Toxicity of nanomaterials

Degradability is an important factor in the assessment of the toxicity of nanomaterials [71]. Nondegradable nanomaterials may in fact accumulate in organs and/or intracellularly, where they would exert toxic effects. 

Nanoscale materials are known to have various shapes and structures such as spherical, needle-like, tubes, platelets, and so on. The effects of the shape on the toxicity of nanomaterials are unclear. The shape of nanomaterials may have effects on the kinetics of deposition and absorption to the body. Inhaled particles in the nanosize range can certainly deposit in all parts of the respiratory tract including the alveolar region of the lungs. Dependent upon the specific application, oral, dermal, and other routes of exposure are also possible for nanoparticles. Because of their small size, they may pass into cells directly through the cell membrane or penetrate the skin and distribute throughout the body once translocated to the blood circula-... 

Recently it has been shown that single-walled carbon nanotubes and fullerenes are capable of blocking cellular transmembrane ion channels [9]. Given global interest in the potential toxicity of nanomaterials, including C6o, the macrocyclic... 

Mesenchymal stem cells isolated from murine bone marrow were applied in a study designed to evaluate the molecular toxicity of hydroxyapatite nanoparticles (Remya et al., 2014). Hydroxyapatite nanoparticles (50 nm) were used to study the cytotoxicity, nanoparticle uptake, effect on cytoskeletal arrangement, oxidative stress response and apoptotic behaviour with the confluent cells as per standard protocols. The results of the MTT assay indicated that hydroxyapatite nanoparticles do not induce cytotoxicity up to 800 pg ml-1. It was also observed that apoptosis related to oxidative stress and reactive oxygen species (ROS) production following nanoparticle treatment was comparable to that of the control (cells without treatment). Hence, it can be concluded that mesenchymal stem cell in vitro cultures can be used as a model to evaluate the potential toxicity of nanomaterials. 

Monteiro-Riviere N, Cunningham M J (2006). Screening methods for assessing skin toxicity of nanomaterials. Toxicol. Sci. 90(1-S) 5. 

Evidence indicates exposure to nanoparticles can induce an inflammatory response in the CNS. For example, when a sample of mice were exposed to airborne particle matter, increased levels of pro-inflammatory cytokines (TNF-a IL-la), transcription factor, and nuclear factor-kappa beta (NF-k/3) were observed (114). TNF-a serves a neuroprotective function (115), but given certain pathogens TNF-a can be neurotoxic (116-120). IL-a activates cyclooxygenase (COX)-2, phospholipase A2, and inducible nitric oxide synthase (iNOS) activity, which are all associated with inflammation and immune response (121). IL-a is also partially responsible for increasing the permeability of the blood-brain barrier (122, 123). Thus, there is great interest in better understanding how nanoparticles enter the body and translocate as this will impact all organs and thus the toxicity of nanomaterials. 

The toxicity of nanomaterials is not well understood, and many commentators have expressed concern that the unique properties of nanomaterials maybe associated with unknown risks. Some of the concern is because of the ability of small particles to penetrate Hving tissue. There are conflicting study conclusions on whether inhaled nanoparticles may mimic the action of asbestos in the lungs. Some studies conclude that they do cause inflammation because they can reach the lung structures that exchange oxygen and carbon dioxide from the blood. However, other studies conclude that the results are equivocal. Similarly, titanium dioxide nanoparticles have been the subject of several studies to determine whether or not they can penetrate human skin when they are used in sunscreen formulations. While studies have shown that they do not penetrate beyond the outer layer of skin, the studies have been criticized because they were aU on intact, unabraded healthy adult skin, and so the risks in actual use may not be the same as indicated by those studies. In addition, many formulations contain moisturizers that are designed to penetrate skin, and the effects of these moisturizers on the skin penetration of titanium dioxide nanoparticles are unknown. ... 

In addition to size, the toxicity of nanomaterials depends on the shape, surface chemistry, surface charge, and chemical composition of the particle, among other characteristics. For example, nanoparticles of cobalt and manganese can enter cells, although salts of cobalt and manganese cannot. These nanoparticles are significantly more toxic than their salt counterparts. There is no scientific consensus about which characteristics are the most important determinants of toxicity. ... 

A. Nunes, K.T. Al-Jamal, K. Kostarelos, Therapeutics, imaging and toxicity of nanomaterials in the central nervous system, J. Control Release 161 (2) (2012) 290-306. 

Toxicity of biomaterials is usually viewed at both cellular and systemic levels. Toxicity at the cellular level, also known as cytotoxicity, is often caused by direct chemical toxicity of biomaterials, inflammatory reactions, or immune responses to biomaterials. Excessive or severe cytotoxicity, inflammatory reactions, or immune responses may lead to the toxicity remote from the initial insult and affecting organs or organ systems, which is defined as systemic toxicity. It is important to emphasize that toxicity caused by biomaterials is usually dose dependent. For cytotoxicity or nonimmune systemic toxicity, a threshold below which the biomaterial reveals little toxicity may be carefully determined by in vitro and in vivo studies. However, for immune systemic toxicity, determination of such a threshold is extremely difficult because immune responses are individual-dependent and largely affected by properties, dosage, and implantation location of the biomaterials. Toxicity of nanomaterials will be further discussed in this chapter. 

Size and shape Particle size has obvious effect on the toxicity of nanomaterials. An inverse relation between size and potential toxic effects is usually established small NPs offer a higher surface area and as a result a higher number of potentially reactive molecules in comparison with larger ones (given equal mass) [20]. Decreasing the size of NPs triggers the potential reactivity of these materials in an exponential way [21]... 

Maibach 2005 Rouse et al., 2007 Zhang and Monteiro-Riviere, 2008). So far there is not sufficient evidence to conclude that dermal absorption occurs for nanomaterials, and more importantly, whether or not nanomaterials can cause adverse local or systemic effects even if they do penetrate skin (Nanoderm, 2007 Nohynek et al., 2008 Borm et al., 2006 Tban et al., 2005 Gopee et al., 2007 Ryman-Rassmussen et al., 2007 Murray et al., 2009). In many cases, it will likely be necessary to evaluate the dermal penetration potential and dermal toxicity of nanomaterials on a case-by-case basis. 

Landsiedel, R., Ma-Hock, L, Hofmann, T, Wiemann, M., Strauss, V, Treumann, S., Wohlleben, W, Groters, S., Wiench, K. Van Ravenzwaay, B. 2014. Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials. Particle and Fibre Toxicology, 11, 16. 

Sharifi S, Behzadi S, Laurent S, Forrest ML, Stroeve P, Mahmoudi M. Toxicity of nanomaterials. Chem Soc Rev2012 41 2323 3. 

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