Q: Are nanoparticles/nanotechnology dangerous for humans?

A: The overarching purpose of nanotechnology is to create better circumstances for humans and environment. If the nano industry can grow, it can help us to solve the energy crisis, save the environment, and diagnose and cure adverse diseases. Nanotechnology can be used for cheap and easy water purification, available and cheap energy, faster computers, long-lasting mobile phone batteries, implants, diagnose of diseases, better surgical tools, and targeted delivery of medicine. The things in nano technology that might pose a risk to us or to the environment are related to the fact that we need to make sure that we handle these new particles and materials in a safe way. The thing that makes nanoparticles so interesting for applications is that materials in nanosize have properties (optical, chemical, magnetic, biological, electrical, and mechanical) that are completely different from the properties of the same material in bulk. These new properties may cause a problem if nanoparticles are unintentionally released – very few of these particles exist in nature and we as humans have not been exposed to them throughout evolution. Therefore, we cannot be sure that our body have developed defense mechanisms to deal with them.  

Q: How can nanoparticles enter our body, and what happens if they do?

A: Nanowires, and all other kinds of nanomaterials, can potentially enter our body in three ways: through the skin, through the gastrointestinal tract, or through inhalation. Based on current knowledge, the most important exposure route for nanoparticles is inhalation. It is unlikely that nanoparticles would penetrate healthy skin, (still, it is a good idea to wear protective gloves e.g. nitrile gloves if you handle nanoparticles occupationally). To avoid exposure through the gastrointestinal tract, food and drinks should never be ingested in the same laboratory or room as nanoparticles are handled.
If inhaled, nanoparticles have a high probability of deposition in the lungs. How much is deposited depends on particle properties such as size, and physiological factors such as oral or nasal inhalation and exercise or rest.. Whilst impaction and interception are factors that are more dominant for micro-sized particles, nanosized particle depositions are more driven by diffusion (in particular at low air speed, such as in the alveoli) and surface charge. An important consideration in the deposition of particles in the respiratory system is the lung-lining fluid (a complex mixture of lipids and surfactant proteins) since any depositing material quickly becomes coated in these surfactant proteins and lipids. Such a coating gives the deposited particle its ‘biological identity’ [Lynch 2007, Treuel 2015]. This so-called protein corona, which is likely to play a role in the way particles interact with lung cells such as alveolar macrophages. If deposited in the deeper part of the lung, the alveoli tract, they are cleared either by the macrophages engulf particles that are deposited in the alveolar tract, and if they fail in doing this, the particles can be translocated from their primary organ of entry (the lung) to a secondary organ via the circulatory system.  In the tracheobronchial tract, particles are cleared by the mucociliary elevator, which transports particles up to the pharynx, after which they are swallowed and thereby enter the gastrointestinal tract. Among other parameters, the translocation rate and fraction to other organs depend on particle size, morphology, surface parameters such as composition, charge, and primary and secondary coatings with proteins, lipids and functional groups.
Inhaled nanoparticles can also translocate along sensory neuronal pathways to reach secondary organs and tissues such as the vascular endothelium, the heart and the brain.

Q: Are nanoparticles extra dangerous for kids?

A: A higher physical activity leads to a higher breathing frequency and thereby a larger number of inhaled particles per unit time. This in combination with that the lungs of children are under development and that children have less understanding for what potential dangers to avoid, makes children more susceptible than adults when it comes to all kinds of particle exposures.

Q: Is occupational exposure to nanoparticles a problem?

