Journal of Applied Toxicology

Cover image for Vol. 34 Issue 4

April 2014

Volume 34, Issue 4

Pages 319–440

  1. Review Article

    1. Top of page
    2. Review Article
    3. Research Articles
    4. Short Communication
    1. Foamy macrophage responses in the rat lung following exposure to inhaled pharmaceuticals: a simple, pragmatic approach for inhaled drug development (pages 319–331)

      David J. Lewis, Thomas C. Williams and Steven L. Beck

      Article first published online: 6 NOV 2013 | DOI: 10.1002/jat.2950

      A significant factor in attrition during the development of respiratory medicines is the induction of foamy macrophage responses, particularly in rats. We propose a simple classification, which allows important distinctions to be made between phenotypes, aetiologies and adversity. Simple foamy macrophage responses are considered non-adverse, whereas more complex ones are designated as adverse. It is the aim of this review to help clarify, what is in fact a relatively simple, predictable, easily interpretable, commonly induced change.

  2. Research Articles

    1. Top of page
    2. Review Article
    3. Research Articles
    4. Short Communication
    1. Short-term splenic impact of single-strand DNA functionalized multi-walled carbon nanotubes intraperitoneally injected in rats (pages 332–344)

      Simona Clichici, Alexandru Radu Biris, Cornel Catoi, Adriana Filip and Flaviu Tabaran

      Article first published online: 16 MAY 2013 | DOI: 10.1002/jat.2883

      We investigated the effects of single-strand DNA-multi-walled carbon nanotubes (ss-DNA-MWCNT) on the rat spleen, after intraperitoneal (i.p.) administration. Carbon nanotubes were detected in the spleen using Raman spectroscopy, histopathologic examination, confocal microscopy and transmission electron microscopy (TEM), at different time points after administration. The dynamics of oxidative and nitrosative stress parameters, pro-inflammatory cytokines and the number of cells expressing caspase 3 and proliferating cell nuclear antigen were assessed. Our results indicate that MWCNT translocate progressively in the spleen, determine lymphoid hyperplasia and transient alterations of oxidative stress and inflammation.

    2. Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL-3A cells and Sprague–Dawley rats (pages 345–356)

      Baoyong Sha, Wei Gao, Shuqi Wang, Xingchun Gou, Wei Li, Xuan Liang, Zhiguo Qu, Feng Xu and Tian Jian Lu

      Article first published online: 22 JUL 2013 | DOI: 10.1002/jat.2900

      Nanotoxicity assessment of titanium dioxide (TiO2) under oxidative stress (OS) conditions is a novel field. Compared with nanomaterials (NMs) exposure only, OS conditions and nano-TiO2 synergistically reduced BRL-3A cell viabilities and resulted in the rapid G0/G1 to S phase transition and G2/M arrest. Interactions between OS conditions and nano-TiO2 induced obvious pathological changes in rat livers and enhanced the activities of liver damage biomarkers.

    3. Comparison of toxicity of different nanorod-type TiO2 polymorphs in vivo and in vitro (pages 357–366)

      Eun-Jung Park, Gwang-Hee Lee, Hyun-Woo Shim, Jae-Ho Kim, Myung-Haing Cho and Dong-Wan Kim

      Article first published online: 7 OCT 2013 | DOI: 10.1002/jat.2932

      In this study, we characterized two types of TiO2 nanorods, anatase and brookite, and compared their toxicity in vivo and in vitro. As results, the surface area acts as an important factor which depends on toxicity of nanorod type-TiO2 nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the type of cells tested, and that the assembly of autophagosome-like vacuoles is a critical part of the cellular response to nanoparticle exposure.

    4. Cytotoxicity of silica nanoparticles on HaCaT cells (pages 367–372)

      Hao Liang, Chan Jin, Ying Tang, Fude Wang, Chunwang Ma and Yongji Yang

      Article first published online: 24 OCT 2013 | DOI: 10.1002/jat.2953

      Spherical SiO2 nanoparticles (SiO2 NPs) with a 50 nm diameter were found to be readily internalized into HaCaT cells and localized in the cytoplasm, lysosomes, and autophagosomes. Decreased cell viability and damaged cell membrane integrity showed the cytotoxicity of SiO2 NPs. Significant GSH depletion and ROS generation which reduced the cellular antioxidant level could be the major factor of cytotoxicity induced by SiO2 NPs.

    5. Evaluation of cytotoxic, oxidative stress and genotoxic responses of hydroxyapatite nanoparticles on human blood cells (pages 373–379)

      Hasan Turkez, Mokhtar I. Yousef, Erdal Sönmez, Başak Togar, Feray Bakan, Piera Sozio and Antonio Di Stefano

      Article first published online: 6 NOV 2013 | DOI: 10.1002/jat.2958

      The present study was designed to investigate genotoxic and cytotoxic effects and oxidative damage of increasing concentrations of hydroxyapatite nanoparticles (HAP NPs) in primary human blood cell cultures. The results of MTT and LDH assays showed that the higher concentrations of HAP NPs decreased cell viability and altered oxidative status in cultured human blood cells. HAP NPs caused genotoxicity. In conclusion, present results showed that HAP NPs had dose-dependent effects on inducing oxidative damage, genotoxicity and cytotoxicity in vitro.

