Journal of Applied Toxicology

Cover image for Vol. 36 Issue 4

April 2016

Volume 36, Issue 4

Pages 479–626

  1. Issue information - TOC

    1. Top of page
    2. Issue information - TOC
    3. Review articles
    4. Research articles
    1. Issue information - TOC (pages 479–482)

      Article first published online: 11 FEB 2016 | DOI: 10.1002/jat.3238

  2. Review articles

    1. Top of page
    2. Issue information - TOC
    3. Review articles
    4. Research articles
    1. The role of intramolecular self-destruction of reactive metabolic intermediates in determining toxicity (pages 483–500)

      Andreas Svennebring

      Article first published online: 6 NOV 2015 | DOI: 10.1002/jat.3248

      Intermolecular reactions tend to dominate over intramolecular alternatives when both alternatives are possible. Consequently, for reactive metabolites of xenobiotics, intramolecular quenching by moieties adjacent to a toxicophore may reduce toxicity related to reactive intermediates. In two demonstrative cases, nitrobenzenes and aryl amine drugs, the toxicity characteristic of the toxicophore is absent for drugs that can undergo intramolecular quenching.

  3. Research articles

    1. Top of page
    2. Issue information - TOC
    3. Review articles
    4. Research articles
    1. You have full text access to this OnlineOpen article
      Long-term retention of pristine multi-walled carbon nanotubes in rat lungs after intratracheal instillation (pages 501–509)

      Naohide Shinohara, Tetsuya Nakazato, Kumiko Ohkawa, Moritaka Tamura, Norihiro Kobayashi, Yasuo Morimoto, Takako Oyabu, Toshihiko Myojo, Manabu Shimada, Kazuhiro Yamamoto, Hiroaki Tao, Makoto Ema, Masato Naya and Junko Nakanishi

      Article first published online: 29 DEC 2015 | DOI: 10.1002/jat.3271

      Well-dispersed pristine MWCNTs were administered to rats at doses of 0.20 or 0.55 mg via intratracheal instillation, and investigated clearance over a 12-month observation period. Approximately 30% of administrated MWCNTs may have been cleared by bronchial ciliary motion within 24 h of administration. After that, the pulmonary MWCNT burden did not decrease significantly over time for up to 364 days after instillation, suggesting that MWCNTs were not readily cleared from the lung. MWCNTs were not detected in the liver or brain within the 364-day study period.

    2. Rhamnose-coated superparamagnetic iron-oxide nanoparticles: an evaluation of their in vitro cytotoxicity, genotoxicity and carcinogenicity (pages 510–520)

      Alessandro Paolini, Constança Porredon Guarch, David Ramos-López, Joaquín de Lapuente, Alessandro Lascialfari, Yannick Guari, Joulia Larionova, Jerome Long and Rosanna Nano

      Article first published online: 28 DEC 2015 | DOI: 10.1002/jat.3273

      In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with rhamnose derivative. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles and of concern cytotoxicity, a 35% of cell death at a maximum concentration due mainly to mitochondrial damages, was evidenced. This cytotoxic behavior, along with a high uptake ability could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future magnetic fluid hyperthermia (MFH) therapeutic treatments.

    3. Flow cytometric evaluation of the contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells (pages 521–531)

      Saura C. Sahu, Joyce Njoroge, Steven M. Bryce, Jiwen Zheng and John Ihrie

      Article first published online: 6 JAN 2016 | DOI: 10.1002/jat.3276

      Recently, we reported the genotoxicity of 20 nm nanosilver evaluated by the FCMN assay. In this study, we evaluated the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge and obtained from the same commercial source using the same experimental conditions, human-derived cells (HepG2 and Caco2) and genotoxic endpoint (FCMN) used for the 20 nm silver. Also, in this study, we evaluated the contribution of ionic silver to the genotoxic potential of nanosilver using silver acetate as the representative ionic silver.

