Journal of Applied Toxicology

Cover image for Vol. 33 Issue 10

October 2013

Volume 33, Issue 10

Pages 1036–1192

  1. Research Articles

    1. Top of page
    2. Research Articles
    3. Short Communication
    4. Erratum
    1. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat (pages 1036–1043)

      Syed M. Nurulain, Georg Petroianu, Mohamed Shafiullah, Huba Kalász, Murat Oz, Tariq Saeed, Abdu Adem and Ernest Adeghate

      Version of Record online: 9 AUG 2012 | DOI: 10.1002/jat.2794

      There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure of paraoxon, an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. The results suggest that paraoxon neither induces nor exacerbates diabetes in experimental rats.

    2. Raman spectroscopy analysis and mapping the biodistribution of inhaled carbon nanotubes in the lungs and blood of mice (pages 1044–1052)

      Taylor Ingle, Enkeleda Dervishi, Alexandru R. Biris, Thikra Mustafa, Roger A. Buchanan and Alexandru S. Biris

      Version of Record online: 10 OCT 2012 | DOI: 10.1002/jat.2796

      Because of their small size, robust structure and unique characteristics, carbon nanotubes (CNTs) are increasingly being used in a variety of biomedical applications, materials and products. As their use increases, so does the probability of their unintended release and human exposure. Therefore, it is important to establish their potential biodistribution and biopersistence to better understand the potential effects of their exposure to humans.

    3. In vivo comet assay of multi-walled carbon nanotubes using lung cells of rats intratracheally instilled (pages 1053–1060)

      Makoto Ema, Shoji Masumori, Norihiro Kobayashi, Masato Naya, Shigehisa Endoh, Junko Maru, Masayo Hosoi, Fuyumi Uno, Madoka Nakajima, Makoto Hayashi and Junko Nakanishi

      Version of Record online: 31 AUG 2012 | DOI: 10.1002/jat.2810

      Multi-walled carbon nanotubes (MWCNTs) were intratracheally instilled as a single dose at 0.2 or 1.0 mg kg–1 or a repeated dose at 0.04 or 0.2 mg kg–1, once a week for 5 weeks, to male rats. Inflammatory changes were found in the lungs of rats after a single instillation and repeated instillation at both doses. MWCNTs had no potential for DNA damage in comet assays using the lung cells of rats given MWCNTs at doses causing inflammatory responses.

    4. No evidence of the genotoxic potential of gold, silver, zinc oxide and titanium dioxide nanoparticles in the SOS chromotest (pages 1061–1069)

      Sun-Hwa Nam, Shin Woong Kim and Youn-Joo An

      Version of Record online: 16 NOV 2012 | DOI: 10.1002/jat.2830

      This study investigated the genotoxicity of gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), zinc oxide nanoparticles (ZnO NPs), and titanium dioxide nanoparticles (TiO2 NPs) by using the SOS chromotest with E. coli PQ37. The four NPs and its ions, in a range of tested concentrations, exerted no effects in the SOS chromotest. They are classified as non-genotoxic on the basis of the SOS chromotest.

    5. Expression levels of neuroimmune biomarkers in hypothalamus of allergic mice after phthalate exposure (pages 1070–1078)

      Tin-Tin Win-Shwe, Rie Yanagisawa, Eiko Koike, Hiroshi Nitta and Hirohisa Takano

      Version of Record online: 13 NOV 2012 | DOI: 10.1002/jat.2835

      Previously, we demonstrated that maternal exposure to phthalates enhances atopic dermatitis in male mouse offspring. However, whether phthalate exposure affects neuroimmune biomarkers in allergic mice has not yet been studied. Di-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) are environmental chemicals that are commonly used as plasticizers. This study was designed to investigate the expression levels of neuroimmune biomarkers in the hypothalamus of a murine model of allergic asthma after phthalate exposure throughout juvenility until adulthood.

    6. Acute toxicity of zinc oxide nanoparticles to the rat olfactory system after intranasal instillation (pages 1079–1088)

      Lifeng Gao, Sheng-Tao Yang, Shaorui Li, Yuguang Meng, Haifang Wang and Hao Lei

      Version of Record online: 11 JAN 2013 | DOI: 10.1002/jat.2842

      ZnO nanoparticles are mass-produced nanomaterials. In this study, we evaluated the acute toxic effects of 30 nm-diameter ZnO nanoparticles after intranasal instillation by behavioral tests, magnetic resonance imaging and histology. It was shown ZnO nanoparticles instilled into the nasal cavity caused significant structural damages to rat olfactory epithelium (OE) and olfactory impairment. ZnO NP-induced OE damages are characterized by edema, degeneration of epithelial cells and increased blood vessel permeability. The possible toxicological mechanism might involve cellular energy metabolic dysfunction.

