The succesful application of...

 

manufactured nanomaterials in nano-enabled products may lead to emissions in the environment, with an incomplete hazard and risk assessment. The ‘invasion’ of new manufactured nanomaterials and nano-enabled products into nearly every aspect of modern life has raised concerns and increased calls for the application of the precautionary principle to safeguard the health of humans and the environment.

 

When released in the workplace or the environment nanomaterials may be dangerous. The skin, gastrointestinal tract, nasal olfactory structures and the eyes are the major portals through which nanoparticles can enter the body as a result of occupational or environmental exposures.[30]

After exposure, nanoparticles can travel through the blood and lymph circulating system reaching distant organs including the cardiovascular system and brain.[31],[32]

 

Of primary concern in occupational settings are inhalation of nanoparticles and skin exposure.

So far, healthy skin has shown little penetration potential, however, there are several studies that illustrate that the condition of the skin (barrier integrity, anatomic structure, skin diseases, etc.) may influence uptake.[33] Inhalation is the most relevant exposure route of manufactured nanomaterials and the lungs and pleura are the primary targets for adverse effects. It is possible for the inhaled nanoparticles to penetrate the lungs and deposit themselves in the respiratory system. It is believed that inhaled nanoparticles have reduced clearance from lungs relative to larger particles and can have increased transfer into the blood stream.[34],[35]  Inhaled ambient ultra-fine particles can be found in the heart, bone marrow, liver, kidney and even the central nervous system.[36]

 

When nanomaterials have entered the human body they can take part in reactions within cells, with the potential to exhibit adverse health effects. The primary toxicity concern of nanoparticles is the damage that is caused by free radical generation, which can provoke intense oxidative stress, inflammation and cell damage in the body.[37],[38] Oxidative stress is defined as an imbalance between oxidants and antioxidants inside cells, in lung lining fluid or tissue fluid.

Preliminary data indicates that acute toxicity and systemic effects on different organ systems, including the immune, inflammatory and cardiovascular systems may occur.[39]

Furthermore, genotoxicity and possible carcinogenesis and teratogenicity may occur, but no data on these latter endpoints is available yet.[40]

 

The form of nanomaterials is an important issue in hazard and risk assessment. Carbon nanotubes (CNT) were shown to be able to induce asbestos-like alterations in the mesothelium of the mouse peritoneal cavity[41] and increase the likelihood of mesotheliomas in sensitive mouse strains.[42] Long CNTs may give an acute inflammation leading to progressive fibrosis of the pleura, while this is not the case for short CNTs.[43]

 

In conclusion, much is still unknown, but it is clear that nanomaterials are likely to interfere with cellular organization and affect biological functions in ways that cannot be deduced from previous experience with macro- or micro particles.[44] Therefore, there is an urgent need for improved characterization and reliable toxicity screening tools (all still very limited) to elucidate health and environmental impacts, as it has been shown that the ones available (targeted to bulk chemicals and substances) might not be suitable for the assessment of nano-risks. Relevant in this respect is to further operationalize the paradigm change in risk assessment from a mass-based approach towards a particles’ number based approach.

Potential effects of inhaled nanoparticles

[30] Borm PJA, Robbins D, Haubold S, Kuhlbusch T, Fissan H, Donaldson K, Schins R, Stone V, KreylingW, Lademann J, Krutmann J, Warheit D, Oberdorster E. The potential risks of nanomaterials: a review carried out for ECETOC. Particle and Fibre Toxicology, 3:11, 2006.

[31] Nel A, Xia T, Mädler L, Li N. Toxic Potential of Materials at the Nanolevel. Science, 311:622-627, 2006.

[32] Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A. Rapid translocation of nanoparticles from the lung airspaces to the body. Nature Biotechnology, 28: 1300–1304, 2010.

[33] Monteiro-Riviere NA, Filon FL (2012), Skin, In: Adverse effects of engineered nanomaterials – Exposure, Toxicology, and Impact on Human Health, Eds. Fadeel B, Pietroiusti A, Shvedova AA. Academic Press, 2012.

[34] Geiser M, Casaulta M, Kupferschmid B, et al. The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles. Am J Respir Cell Mol Biol, 38 (3): 371-376, 2008.

[35] Oberdörster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, et al. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol, 16: 437-45, 2004.

[36] Kleinman MT, Araujo JA, Nel A, Sioutas C, Campbell A, Cong PQ, Li H, Bondy SC. Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways. Toxicology Letters, 178: 127–130, 2008.

[37] Li N, Xia T, Nel AE. The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radical Biology and Medicine, 44(9):1689-1699, 2008.

[38] Shvedova AA, Kagan VE, Fadeel B. Close Encounters of the Small Kind: Adverse Effects of Man-Made Materials Interfacing with the Nano-Cosmos of Biological Systems. Annu Rev Pharmacol Toxicol, 50:63–88, .2010.

[39] Park EJ, Yi J, Chung KH, Ryu DY, Choi J, Park K. Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. Toxicology Letters, 2008, 180 (3): 222-229.

[40] Bouwmeester H, Dekkers S, Noordam MY, Hagens WI, Bulder AS, Heer C, Voorde SECG, Wijnhoven SWP, Marvin HJP,. Sips AJAM. Review of health safety aspects of nanotechnologies in food production. Regulatory Toxicology and Pharmacology, 2009, 53 (1): 52-62.

[41] Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH, Seaton A, Stone V, Brown S, MacNee W, Donaldson K. Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study.Nat. Nanotechnol. 3, 423–428, 2008.

[42] Takagi A, Hirose A, Nishimura T, Fukumori N, Ogata A, Ohashi N, Kitajima S, Kanno J. Induction of mesothelioma in p53+/− mouse by intraperitoneal application of multi-wall carbon nanotube. J. Toxicol. Sci. 33, 105–116, 2008.

[43] Murphy FA, Poland CA, Duffin R, Al-Jamal KT, Ali-Boucetta H, Nunes A, Byrne F, Prina-Mello A, Volkov Y, Li S, Mather SJ, Bianco A, Prato M, MacNee W, Wallace WA, Kostarelos K, Donaldson K.Length-Dependent Retention of Carbon Nanotubes in the Pleural Space of Mice Initiates Sustained Inflammation and Progressive Fibrosis on the Parietal Pleura. American Journal of Pathology, 178(6):2587-2600, 2011.

[44] Kagan VE, Shi J, Feng W, Shvedova AA, Fadeel B. Fantastic voyage and opportunities of engineered nanomaterials: What are the potential risks of occupational exposures? Journal of Occupational and Environmental Medicine, 52(9):943-946, 2010.