In this study, we focused on MPO, which has the ability to directly damage cells via oxidative stress, and exam- ined its usefulness as a biomarker for evaluating the pulmonary toxicity of nanoparticles, using inhaled che- micals including nanomaterials which were classified as having pulmonary toxicity. The results of the measure- ment of MPO protein concentration reflected that the most accurate ranking of pulmonary toxicity in both intratracheal instillation and inhalation exposure was at 1 month after exposure. MPO correlated with inflamma- tory cells, other inflammatory chemokines, and an oxi- dative stress marker, and it was thought that MPO was related to lung disorder due to pulmonary inflammation by nanomaterials. Taken together, we suggest that MPO can be a useful biomarker for the ranking of pulmonary toxicity of nanomaterials in both intratracheal instilla- tion and inhalation exposure.
Nanomaterials are structures with characteristic dimensions of 1-100 nanometers (nm). The word “nano” derives from the Greek word meaning extremely small. Over the past ten years, nanomaterials have been the subject of interest. Nanomaterials can consist of ceramics, metals, polymeric materials, or composite materials. The rapid development of nanotechnology enables a variety of diagnostic applications by utilizing the optical, electrical, magnetic and mechanical characteristics of different types of nanoparticles (NP). In addition, functionalized NP may be used as efficient and highly active drugs for specific target organs or cells that overcome problems of non-specific and unwanted interactions. NP are not only applied in biomedical applications, but also for industrial applications due to their extremely small size. As the extensive utilization of NP increases, the risk for manufacturers and consumers and exposure to NP has raised concerns about their health effects. Furthermore, the understanding of mechanism of NP interaction with biological systems can help improve NP drug delivery. Currently, little is known regarding the safety and use of NP and their interaction with in vitro and in vivo systems. This thesis will focus on NP toxicity of Multi- walled carbon nanotubes (MWCNT), quantum dots (QD), and functionalized SWCNT and fullerene, their interaction with skin and skin cells, as well as the cellular uptake mechanisms. NP exposure can occur through oral, nasal, pulmonary, dermal, ocular and possibly other routes. Skin is the largest organ of the body and due to its large surface area, it could be one of the primary targets for NP entry into the body. Skin is generally composed of two layers: epidermis and the dermis. The epidermis located on the upper part of skin contains the stratum corneum (SC). This non-viable layer is the barrier that protect skin from light, dehydration and invasions by toxins, bacteria or NP. In chapter 3, we investigated QD penetration in porcine skin.
To promote the collection of relevant data for the safety assessment of a representative set of NMs, the Organi- sation for Economic Co-operation and Development Working Party on Manufactured Nanomaterials (OECD WPMN) has launched a Sponsorship Programme for the testing of manufactured nanomaterials [6, 7]. This programme further aims at establishing the role of 3Rs methods for NM testing . With inhalation generally being one of the main routes of NM exposure both for workers and consumers [8, 9], the WPMN has proposed a short-term rat inhalation study (STIS ) as a suitable test method to reduce and refine repeated-dose sub-acute inhalation toxicity testing. The STIS provides informa- tion on early elements of NM-induced pathogenesis as well as on the reversibility, persistence or progression of effects. Furthermore, NM lung burden and potential for extra-pulmonary translocation may be investigated in the STIS [9–11].
thetic amorphous silica, zinc oxide, zirconium dioxide, and multiwall carbon nanotubes. The studies included in the case report were not identical in regard to experimental conditions, such as animal strains, physico-chemical char- acteristics of the test materials, or preparation of the test material. Furthermore, only a limited number of sub- chronic and chronic studies were available against which to compare the results of the STIS. Nevertheless, the ranking of the spectrum of nanomaterials in regard to their potential to induce adverse effects was concordant for the NOAECs determined in the STIS and in the corresponding subchronic and chronic studies, and it was also consistent with the ranking set up in the present study. Furthermore, the STIS were able to reveal the progression or regression of adverse effects, to indi- cate translocation of materials to extra-pulmonary organs and to provide early indications of effects that only de- velop over time and hence only become fully pro- nounced in longer-term studies .
Abstract: Nanomaterials are the subject of intense research, focused on their synthesis, modification, and biomedical applications. Increased nanomaterial production and their wide range of applications imply a higher risk of human and environmental exposure. Unfortunately, neither environmental effects nor toxicity of nanomaterials to organisms are fully understood. Cost-effective, rapid toxicity assays requiring minimal amounts of materials are needed to establish both their biomedical potential and environmental safety standards. Drosophila exemplifies an efficient and cost-effective model organism with a vast repertoire of in vivo tools and techniques, all with high-throughput scalability and screening feasibility throughout its life cycle. Here we report tissue specific nanomaterial assessment through direct microtransfer into target tissues. We tested several nanomaterials with potential biomedical applications such as single-wall carbon nanotubes, multiwall carbon nanotubes, silver, gold, titanium dioxide, and iron oxide nanoparticles. Assessment of nanomaterial toxicity was conducted by evaluating progression through developmental morphological milestones in Drosophila. This cost-effective assessment method is amenable to high-throughput screening.
vii)To make a balanced approach between technology development and addressing risk issues we have to argue that research related to toxicity and risk assessment must be undertaken once the applicability of specific nano-applications are ascertained, especially when the prototype of the product has been developed and is available for field testing.