A: Occupational exposure of nanoparticles can occur in three ways: by inhalation, by ingestion, or by skin penetration. The most common, and thereby most important route is by inhalation. It is likely that exposure of nanoparticles involves certain risks. The toxicity of nanomaterials can vary from those that are non-toxic or slightly toxic to those that are highly toxic. Fiber-shaped nanoparticles are often considered especially toxic, and animal studies have shown that some are even carcinogenic. The precautionary principle should always be applied as long as the specific toxicity is not fully evaluated and as long as there are no nanospecific occupational exposure limits. This means that companies/industries that produce or handle nanomaterial should apply a high level of elimination and protection measures in the work environment to limit, control and minimize the airborne exposure of nanoparticles.
Nanomaterial can be ingested by unintentional hand-to-mouth contact. The risks of skin uptake are likely to be lower than inhalation; the skin, as long as it is not very dry or damaged, is ab effective barrier.
Several studies on workers exposed to carbon nanotubes have shown a significant increase of biomarkers of fibrosis. The organization for cancer research (IARC) of the World Health Organization (WHO) have classified one type of carbon nanotubes (Mitzui 7) as potentially carcinogenic in humans [IARC 111]. The National Institute for Occupational Safety and Health (NIOSH) has suggested an occupational exposure limit based on elementary carbon especially for carbon nanotubes: 0,001 mg/m3.
Even spherical nanoparticles, when in aggregates, are more toxic per unit mass than larger particles of the same material. This is due to that they, likely because of their larger surface area, induces more inflammation in the lungs. In addition, particles in nanosize are more likely to reach the periphery lung (the alveoli) than larger ones, and they have higher probability to become airborne during handling. The higher likeliness of becoming airborne is the cause of the suggested occupational exposure limit, by NIOSH, for nano titanium dioxide (0.3 mg/m3).

Q: Why are fibrer shaped nanoparticles more likely to be toxic than others?

A: The small diameter of a fiber makes it align itself to the airflow - this means it has a small aerodynamic diameter compared to its length, and that it thereby can reach the deeper (alveoli) parts of the lung. Once deposited in the alveoli, the fiber-shaped particle cannot, if longer than 4 µm be engulfed by a macrophage [Donaldson et al 2010]. This causes cytokine production, which initiates an inflammatory response that attracts immune cells, all of which can cause oxidative stress. The fiber, if biopersistent, will remain in the alveoli (causing accumulation with time) or will be translocated and end up in another organ. Hence, fiber-shaped particles are more toxic to the lung than spherical particles of the same aerodynamic diameter.

Q: How can you protect yourself from nanoparticles in the work environment?

A: For protection in work environments, the exposure shall be minimized by usage of elimination- and protective measures such as closed systems, encapsulation, fume hoods, LAF benches, process ventilation and local exhaust ventilation. Together with these measures, sometimes advanced personal protection equipment is needed (eg. Fan-assisted respirator with particle filter P3/FFP3, nitrile gloves, membrane material coveralls). To avoid contamination of other surfaces (eg. keyboards), gloves should be dispersed of directly after use. It is the responsibility of the employer to provide safe ways to handle nanomaterials at the workplace. This shall be done by examine the work environment to identify existing risks, evaluate them, and take the measures needed to eliminate, or minimize, them.  It is also the employer’s responsibility to provide relevant information and education and, if needed, relevant personal protection equipment and possibility for medical examinations
The precautionary principle should always be applied as long as the specific toxicity is not fully evaluated and as long as there are no nanospecific occupational exposure limits. This means that companies/industries that produce or handle nanomaterial should apply a high level of elimination and protection measures in the work environment to limit, control and minimize the airborne exposure of nanoparticles.
According to Swedish rules (16§ AFS 2014:43 Kemiska arbetsmiljörisker from Arbetsmiljöverket), protective measures should be prioritized according to the so called measure staircase (åtgärdstrappa, in Swedish). This dictates a stepwise approach by conduction one or more of the following measures in this given order: engineering protective measures, process ventilation, administrative measures, and personal protection equipment. Sometimes it can turn out to be necessary to use all of these in combination.

References

Lynch I, Cedervall T, Lundqvist M, Cabaleiro-Lago C, Linse S, Dawson KA (2007). The nanoparticle-protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century. Adv Colloid Interface Sci 134–135:167–174

Treuel L, Docter D, Maskos M, Stauber RH (2015) Protein corona – from molecular adsorption to physiological complexity. Beilstein J Nanotechnol 6:857–873

IARC Momographs Volume 111: https://monographs.iarc.fr/iarc-monographs-on-the-evaluation-of-carcino…

Donaldson K, Murphy FA, Duffin R et al. (2010) Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol; 7: 5.