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SCENIHR (2009)

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4. What are the potential health effects of nanomaterials?

4.1 How do nanoparticles interact with proteins?

Living organisms contain many molecules which interact with nanoparticles. Most often, nanomaterials will become coated with protein molecules. This “corona” of proteins is a shifting population of different molecules. Some influence the body’s immune defence system. Others may help nanoparticles penetrate the tissuea.

There is evidence from laboratory studies that some nanoparticles can promote clumping of protein molecules, which speeds up formation of self-assembling fibrils of a kind linked with a number of medical conditions. In amyloid disease, these produce plaques which the cell has difficulty disposing of.

Experiments in vitro in the laboratory have shown that several different kinds of nanoparticles can increase formation of a nucleus for protein fibrils from the purified human blood protein beta-2 macroglobulin. It is not known if this can also happen in the organism.

There are also indications that nanoparticles can be transported from the upper lining of the nose into the brain. This is a concern because of the role of amyloid plaques in some brain diseases. More research is needed here.


4.2 How can nanomaterials be transported in the body?

Nanoparticles enter the body by crossing one of its outer layers, either the skin or the lining of the lungs or the intestine. How well they transfer from outside to inside will depend on the particular physical and chemical properties of the particle.

Once inside, the particles will move with the circulation into all the organs and tissues of the body. Nanoparticles injected into the bloodstream of laboratory animals are found in organs including the liver, spleen, heart and brain. Direct cell-to- cell transfer is unlikely as the junctions between cells have pores which are even smaller than nanoparticles (a nanometre or less). However, cell membranes admit some particles, and have transport mechanisms for others, depending on the cell type.

Research on nanoparticle transport in the body has often used colloidal gold nanoparticles, which are easy to detect and do not harm cells - they are potential carriers of drugs, imaging molecules, and perhaps genes and cancer therapy agents. There is also work with titanium dioxide, the common white pigment.

Experiments on rats show that the distribution of gold nanoparticles depends on their size, with the smallest particles - 10 nanometres - spreading to most organs, while those 100 nanometres or more were mainly held in the spleen and liver. The particles stay in the body longer if they are made of water-loving material, and carry a positive electric charge. For some particles, either the particles themselves or a chemical component of the particle can be detected in all organs tested, including the brain and the reproductive system. There is some evidence that very small nanoparticles can transfer from a pregnant rat to the fetus.

The concentration of nanoparticles in the spleen and liver aids their elimination, as both these organs are well supplied with cells, phagocytes, which ingest foreign matter.

Results from experiments in which gold or titanium dioxide particles are given by mouth or inhaled are broadly similar to those involving injection into the bloodstream, although fewer such studies involve the smallest particles. Smaller particles are more widely distributed, while the largest are more likely to remain in the digestive system, or the lungs, and so be eliminated more rapidly.

If humans inhale carbon nanoparticles, most remain in the lungs, with less than one per cent crossing into the blood circulation.

Nanoparticles which are not absorbed by the gut or the lungs eventually leave the body in the faeces - either directly or after they are moved up from the lungs by normal clearance of mucus and then swallowed. Even insoluble nanoparticles which reach the finely branched alveoli in the lungs can be removed by macrophage cells engulfing them and carrying them out to the mucus, but only 20 to 30 per cent of them are cleared in this way. Nanoparticles in the blood can also be filtered out by the kidneys and excreted in urine. Long-term results are scanty, but it is wise to assume that unexcreted nanoparticles will accumulate in organs they can reach if exposure continues over long periods.


4.3 What are the potential effects of carbon nanotubes?

Concern about possible health effects of carbon nanotubes centres on their partial resemblance to the type of long, thin asbestos microfibres which can cause the cancer mesothelioma. Carbon nanotubes are cylindrical molecular assemblies of pure carbon whose manufacture followed discovery of the new carbon structures known as fullerenes, and are usually a few nanometres across. They can be produced in many variations. There are results which indicate that the certain specifically prepared nanotubes - long and straight, and persistent - do produce the same effects on susceptible tissues as asbestos fibres. Any actual health risk would depend on whether they are ever inhaled.

However, most carbon nanotubes are tangles of tubes, more like a ball of string, rather than straight fibres. These can be harmful to the lungs, and cause inflammation, tissue alterations and vulnerability to infection.

The experimental results suggest that any manufacture of nanotubes should guard against lung exposure. It is likely that any other nanoparticles which are also long and thin, and persistent (are not metabilised), nanowires or nanorods, would also pose a hazard if they were more than 20 micrometers long.


4.4 Can nanomaterials have genetic effects?

Outside agents can affect the genes inside a cell either directly or by causing inflammation. Nanoparticles might also act in either of these ways. There is some evidence that they can pass into compartments inside the cell, including the nucleus which houses the vast majority of the genes. That means that they can interact directly with DNA, or affect by producing reactive oxygen species (often known as free radicals) in the vicinity of the genetic material. Acquiring a protein coat may help nanoparticles penetrate the tissues. The coating can help the particles cross the boundary membrane around a cell, or the nuclear membrane around the cell’s DNA. The latter effect has been demonstrated with gold nanoparticles bound to a specific nuclear protein.

Harmful genetic effects have been reported for some manufactured nanomaterials tested on cells in culture, mainly linked with production of free radicals. The damage may include DNA damage, chromosomal alterations, or gene mutations, detected by different assays. A few nanomaterials have registered positive in such tests for all three types of damage.

Some nanomaterials have been intensively studied for genetic effects, and results are frequently inconsistent - depending on the kind of test used, the cell lines and the precise conditions for delivery of the nanomaterials to the culture. This makes it harder to interpret their relevance to nanomaterials in use.

There are in theory additional potential harmful effects from nanomaterials, including mechanical interference with chromosome movements during cell division and other sources of damage to DNA such as metal release from nanoparticles.


4.5 Do nanoparticles have effects on the heart and blood vessels?

Earlier studies of air pollution, which may involve microparticulates approaching the nano scale, suggest that manufactured nanoparticles could affect the cardiovascular system, the heart and blood vessels, although the exact mechanisms are not well understood. However, there is no clear evidence yet that this risk arises with manufactured nanoparticles. More information if needed to understand this possibility better.

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