Journal of Applied Toxicology

Cover image for Vol. 35 Issue 10

October 2015

Volume 35, Issue 10

Pages 1073–1218

  1. Review Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Difficulties in establishing regulations for engineered nanomaterials and considerations for policy makers: avoiding an unbalance between benefits and risks (pages 1073–1085)

      Luis Guillermo Garduño-Balderas, Ismael Manuel Urrutia-Ortega, Estefany Ingrid Medina-Reyes and Yolanda Irasema Chirino

      Article first published online: 5 JUN 2015 | DOI: 10.1002/jat.3180

      The hazards of exposure to engineered nanomaterials (ENM) have led to some efforts to offer frameworks or guidelines to better maintain human health. Te aim o this work was to analyze the difficulties in establishing regulations for ENM, to discuss some considerations that may be helpful for policy makers and to provide suggestions for establishing normative regulations without decreasing ENM production.

    2. The potential health challenges of TiO2 nanomaterials (pages 1086–1101)

      Baoyong Sha, Wei Gao, Xingye Cui, Lin Wang and Feng Xu

      Article first published online: 14 JUL 2015 | DOI: 10.1002/jat.3193

      With the widespread application of nano-titanium dioxide (TiO2), the potential adverse impacts of nanomaterial exposure on humans have become a matter of concern. This paper reviews the potential exposure routes of nano-TiO2, the physico-chemical characterizations on nano-TiO2, risk evaluation of nanotoxicity and potential mechanisms of adverse effects, aiming to facilitate scientific assessments of health risks to nano-TiO2.

  2. Research Articles

    1. Top of page
    2. Review Articles
    3. Research Articles
    1. Investigation on cobalt-oxide nanoparticles cyto-genotoxicity and inflammatory response in two types of respiratory cells (pages 1102–1113)

      Delia Cavallo, Aureliano Ciervo, Anna Maria Fresegna, Raffaele Maiello, Paola Tassone, Giuliana Buresti, Stefano Casciardi, Sergio Iavicoli and Cinzia Lucia Ursini

      Article first published online: 13 MAR 2015 | DOI: 10.1002/jat.3133

      The increasing use of Co3O4 nanoparticles and the suggested genotoxicity highlight the need of further investigation. We evaluated cyto-genotoxic and inflammatory effects of Co3O4-NPs in human alveolar and bronchial cells. In alveolar cells direct and oxidative DNA damage were detected. In bronchial cells moderate cytotoxicity, direct DNA damage only at the highest concentration, and significant oxidative-inflammatory effects at lower concentrations were detected. The findings confirm the genotoxic-oxidative potential of Co3O4-NPs and the greater sensitivity of bronchial cells to cytotoxic-inflammatory effects.

    2. Particle uptake efficiency is significantly affected by type of capping agent and cell line (pages 1114–1121)

      Fan Zhang, Phillip Durham, Christie M. Sayes, Boris L. T. Lau and Erica D. Bruce

      Article first published online: 24 MAR 2015 | DOI: 10.1002/jat.3138

      Silver nanoparticles (AgNPs) capped with citrate, polyvinylpyrrolidone (PVP) and tannic acid were studied with human bronchoalveolar carcinoma and human colon adenocarcinoma cell lines to investigate the contribution of capping agents to their observed health impacts at realistic dose ranges. Results showed higher cellular uptake and rate from tannic acid capped AgNPs in both cell lines, and no observed toxicity from any type of the AgNPs treatment. Similar doses of silver ions, however, significantly altered cellular functionality.

    3. Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice (pages 1122–1132)

      Hailong Hu, Qian Guo, Changlin Wang, Xiao Ma, Hongjuan He, Yuri Oh, Yujie Feng, Qiong Wu and Ning Gu

      Article first published online: 31 MAR 2015 | DOI: 10.1002/jat.3150

      We explored endocrine effects of oral administration to mice of anatase titanium dioxide (TiO2) nanoparticles. Titanium levels increased in the liver, spleen, small intestine, kidney, and pancreas. ROS levels increased in serum and liver. Biochemical analyses showed plasma glucose significantly increased while there was no difference in insulin secretion. The pathway was TiO2 nanoparticle-increase ROS activated the inflammatory response and phosphokinase, and thus induced phosphorylation of JNK1 and p38 MAPK, resulting in insulin resistance and increasing plasma glucose in mice.