    4. Contribution of ionic silver to genotoxic potential of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by the cytokinesis-block micronucleus assay (pages 532–542)

      Saura C. Sahu, Shambhu Roy, Jiwen Zheng and John Ihrie

      Article first published online: 27 JAN 2016 | DOI: 10.1002/jat.3279

      Recently, we have reported the genotoxicity of 20 nm nanosilver evaluated using the in vitro cytokinesis-block micronucleus (CBMN) assay. In this study, we evaluated the genotoxic potential of 50 nm nanosilver of the same shape, composition, surface charge, obtained from the same commercial source, under the same experimental conditions and the same genotoxic CBMN endpoint used for the previously tested 20 nm silver. The ionic silver (silver acetate) was also evaluated under the same conditions. Results of our study show that up to the concentrations tested in these cell types, the smaller (20 nm) nanosilver induces micronucleus formation in both the cell types but the larger (50 nm) nanosilver and the ionic silver provide much weaker response compared with controls under the same conditions.

    5. The responses of immune cells to iron oxide nanoparticles (pages 543–553)

      Yaolin Xu, Jennifer A. Sherwood, Kimberly H. Lackey, Ying Qin and Yuping Bao

      Article first published online: 28 JAN 2016 | DOI: 10.1002/jat.3282

      Surface coating effects on nanoparticle cellular uptake, toxicity, and ability to trigger immune response were evaluated on human monocyte cell line using iron oxide nanoparticles. The cells were treated with nanoparticles of three types of coatings (negatively charged polyacrylic acid-PAA, positively charged polyethylenimine-PEI, and neutral polyethylene glycol-PEG). Cell viability and the expression of TNF-α and TLR2 were used to quantify the toxicity and immune response.

    6. Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos (pages 554–567)

      Santhanamari Ganesan, Naveenkumar Anaimalai Thirumurthi, Azhwar Raghunath, Savitha Vijayakumar and Ekambaram Perumal

      Article first published online: 23 OCT 2015 | DOI: 10.1002/jat.3224

      We evaluated the acute and sub-lethal oxidative stress and teratogenic effects of CuO-NPs to zebrafish embryos. The results showed an increase in oxidants with a decrease in antioxidants on treatment with CuO-NPs. In addition, distinct non-axial and axial malformations along with apoptosis were observed in the developing embryos. This study will expand our current knowledge on the ecotoxicological effects of CuO-NPs and will pave way for unraveling the molecular mechanisms in causing these deleterious effects.

    7. Distribution of single wall carbon nanotubes in the Xenopus laevis embryo after microinjection (pages 568–578)

      Brian D. Holt, Joseph H. Shawky, Kris Noel Dahl, Lance A. Davidson and Mohammad F. Islam

      Article first published online: 28 OCT 2015 | DOI: 10.1002/jat.3255

      Single wall carbon nanotubes (SWCNTs) have superlative properties for biological applications, but toxicity studies have yielded inconsistent results. To minimize confounding material effects, we utilized purified, length-selected, individualized SWCNTs. We microinjected high concentrations into the embryogenesis model, Xenopus laevis, and determined that SWCNTs were not toxic, remained individualized and localized within the microinjected cells' progeny. Fluorescently labeling subcellular compartments demonstrated no alterations to subcellular structures and perinuclear subcellular localization. These results suggest that purified, dispersed SWCNTs may be candidate materials for biological applications.

    8. Developing Xenopus embryos recover by compacting and expelling single wall carbon nanotubes (pages 579–585)

      Brian D. Holt, Joseph H. Shawky, Kris Noel Dahl, Lance A. Davidson and Mohammad F. Islam

      Article first published online: 7 JUL 2015 | DOI: 10.1002/jat.3203

      Single wall carbon nanotubes are being developed for wide-ranging applications. However, understanding the direct exposure to Xenopus laevis, a development model, is lacking. We found superficial microinjection of nanotubes suspended with Pluronic F127 into one- to two-cell embryos resulted in the formation and expulsion of compacted, nanotube-filled masses. Expulsion is dramatically different from typical distribution throughout the embryo. Previous studies microinjecting other nanomaterials often report toxicity, yet our results demonstrate recovery, which we speculate results from Pluronic F127's membrane activity and nanotubes’ large aspect ratio.

