-cleaning glass which uses nanoparticles to make the glass photocatalytic and hydrophilic, clothing where fabrics are coated with a thin layer of zinc oxide nanoparticles, manufacturers can create clothes that give better protection from UV radiation, scratch-resistant coatings, antimicrobial bandages using nanoparticles of silver where silver ions block microbes’ cellular respiration, tennis rackets and swimming pool cleaners and disinfectants with nano-sized oil drops mixed with a bactericide.

New products

New products incorporating nanotechnology are coming out everyday.

Any toxic effects of nanomaterials will be very specific to the type of base material, size, ligands, and coatings. One of the earliest observations was that nanomaterials, also called ultrafine particles (100 nm), showed greater toxicity than fine particulates (2.5 um) of the same material on a mass basis. This has been observed with different types of nanomaterials, including titanium dioxide, aluminum trioxide, carbon black, cobalt, and nickel. For example, Oberdorster (1994) found that 21 nm titanium dioxide particles produced 43 fold more inflammation (as measured by the influx of polymorphonuclear leucocytes, a type of white blood cell, into the lung) than 250 nm particles based on the same mass instilled into animal lungs. Though multiple studies have shown that nano-sized particles may be more toxic than micro-sized particles, this is not always the case. Wang (2008) showed that nanoscale titanium dioxide when inhaled could travel to the brain by way of olfactory neurons.

Once in the brain, it caused oxidative stress and neuronal degeneration in several areas, including the hippocampus which is involved with short-term memory. Nanoscale titanium dioxide joins several other types of nanomaterials (manganese oxide, nano carbon, and some viruses) that can enter the brain directly by means of the olfactory pathway from the nose. Researchers led by Ken Donaldson of the University of Edinburgh Centre for Inflammation Research, UK, found that in mice, long, straight, multi-walled carbon nanotubes can cause the same kind of damage (cancer) as that inflicted by asbestos fibres when they are injected into the lung’s outer lining, called the mesothelium.

Nanoscale titanium dioxide has shown very different properties from the micron scale material in tests of lung toxicity. Fourteen to 40 nm titanium dioxide produced lung cancer in rats at doses of 10 mg/m3; micron sized dust produced cancer only at very high doses (250 mg/m3). Based on these results the National Institute of Occupational Safety and Health (NIOSH) issued a recommended safe occupational exposure limit of 0.1 mg/m3 for nanoscale material and 1.5 mg/m3 for micron size material.

The International Agency for Research on Cancer (IARC) has also determined that titanium dioxide is a category 2B carcinogen: possibly carcinogenic to humans. There is currently no consensus about the ability of nanoparticles to penetrate through the skin. Particles in the micrometre range are generally thought to be unable to penetrate through the skin. The outer skin consists of a 10 m thick, tough layer of dead keratinized cells (stratum corneum) that is difficult to pass for particles, ionic compounds, and water soluble compounds. Micronized titanium dioxide (40 nm) is currently being used in sunscreens and cosmetics as sun protection. The nano particles are transparent and do not give the cosmetics the white, chalky appearance that coarser preparations did. Carbon nanotubes (CNT) can have either single or multiple layers of carbon atoms arranged in a cylinder. The dimensions of typical single wall carbon nanotubes (SWCNT) are about 1-2 nm in diameter by 0.1 um in length.

Multiple wall carbon nanotubes (MWCNT) are 20 nm in diameter and 1 mm long. CNT may behave like fibres in the lung. They have properties very different from bulk carbon or graphite. They have great tensile strength and are potentially the strongest, smallest fibres known. CNT have been tested in short term animal tests of pulmonary toxicity and the results suggest the potential for lung toxicity though there are questions about the nature of the toxicity observed and the doses used. Fullerenes are another category of carbon based nanoparticles.

The most common type has a molecular structure of C60 which take the shape of a ball shaped cage of carbon particles arranged in pentagons and hexagons. Fullerenes have many potential medical applications as well as applications in industrial coatings and fuel cells, so a number of preliminary toxicology studies have been done with them.

In cell culture, different types of fullerenes produced cell death at concentrations of 1 to 15 ppm in different mammalian cells when activated by light (as discussed in Colvin, 2003). Sayes (2004) found that toxicity could be eliminated when carboxyl groups were substituted on the fullerene surface to increase water solubility.

Nanoparticles (0.1 um) are generally similar in size to proteins in the body. They are considerably smaller than many cells in the body. Human alveolar macrophages are 24 nm in diameter and red blood cells are 7-8 nm in diameter. Cells growing in tissue culture will pick up most nanoparticles. Thus, the ability to be taken up by cells is being used to develop nanosized drug delivery systems and does not inherently indicate toxicity. Gold nanoparticles are being investigated as transfection agents, DNA-binding agents, protein inhibitors and other biomedical applications.

Once in the body, some types of nanoparticles may have the ability to translocate and be distributed to other organs, including the central nervous system.

Silver, albumin, and carbon nanoparticles all showed systemic availability after inhalation exposure. Quantum dots (QD) are nanocrystals containing 1000 to 100,000 atoms and exhibiting unusual quantum effects such as prolonged fluorescence. They are being investigated for use in immunostaining as alternatives to fluorescent dyes.

The most commonly used material for the core crystal is cadmium-selenium, which exhibits bright fluorescence and high photostability. Both bulk cadmium and selenium are toxic to cells. One of the primary sites of cadmium toxicity in vivo is the liver.

Working safely with nanomaterials

How to work safely with Nanomaterials. The preliminary conclusions to be drawn from the toxicology studies to date are that some types of nanomaterials can be toxic, if they are not bound up in a substrate and they are available to the body.

Multiple government organizations are working to fund and assemble toxicology information on these materials.

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 procedures that would be followed for any particulate material with known or uncertain toxicity: preventing inhalation, dermal, and ingestion exposure. Concerning skin contact, Maynard (Authorm) former superior officer), found clumps of nanoropes on the gloves of workers removing the synthesized materials from the reactors. Since the ability of nanoparticles to penetrate the skin is uncertain at this point, chemical resistant gloves should be worn when handling particulate and solutions containing particles. One potential safety concern with nanoparticles is fires and explosions if large quantities of dust are generated during reactions or production. This is expected to become more of a concern when reactions are scaled up to pilot plant or production levels.

As nanotechnology emerges and evolves, potential environmental applications and human health and environmental implications are under consideration by the EPA and local regulators.

There are currently no guidelines from the EPA specifically addressing disposal of waste nanomaterials.

It seems that regulation at some level is inevitable. The following waste management guidance applies to nanomaterial-bearing waste streams consisting of:

Pure nanomaterials (e.g., carbon nanotubes), items contaminated with nanomaterials (e.g., wipes/PPE), liquid suspensions containing nanomaterials, solid matrixes with nanomaterials that are friable or have a nanostructure loosely attached to the surface such that they can reasonably be expected to break free or leach out when in contact with air or water, or when subjected to reasonably foreseeable mechanical forces.

(The writer was formerly a Senior Environmental Health Scientist with the MRC, UK and an Environmental Health Specialist with the World Health Organisation, Europe Office)