During the past 20 years, improvements in nanoscale materials synthesis and characterization have given scientists great control over the fabrication of materials with features between 1 and 100 nm, unlocking many unique size-dependent properties and, thus, promising many new and/or improved technologies. Recent years have found the integration of such materials into commercial goods; a current estimate suggests there are over 800 nanoparticle-containing consumer products (The Project on Emerging Nanotechnologies Consumer Products Inventory, , accessed Oct. 2008), accounting for 147 billion USD in products in 2007 (Nanomaterials state of the market Q3 2008: stealth success, broad impact, Lux Research Inc., New York, NY, 2008). Despite this increase in the prevalence of engineered nanomaterials, there is little known about their potential impacts on environmental health and safety. The field of nanotoxicology has formed in response to this lack of information and resulted in a flurry of research studies. Nanotoxicology relies on many analytical methods for the characterization of nanomaterials as well as their impacts on in vitro and in vivo function. This review provides a critical overview of these techniques from the perspective of an analytical chemist, and is intended to be used as a reference for scientists interested in conducting nanotoxicological research as well as those interested in nanotoxicological assay development.

Analytical methods to assess nanoparticle toxicity

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.

Orthopaedic metals and their potential toxicity in the arthroplasty patient: A review of current knowledge and future strategies.

Nanotechnology has revolutionized gene therapy, diagnostics and environmental remediation. Their bulk production, uses and disposal have posed threat to the environment. With the appearance of these nanoparticles in the environment, their toxicity assessment is an immediate concern. This review is an attempt to summarize the major techniques used in cytotoxity determination. The review also presents a detailed and elaborative discussion on the toxicity imposed by different types of nanoparticles including carbon nanotubes, gold nanoparticles, silver nanoparticles, quantum dots, fullerenes, aluminium nanoparticles, zinc nanoparticles, iron nanoparticles, titanium nanoparticles and silica nanoparticles. It discusses the in vitro and in vivo toxological effects of nanoparticles on bacteria, microalgae, zebrafish, crustacean, fish, rat, mouse, pig, guinea pig, human cell lines and human. It also discusses toxological effects on organs such as liver, kidney, spleen, sperm, neural tissues, liver lysosomes, spleen macrophages, glioblastoma cells, hematoma cells and various mammalian cell lines. It provides information about the effects of nanoparticles on the gene-expression, growth and reproduction of the organisms.

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In vitro and in vivo toxicity assessment of nanoparticles

Surface chemistry influences cancer killing effect of TiO2 nanoparticles.

From 1916 to 2011, an estimated total of 165 050 000 metric tons of titanium dioxide (TiO2) pigment were produced worldwide. Current safety regulations on the usage of the TiO2 pigment as an inactive ingredient additive in human food are based on legislation from 1969 and are arguably outdated. This article compiles new research results to provide fresh data for potential risk reassessment. However, even after 45 years, few scientific research reports have provided truly reliable data. For example, administration of very high doses of TiO2 is not relevant to daily human uptake. Nevertheless, because dose makes the poison, the literature provides a valuable source for understanding potential TiO2 toxicity after oral ingestion. Numerous scientific articles have observed that TiO2 can pass and be absorbed by the mammalian gastrointestinal tract; can bioconcentrate, bioaccumulate, and biomagnify in the tissues of mammals and other vertebrates; has a very limited elimination rate; and can cause histopathological and physiological changes in various organs of animals. Such action is contrary to the 1969 decision to approve the use of TiO2 as an inactive ingredient in human food without an established acceptable daily intake, stating that neither significant absorption nor tissue storage following ingestion of TiO2 was possible. Thus, relevant governmental agencies should reassess the safety of TiO2 as an additive in human food and consider establishing an acceptable maximum daily intake as a precautionary measure. Integr Environ Assess Manag 2015;11:10–20. © 2014 The Author. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.

https://setac.onlinelibrary.wiley.com/doi/epdf/10.1002/ieam.1571

Critical Review of Public Health Regulations of Titanium Dioxide, a Human Food Additive

