B) Evidence of probable harm to health associated with exposure to nanoparticles

B) Evidence of probable harm to health associated with exposure to nanoparticles

The properties of matter change at the nano-scale, as the laws of classical physics give way to quantum effects. The physical properties of nano-sized particles can therefore be quite different from those of larger particles of the same substance. Altered properties can include colour, solubility, material strength, electrical conductivity and magnetic behaviour. Nano-sized particles also have a greater surface area relative to mass. This makes them much more chemically reactive (1).

The altered properties of nano-sized particles have created new possibilities for profitable products and applications. These altered properties also raise significant health and environmental risks that remain poorly studied, poorly understood and wholly unregulated. However the little peer-reviewed toxicological research that has been published regarding the health and environmental impacts of nanoparticle exposure is extremely concerning.

One risk that is clearly understood is the enhanced toxicity of nano-scale material (2). Many studies have found a clear inverse relationship between toxicity of insoluble materials and particle size, irrespective of parent material (3) .

The global reinsurance giant Swiss Re warns that at the nano-scale even normally harmless substances may become hazardous (4). This renders toxicity tests of larger quantities of a substance irrelevant to determining the safety of nano-sized relatives - a fact that is yet to be reflected in the regulatory system.

Unlike larger microparticles, nanoparticles are highly mobile and readily enter the blood stream following inhalation or ingestion. It also appears likely that nanoparticles can penetrate human skin and gain access to the blood stream (5).

Inhaled nanoparticles penetrate the protective mucus lining of human lungs and have high rates of deposition in the deeper lungs. Scavenger cells usually intercept foreign bodies and larger sized particles that make it past the mucus lung lining and into the deeper lung (6). However scientific studies have shown that these cells have difficulty recognising nano-scale particles, are readily overloaded, and their action is impaired (7).

Irrespective of their chemical composition, nanoparticles are potent inducers of inflammatory lung injury (8). The UK Health and Safety Executive note that persistent lung inflammation as a result of exposure to nanoparticles (as with other toxic dust) is likely to lead to diseases such as fibrosis and cancer (9). Organisations as diverse as The Workers' Health International News' (Hazards Magazine) (10) and Swiss Re global reinsurers (11) are making the comparison between exposure to nanoparticles and asbestos (see below).

Additional to causing direct lung damage, laboratory studies have repeatedly shown that nanoparticles cross from the deeper lungs to the blood stream. Once in the blood stream, nanoparticles are transported around the body and are absorbed by organs and (12,13) tissues including the brain, heart, liver, bone marrow, ovaries and muscles. Inhaled nanoparticles can travel directly to the brain along olfactory nerve cells (14). This is of particular concern given recent findings that nanoparticles cause brain damage to fish (15) and dogs (16).

Ingested nanoparticles can be absorbed into the lymphatic system, and from there the blood stream, by intestinal tissue nodules known as "Peyer's plaques" (17). As a general rule, the smaller the particle the greater is its absorption.

It has been shown that microparticles can penetrate human skin (18). The UK Health and Safety Executive (19) note that skin penetration by nanoparticles is comparatively even more likely. Scientists have suggested that nanoparticles may penetrate into hair follicles and then enter the deeper skin, from where they could access the blood stream. Several pharmaceutical companies are believed to be developing nanoparticles for dermal penetration as a drug delivery route, based on their ability to gain access to the blood stream.

The duration of deposits of nanoparticles in vital organs is unknown, although there is some evidence to suggest they may accumulate in organs such as the liver (20). The extent of damage they may do and what dose may cause a harmful effect remains unknown. However scientists have shown that even low levels of nanoparticles are toxic to human liver cells (21). Other diseases of the liver suggest that the accumulation of even harmless foreign matter may also impair its function and result in harm.

Neuro-degenerative diseases such as Alzheimer's or Parkinson's are thought to be caused by a disruption of the iron concentration in the brain. However, iron oxide nanoparticles are already being used in a number of applications, for example magnetic resonance scans (22).