Metal oxide NPs also offer a wide range of applications in biomedicine like the studies of pharmacokinetics, tissue distribution, drug delivery, magnetic resonance imaging, plasmid DNA transfer, bactericidal agents etc. . Among a variety of metal oxides available, iron oxide nanomaterial has proved to provide a wide variety of applications. The surface engineered iron oxide NPs have been applied in cell labelling, cell repair, cell separation, detoxification of biological fluids, tissue repair, MRI, drug delivery etc. . In addition, gold coated iron oxide NPs serve both as MRI contrast agents and nano-heaters for therapies like cellular hyperthermia or thermo-responsive drug delivery . A broad range of metal oxide nanomaterials show antibacterial properties which is attributed to their production of reactive oxygen species and induction of oxidative stress. Gold, Iron
In present days, the nanomaterials have been a core focus of nanoscience and nanotechnology which is an ever- growing multidisciplinary field of study attracting tremendous interest, investment and have entered a commercial application, exploration and effort in world wide research and development . Nanoporous materials as a subset of nanostructured materials possess unique surface, structural, and bulk properties that underline their important uses in various fields such as ion exchange, separation, catalysis, sensor, biological molecular isolation and purifications. Nanoporous materials are also of scientific and technological importance because of their vast ability to adsorb and interact with atoms, ions and molecules on their large interior surfaces and in the nano- sized pore space. These offer new opportunities in areas of including chemistry, guest-host synthesis and molecular manipulations and reaction in the nanoscale for making nanoparticles, nanowires and other quantum nanostructures [3, 4].
MicroRNAs (miRNAs), a class of non-protein-coding and small RNAs, play a critical role in post- transcriptional regulation of gene expression, thus having been regarded as important biomarkers for many diseases. In the past decade, electrochemical biosensors have been employed widely for the highly sensitive and multiplexed detection of miRNAs. In particular, integrating into nanomaterials further improve the performances of the developed assays. This review mainly focuses on the achievement in the use of nanomaterials in electrochemical biosensors for facile and sensitive miRNAs detection, which will be useful toward understanding the methodology of assays and proposing more effective and practical electrochemical biosensors for miRNAs detection.
Another variable factor that could affect the trans- formation of iENMs in food and during digestion (and thus their bioactivity, toxicity and biokinetics) is the method by which the iENMs are incorporated into the food model. In the work presented here, we chose to first create a monodisperse suspension in DI water and then incorporate that into our liquid food model by sim- ply vortexing. However, a number of alternative methods are possible. For example, the dry powder ENM might be simply added directly to the food and the combination either stirred or vortexed to mix. The most appropriate method might be that which is actually used by food man- ufacturers to incorporate iENMs into their products. However, these methods may not be easy to ascertain. Moreover, since a given iENM may be used in a number of different foods in terms of consistency, composition, and preparation method. Thus, standardization of iENM- food incorporation methods could prove difficult.
Grouping of nanoforms of a substance with the aim to transfer available data on a hazard endpoint from one nanoform to another one is one major tool to address the challenges in the assessment of countless nanomaterials. While the understanding of grouping of nanomaterials for comparable toxic effects on human health consider- ably progressed, analogous principles for environmental health are still at the beginning. This evaluation tried to build and verify grouping hypothesis for selected nano- forms of the same substances based on available data from two research projects to investigate the relevance of physical chemical properties as indicated, e.g., by ECHA guidance. Even though it was not possible to deduce a final conclusion for valid grouping for the considered cases yet, the results support the guidance given by ECHA that, beside key parameters like solubility, shape, and agglomeration, other aspects like interaction with the investigated organism need to be taken into account. So far, assumptions on aspects relevant for grouping and analogy approaches for nanomaterials on environmental endpoints for regulatory use mainly based on educated guesses deduced from a synopsis of available data on environmental fate and effects. These are now substanti- ated with strategically collected experimental data. Still, the results indicate that the prediction of the ecotoxico- logical potential of nanoforms remains very challeng- ing due to the interplay of various intrinsic and extrinsic properties of nanoforms and thereby limited.
Some uncertainties also remain because our experi- mental data-set did not allow to provide a clear dose-response pattern of toxicity. That may had an im- pact on the accuracy of our comparisons. For example in vivo, there was a difference of a factor of ten between each dose tested; this might prevent us to determine ac- curate LOAELs and dose intervals. This is particularly true because the pro-inflammatory effects were observed at the highest dose tested. Although using intermediary doses might have enabled to determine more precisely LOAELs and critical dose intervals, this has no impact on our general conclusions regarding comparison of bio- logical activation levels between the different exposure methods used in our study: regardless the criterion of comparison used, the in vivo methodology remains the most sensitive one in our study, to predict potential ad- verse effects after acute exposure to poorly soluble NMs. Regarding NM rankings, we observed that it was difficult to use LOAELs to rank NMs in function of each expos- ure methodology used and that determining dose inter- vals using benchmark dose-response modeling was very important for this purpose. However, because the data-set quality used in our study was not optimal, the dose intervals determined were too large to provide clear and reliable comparisons of NM rankings between each methodology used. To perform in vivo - in vitro com- parisons we thus recommend to test more doses and to reduce the interval between each doses, in order to de- termine more accurate dose intervals.
2) Surface Coatings Of Electrical Goods: Nanomaterials are now a days used as surface coatings in certain electrical goods because they have anti-microbial properties. These coatings used for anti microbial properties mainly contain silver nano-particles. Silver has natural anti-bacterial and anti-fungal properties and silver engineered into nano-particle size increases the surface area in contact with micro-organisms which, in turn, improves its bacterial and fungicidal effectiveness (Nanotech Plc 2006). Some commonly used products include refrigerators, vacuum cleaners, washing machines, mobile phones and computer mice.