    4. Aluminium oxide nanoparticles induced morphological changes, cytotoxicity and oxidative stress in Chinook salmon (CHSE-214) cells (pages 1133–1140)

      Koigoora Srikanth, Amit Mahajan, Eduarda Pereira, Armando Costa Duarte and Janapala Venkateswara Rao

      Article first published online: 15 APR 2015 | DOI: 10.1002/jat.3142

      Chinook salmon (CHSE-214) cells exposed to aluminium oxide nanoparticles (Al2O3 NPs) induced dose dependent cytotoxicity. Morphology of CHSE-214 cells exposed to Al2O3 NPs were altered at 6, 12 and 24 h of exposure time. Reduction of SOD, CAT and GSH activity followed by an increase in GST and LPO was evident in CHSE-214 cells exposed to Al2O3 NPs. Thus our current work may serve as a base line study for future evaluation of toxicity studies using CHSE-214 cells.

    5. The surfactant dipalmitoylphophatidylcholine modifies acute responses in alveolar carcinoma cells in response to low-dose silver nanoparticle exposure (pages 1141–1149)

      A. Murphy, K. Sheehy, A. Casey and G. Chambers

      Article first published online: 16 APR 2015 | DOI: 10.1002/jat.3148

      Inhalation presents as the most common route of silver nanoparticle (AgNP) exposure. As such, its interaction with pulmonary surfactant may influence the biological response induced. Toxicological testing was performed on the A549 cell line and it demonstrated toxicity induced by AgNP exposure. Significant changes in acute responses including reactive oxygen species generation and inflammatory marker release was noted. It is postulated that the presence of dipalmitoylphosphatidylcholine interacts with AgNP producing a more reactive particle resulting in modification of acute responses at low dose exposures

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      Intracellular calcium levels as screening tool for nanoparticle toxicity (pages 1150–1159)

      Claudia Meindl, Tatjana Kueznik, Martina Bösch, Eva Roblegg and Eleonore Fröhlich

      Article first published online: 14 MAY 2015 | DOI: 10.1002/jat.3160

      Nano-sized materials may cause cytotoxicity. Negatively charged, neutral and positively charged polystyrene particles of different sizes and silica nanoparticles were used to study the role of size and surface properties on viability, membrane disruption, apoptosis, lysosome function, intracellular [Ca2+] levels and generation of oxidative stress. Small polystyrene particles and silica particles caused membrane damage and apoptosis with no preference of the surface charge. Increases in intracellular [Ca2+] levels could be used as a screening tool for cytotoxicity.

    7. Toxicogenomic responses of human liver HepG2 cells to silver nanoparticles (pages 1160–1168)

      Saura C. Sahu, Jiwen Zheng, Jeffrey J. Yourick, Robert L. Sprando and Xiugong Gao

      Article first published online: 26 MAY 2015 | DOI: 10.1002/jat.3170

      This study evaluated global gene expression profiles of human liver HepG2 cells exposed to silver nanoparticles (AgNPs). Exposure to 2.5 µg ml–1 20 nm AgNPs resulted in 811 altered genes after 4 h. Function and pathway analysis of the altered genes suggest that AgNP exposure may lead to increased oxidative stress and DNA damage in the cell and potentially result in genotoxicity and carcinogenicity.

    8. Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study (pages 1169–1178)

      Zheng-Mei Song, Ni Chen, Jia-Hui Liu, Huan Tang, Xiaoyong Deng, Wen-Song Xi, Kai Han, Aoneng Cao, Yuanfang Liu and Haifang Wang

      Article first published online: 23 JUN 2015 | DOI: 10.1002/jat.3171

      Titanium dioxide nanoparticles (TiO2 NPs) are widely used in food products; therefore, understanding their effect and absorption on the intestinal barrier is vital. Bioeffects of two native and digestion fluids or bovine serum albumin pretreated TiO2 NPs were studied on the Caco-2 cells and monolayer. The results indicate that all TiO2 NPs were non-toxic to the differentiated Caco-2 cells and monolayer, differentiation of cells and protein coating impeded the cellular uptake of NPs, and it was difficult for NPs to traverse through the Caco-2 monolayer.