Different metals are increasingly being used to manufacture implants, especially in the fields of dentistry and orthopedics. No metal or alloy is completely inert in vivo. The metal and the organic fluids interact releasing, for example, metallic products. Several hypotheses regarding the probable dissemination routes of titanium have been postulated, but its valence, the organic nature of its ligands and its potential toxicity have yet to be established. In a previous experimental study we demonstrated that i.p. injected titanium and zirconium oxides disseminate and deposit in organs such as liver and lung. The aim of this work was to study the eventual participation of blood cells in the transport mechanism of titanium employing the intraperitoneal injection of titanium oxide in rats as the experimental model. Twenty male Wistar rats, x: 100 g body weight, were intraperitoneally injected with 16x10(3) mg/kg b.w. of TiO(2) in saline solution. Blood samples were taken by heart puncture at 3 and 6 months; blood smears were performed and stained with safranin evidencing monocytes containing titanium particles. The results obtained in this study would indicate that one of the ways in which titanium is disseminated is through the blood stream, via blood cells.

Titanium transport through the blood stream. An experimental study on rats.

Objective To analyze the bioreduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) on a per cell basis and evaluate its modulation as a function of different stages of cell metabolism. Study design Following MTT bioreduction, total optical density (TOD), cell area and specific activity (TOD/area) of V79 cells and cultured macrophages were recorded for individual cells by means of digital image analysis. The effect of different serum (0-10% vol/vol) or genistein (0-100 microM) concentrations was used to modulate the MTT-specific activity response. Results As cells in culture are heterogeneous in cell size, the contribution of each cell to the total amount of formazan formed per dish is variable. The production of formazan per cell as a result of MTT bioreduction was found to be proportional to cell size. Conclusion Specific MTT-reducing activity was analyzed in phagocytes and nonphagocyte cells, revealing the utility of this variable in evaluating the MTT assay at the single-cell level.

Cell-based quantitative evaluation of the MTT assay.

Uranium is the heaviest naturally occurring element found in the Earth’s crust. It is an alphaemitter radioactive element that present both radiotoxicant and chemotoxicant properties. Uranium is present in environment as a result of natural deposits and releases by human applications (mill tailings, nuclear industry and military army). The release of uranium or its by-products into the environment (air, soil and water) presents a threat to human health and to the environment as a whole. Uranium can enter the body by ingestion, inhalation or dermal contact yet, the primary route of entry into the body is inhalation. Research on inhaled, ingested, percutaneous and subcutaneous industrial uranium compounds has shown that solubility influences the target organ, the toxic response, and the mode of uranium excretion. The overall clearance rate of uranium compounds from the lung reflects both mechanical and dissolution processes depending on the morphochemical characteristics of uranium particles. In this review we emphasize on one of the principal physical characteristics of uranium particles, its size. As is known, based on uranium chemical composition, three different kinds are defined: natural, enriched (EU) and depleted (DU) uranium. The radiological and chemical properties of natural uranium and DU are similar. In fact, natural uranium has the same chemotoxicity, but its radiotoxicity is 60% higher. DU, being a waste product of uranium enrichment, has several civilian and military applications. Lately, it was used in international military conflicts (Gulf and recently as the Balkan Wars) and was claimed to contribute to health problems. Herein, we reviewed the toxicological data in vivo and in vitro on both natural and depleted uranium and renewed efforts to understand the intracellular metabolism of this heavy toxic metal. The reader will find this chapter divided in three sections. The first section, describes the presence of the uranium in the environment, the routes of entrance to the body and its impact on health. The second section which is committed to uranium cytotoxicity and its mechanism of action stressed on the oxidative metabolism and a third section dedicated to the effect of different compounds, mainly bisphosphonates, as substances with the ability to restrain uranium toxicity.

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Debora R. Tasat

Papers

Titanium transport through the blood stream. An experimental study on rats.

Cell-based quantitative evaluation of the MTT assay.

Intracellular Metabolism of Uranium and the Effects of Bisphosphonates on Its Toxicity