    9. Effects of urban particulate matter with high glucose on human monocytes U937 (pages 586–595)

      Yue Zhang, Yiqun Mo, Aihua Gu, Rong Wan, Qunwei Zhang and David J. Tollerud

      Article first published online: 14 JUL 2015 | DOI: 10.1002/jat.3198

      This study examined the effects of urban particulate matter (U-PM) with or without high glucose on human monocytes U937. The results showed that exposure of monocytes to U-PM alone caused ROS generation, increased p38 phosphorylation, up-regulation of MMP-2, MMP-9 and proinflammatory cytokines IL-1β and IL-8, and increased activity of pro-MMP-2 and pro-MMP-9. These effects were enhanced significantly when cells were exposed to U-PM with high glucose. Our findings have important implications in understanding the health effects of PM on diabetics.

    10. The toxic effects of indoor atmospheric fine particulate matter collected from allergic and non-allergic families in Wuhan on mouse peritoneal macrophages (pages 596–608)

      Biao Yan, Jinquan Li, Junhui Guo, Ping Ma, Zhuo Wu, ZhenHao Ling, Hai Guo, Yoshino Hiroshi, U. Yanagi, Xu Yang, Shengwei Zhu and Mingqing Chen

      Article first published online: 24 AUG 2015 | DOI: 10.1002/jat.3217

      The association between allergic symptoms in children and exposure to PM2.5 has not fully elucidated, especially the role of PM2.5 from indoor environment involved in allergy or non-allergy is unknown. In this study, indoor PM2.5 from the homes of schoolchildren with allergic symptoms and those of healthy ones were analyzed. It suggested that oxidative stress may contribute to PM2.5-induced toxicity, and PM2.5 from allergic indoor environment produced more serious toxic effects and inflammatory response than that from non-allergic indoor environment.

    11. Overproduction of reactive oxygen species and activation of MAPKs are involved in apoptosis induced by PM2.5 in rat cardiac H9c2 cells (pages 609–617)

      Jing Cao, Gang Qin, Ruizan Shi, Feng Bai, Guangzhao Yang, Mingsheng Zhang and Jiyuan Lv

      Article first published online: 15 OCT 2015 | DOI: 10.1002/jat.3249

      We present novel findings on the regulatory mechanisms of PM2.5-induced myocardiocyte apoptosis. PM2.5-induced apoptosis was associated with enhanced intracellular ROS production and mediated, at least partially, by a caspase-3-dependent, mitochondria/Bcl-2 death pathway via the MAPKs signaling pathway in H9c2 cells. Our findings shed light on the stress signaling pathway involved in PM2.5-induced apoptotic effects in H9c2 cells. The MAPKs signaling pathway could be a new promising target for clinical therapeutic strategies against PM2.5-induced cardiac injury.

    12. Pulmonary toxicity of indium-tin oxide production facility particles in rats (pages 618–626)

      Melissa A. Badding, Natalie R. Fix, Marlene S. Orandle, Mark W. Barger, Katherine M. Dunnick, Kristin J. Cummings and Stephen S. Leonard

      Article first published online: 15 OCT 2015 | DOI: 10.1002/jat.3253

      Indium-tin oxide (ITO) is used to make transparent conductive coatings for electronics. Exposures to indium-containing particles in the workplace have increased in recent years as the demand for consumer electronics continues to rise. Here we examined the pulmonary toxicity of three different particle samples that were collected at various stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO and ventilation dust particles each induced inflammation and damage in the lungs of rats over a time course.

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