    9. Chromium oxide nanoparticle-induced genotoxicity and p53-dependent apoptosis in human lung alveolar cells (pages 1179–1188)

      Violet Aileen Senapati, Abhishek Kumar Jain, Govind Sharan Gupta, Alok Kumar Pandey and Alok Dhawan

      Article first published online: 18 JUN 2015 | DOI: 10.1002/jat.3174

      The use of Chromium oxide (Cr2O3) nanoparticles (NPs) in industrial products has boomed but the possible adverse effect to human health is unclear. Therefore, in the present study the genotoxic and apoptotic effect of Cr2O3 NPs in human lung epithelial cells (A549) was investigated. Cr2O3 NPs led to DNA damage mediated by reactive oxygen species. Furthermore, the immunoblot analysis revealed an increased expression of BAX, phosphorylated p53, cytochrome-c and caspase-3 with decrease in Bcl-2 levels thereby leading to mitochondria-mediated apoptosis.

    10. Analysis of cytotoxic effects of silver nanoclusters on human peripheral blood mononuclear cells ‘in vitro (pages 1189–1199)

      Sandra Teresa Orta-García, Germán Plascencia-Villa, Angeles Catalina Ochoa-Martínez, Tania Ruiz-Vera, Francisco Javier Pérez-Vázquez, J Jesús Velázquez-Salazar, Miguel José Yacamán, Hugo Ricardo Navarro-Contreras and Iván N. Pérez-Maldonado

      Article first published online: 17 JUN 2015 | DOI: 10.1002/jat.3190

      The antimicrobial properties of silver nanoparticles (AgNPs) have made these particles one of the most used nanomaterials in consumer products. Therefore, an understanding of the interactions (unwanted toxicity) between nanoparticles and human cells is of significant interest. The aim of this study was to assess the in vitro cytotoxicity effects of silver nanoclusters (AgNC, < 2 nm diameter) on peripheral blood mononuclear cells (PBMC).

    11. In vitro study of biocompatibility of a graphene composite with gold nanoparticles and hydroxyapatite on human osteoblasts (pages 1200–1210)

      Liana Crisan, Bogdan Crisan, Olga Soritau, Mihaela Baciut, Alexandru Radu Biris, Grigore Baciut and Ondine Lucaciu

      Article first published online: 20 APR 2015 | DOI: 10.1002/jat.3152

      The purpose of this study was to evaluate the biocompatibility of composites consisting of different proportions of graphene in combination with gold (Au) nanoparticles and nanostructured hydroxyapatite (HA) on osteoblasts. The cytocompatibility study was performed using the fluorescein diacetate assay. The most favorable composites for cell adhesion and proliferation were HA, Au/HA and Au/HA composites with 1.6% and 3.15% concentration of graphenes. The presence of graphene in the substrate composition induced an increased level of intracellular osteopontin and cytoskeleton reorganization.

    12. Accumulation and toxicity of intravenously-injected functionalized graphene oxide in mice (pages 1211–1218)

      Kai-Ping Wen, Ying-Chieh Chen, Chia-Hui Chuang, Hwan-You Chang, Chi-Young Lee and Nyan-Hwa Tai

      Article first published online: 23 JUN 2015 | DOI: 10.1002/jat.3187

      Graphene and its functionalized derivatives have recently emerged as interesting nanomaterials in biomedicine. In this study, the long-term in vivo biodistribution of intravenously injected nanographene oxide (NGO) functionalized with poly sodium 4-styrenesulfonate (PSS) was systematically examined and the potential toxicity over 6 months of NGO-PSS nanoparticles was investigated. Our results showed that the nanoparticles mainly accumulate in the lung, liver and spleen, which result in acute liver injury and chronic inflammation as evidenced by blood biochemistry results and histological examinations.