1 The Royal Society and The Royal Academy of Engineering, UK. 2004. Nanoscience and nanotechnologies. Available at http://www.royalsoc.ac.uk/

2 The Royal Society and The Royal Academy of Engineering, UK. 2004. Nanoscience and nanotechnologies. Available at http://www.royalsoc.ac.uk/

3 Institute of Occupational Medicine for the Health and Safety Executive. 2004. Nanoparticles: An occupational hygiene review. Available at http://www.hse.gov.uk

4 Swiss Re. 2004. Nanotechnology: Small matter, many unknowns. Available at http://www.swissre.com

5 Institute of Occupational Medicine for the Health and Safety Executive. 2004. Nanoparticles: An occupational hygiene review.Available at http://www.hse.gov.uk

6 Wichmann HE and Peters A. 2000. "Epidemiological evidence of the effects of ultrafine particle exposure". Philos. Trans. R. Soc. Lond. A 358:2751-2769.

7 Wichmann HE and Peters A. 2000. "Epidemiological evidence of the effects of ultrafine particle exposure". Philos. Trans. R. Soc. Lond. A 358:2751-2769.

8 US National Institute of Environmental Health Services.2003. Factsheet: Nanotechnology Safety Assessment: National Toxicology Program. Available at http://www.niehs.nih.gov/oc/factsheets/nano.htm

9 Institute of Occupational Medicine for the Health and Safety Executive. 2004. Nanoparticles: An occupational hygiene review. Available at http://www.hse.gov.uk

10 Workers Health International News. 2004. "Nanotech safety". Hazards Magazine. Issue 87 July-September. Available at http://www.hazards.org

11 Swiss Re. 2004. Nanotechnology: Small matter, many unknowns. Available at http://www.swissre.com

12 Oberdörster G, Sharp Z, Atuderoi V, Elder A, Gelein, R, Lunts A, Kreyling W, Cox C. 2002. "Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats." Journal of Toxicology and Environmental Health. Part A, 65:1531-1543

13 Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdörster G, Ziesenis A. 2002. "Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low." Journal of Toxicology and Environmental Health. Part A, 65:1513-1530.

14 Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. 2004. "Translocation of inhaled ultrafine particles to the brain". Inhal Toxicol. 16(6-7):437-45.

15 Oberdörster E. 2004. Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass. Environ. Health Perspect., 112, 1058-1062.

16 Cited in UK Trades Union Congress. 2005. Nanotechnology Factsheet. Available at http://www.tuc.org.uk/h_and_s/tuc-8350f0.cfm

17 Swiss Re. 2004. Nanotechnology: Small matter, many unknowns. Available at http://www.swissre.com

18 Tinkle SS, Antonini JM, Roberts JR, Salmen R, DePree K, Adkins EJ. 2003. "Skin as a route of exposure and sensitisation in chronic beryllium disease", Environmental Health Perspectives. 111:1202-1208. Available at http://ehp.niehs.nih.gov/members/2003/5999/5999.html

19 Institute of Occupational Medicine for the Health and Safety Executive. 2004. Nanoparticles: An occupational hygiene review. Available at http://www.hse.gov.uk

20 Oberdörster G, Sharp Z, Atuderoi V, Elder A, Gelein, R, Lunts A, Kreyling W, Cox C. 2002. "Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats." Journal of Toxicology and Environmental Health. Part A, 65:1531-1543

21 Sayes C M, Fortner JD, Guo W, Lyon D, Boyd AM, Ausman KD, Tao YJ, Sitharaman B, Wilson LJ, Hughes JB, West JL,Colvin VL. 2004. "The differential cytotoxicity of water-soluble fullerenes". Nanolett. 4, 1881-1887.

22 Swiss Re. 2004. Nanotechnology: Small matter, many unknowns. Available at http://www.swissre.com