    6. Assessing carbon-encapsulated iron nanoparticles cytotoxicity in Lewis lung carcinoma cells (pages 380–394)

      Ireneusz P. Grudzinski, Michal Bystrzejewski, Monika A. Cywinska, Anita Kosmider, Magdalena Poplawska, Andrzej Cieszanowski, Zbigniew Fijalek, Agnieszka Ostrowska and Andrzej Parzonko

      Article first published online: 11 NOV 2013 | DOI: 10.1002/jat.2947

      The cytotoxic effect of carbon-encapsulated iron nanoparticles (CEINs) was examined in Lewis lung carcinoma cells. The CEIN samples were synthesized using a carbon arc route, and the as-synthesized CEINs were characterized and examined as raw and purified nanomaterials containing the carbon surface modified with acidic groups. Our results shed new light on the rational design of CEINs, as their geometry, hydrodynamic and, in particular, surface characteristics are important features in selecting CEINs as future magnetic nanomaterials for nanomedicine applications.

    7. Comet assay reveals no genotoxicity risk of cationic solid lipid nanoparticles (pages 395–403)

      Slavomira Doktorovova, Amélia M. Silva, Isabel Gaivão, Eliana B. Souto, João P. Teixeira and Paula Martins-Lopes

      Article first published online: 15 NOV 2013 | DOI: 10.1002/jat.2961

      Cationic solid lipid nanoparticles (cSLN) are colloidal carriers for genes or drugs. Internalization, cell viability (alamar blue assay) and the genotoxic potential (alkaline comet assay) of three cSLN formulations were evaluated in HepG2 and Caco-2 cells. 0.01 mg ml–1 cSLN unaffected cell viability, but 1.0 mg ml–1 significantly decreased it, with HepG2 affected more. DNA damage was not significantly increased by 0.1 mg ml–1 cSLN but damage was observed at 1.0 mg ml–1 cSLN-C. No genotoxicity is to be expected at concentrations that do not reduce cell viability.

    8. Interaction between silver nanoparticles of 20 nm (AgNP20) and human neutrophils: induction of apoptosis and inhibition of de novo protein synthesis by AgNP20 aggregates (pages 404–412)

      Michelle Poirier, Jean-Christophe Simard, Francis Antoine and Denis Girard

      Article first published online: 15 NOV 2013 | DOI: 10.1002/jat.2956

      The aim of this study was to investigate the potential effect of AgNP20 on human neutrophil cell biology. AgNP20 were found to induce human neutrophil apoptosis by a de novo protein synthesis-dependent and reactive oxygen species-independent mechanism.

    9. Cytotoxicity and ROS production of manufactured silver nanoparticles of different sizes in hepatoma and leukemia cells (pages 413–423)

      Alicia Avalos, Ana Isabel Haza, Diego Mateo and Paloma Morales

      Article first published online: 15 NOV 2013 | DOI: 10.1002/jat.2957

      Nanotechnology allows for an efficient exploitation of the antimicrobial properties of silver (Ag) using silver in the form of NPs. The goal of the present work was to study how AgNPs of different sizes interact with two different tumoral human cell lines in order to understand the impact of such nanomaterials on cellular biological functions. In addition, glutathione content, superoxide dismutase activity and reactive oxygen species generation were used to evaluate feasible mechanisms by which AgNPs exerted its toxicity.

    10. Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells (pages 424–435)

      Yi-Xin Yang, Zheng-Mei Song, Bin Cheng, Kun Xiang, Xin-Xin Chen, Jia-Hui Liu, Aoneng Cao, Yanli Wang, Yuanfang Liu and Haifang Wang

      Article first published online: 3 DEC 2013 | DOI: 10.1002/jat.2962

      Silica nanoparticles (NPs) have been widely used in food products as an additive. However, their toxicity and safety to the human body and the environment remain unclear. We thus studied the toxicity of food additive silica NPs to gastrointestinal cells. The results indicate that four silica NPs are safe at concentrations lower than 100 µg ml–1. At a higher concentration and longer exposure period (> 24 h), silica NPs change the cell cycle and inhibit cell growth.

  3. Short Communication

    1. Top of page
    2. Review Article
    3. Research Articles
    4. Short Communication
    1. Integrated testing and assessment approaches for skin sensitization: a commentary (pages 436–440)

      David W. Roberts and Grace Y. Patlewicz

      Article first published online: 10 OCT 2013 | DOI: 10.1002/jat.2943

      This short communication addresses a recently published Bayesian approach to an integrated testing strategy for skin sensitization. The main findings of the Bayesian study are consistent with our chemistry-based approach. Whereas the Bayesian approach currently predicts only potency categories, the chemistry-based approach can often predict numerical potency values per se. Nevertheless, the Bayesian approach may have potential for those chemicals such as pro-electrophiles requiring metabolic activation, where a chemistry modeling approach cannot provide a complete answer.