    7. Rat pancreatitis produced by 13-week administration of zinc oxide nanoparticles: biopersistence of nanoparticles and possible solutions (pages 1089–1096)

      Seung Hyeok Seok, Wan-Seob Cho, Jung Shin Park, Yirang Na, Ahram Jang, Hojoong Kim, Yujin Cho, Taesung Kim, Ji-Ran You, Sanghoon Ko, Byeong-Cheol Kang, Jong Kwon Lee, Jayoung Jeong and Jeong-Hwan Che

      Version of Record online: 13 FEB 2013 | DOI: 10.1002/jat.2862

      Zinc oxide (ZnO) nanoparticles (NPs) have been used for diverse applications including paints, cosmetics, biomedicine, and food. ZnO NPs can cause pancreatitis and anemia and this might be an important data for toxicity and risk assessment of ZnO NP in subchronic 13-week toxicity study vial oral route in rats. The bio-persistence of ZnO NPs after ingestion is key to their toxicity; the no-observed-adverse effect level (NOAEL) of ZnO NPs was found to be 268.4mgkg–1 per day for both sexes.

    8. Influence of the surface coating on the cytotoxicity, genotoxicity and uptake of gold nanoparticles in human HepG2 cells (pages 1111–1119)

      Sónia Fraga, Helena Faria, Maria Elisa Soares, José Alberto Duarte, Leonor Soares, Eulália Pereira, Cristiana Costa-Pereira, João Paulo Teixeira, Maria de Lourdes Bastos and Helena Carmo

      Version of Record online: 25 MAR 2013 | DOI: 10.1002/jat.2865

      This study comparatively evaluated the influence of surface coating [citrate(Cit) vs 11-mercaptoundecanoic acid(11-MUA)] on the uptake and toxicity of gold nanoparticles(AuNPs) in HepG2 cells. Both Cit- and MUA-AuNPs were observed either inside intracellular endosomes or in intercellular spaces. Under the tested conditions, they did not induce cytotoxicity. However, an inverse concentration-dependent increase of DNA damage was observed in Cit-AuNPs- but not in MUA-AuNPs-exposed cells. These data demonstrate the impact of surface properties in the biocompatibility and safety of AuNPs.

    9. Genomic biomarkers for cardiotoxicity in rats as a sensitive tool in preclinical studies (pages 1120–1130)

      Yoko Nishimura, Yuji Morikawa, Chiaki Kondo, Yutaka Tonomura, Ryou Fukushima, Mikinori Torii and Takeki Uehara

      Version of Record online: 4 APR 2013 | DOI: 10.1002/jat.2867

      Cardiotoxicity is an important issue in drug development. In the present study, we focused on 8 genes (Spp1, Fhl1, Timp1, Serpine1, Bcat1, Lmcd1, Rnd1 and Tgfb2) as candidate genomic biomarkers for cardiotoxicity in rats, and constructed an optimized support vector machine (SVM) model that was composed of Spp1 and Timp1. This multi-gene model exhibited advantages over classic tools commonly used for cardiotoxicity evaluations in rats, and the application of the model could potentially lead to the production of safer drugs.

    10. Nanosilver suppresses growth and induces oxidative damage to DNA in Caenorhabditis elegans (pages 1131–1142)

      Piper Reid Hunt, Bryce J. Marquis, Katherine M. Tyner, Sean Conklin, Nicholas Olejnik, Bryant C. Nelson and Robert L. Sprando

      Version of Record online: 1 MAY 2013 | DOI: 10.1002/jat.2872

      Studies on the effects of nanomaterial exposure in mammals are limited, and new methods for rapid risk assessment of nanomaterials are urgently required. The utility of C. elegans as an alternative model for toxicity screens was evaluated using 10 nanometer silver (10nmAg). Consistent with studies using mammalian in vitro and in vivo models, 10nmAg at 10 μg ml-1 reduced growth and induced oxidative damage to DNA, and ionic silver was found to be more toxic than 10nmAg to C. elegans.

    11. Preosteoblasts behavior in contact with single-walled carbon nanotubes synthesized by radio frequency induction thermal plasma using various catalysts (pages 1143–1155)

      Yasaman Alinejad, Nathalie Faucheux and Gervais Soucy

      Version of Record online: 26 APR 2013 | DOI: 10.1002/jat.2875

      When added on murine MC3T3-E1 preosteoblasts, single-walled carbon nanotubes (SWCNTs) produced by radio frequency induction thermal plasma with three catalyst mixtures drastically reduced cell viability in a dose-dependent manner. In contrast, the viability of preosteoblasts seeded on SWCNTs was slightly decreased at 24 h without apoptosis and the cells could proliferate within 48 h. Thus except mechanical disturbance, thermal plasma grown SWCNTs induced no severe cytotoxicity on preosteoblasts and therefore could be more deeply studied for bone applications.

    12. Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells (pages 1156–1164)

      Anxin Wang, Kefeng Pu, Bing Dong, Yang Liu, Liming Zhang, Zhijun Zhang, Wei Duan and Yimin Zhu

      Version of Record online: 18 JUN 2013 | DOI: 10.1002/jat.2877

      The cytotoxicity and genotoxicity of graphene oxide (GO) to human lung fibroblast (HLF) cells have been confirmed by performing methyl thiazolyl tetrazolium (MTT), sub-G1 and comet assays to the GO treated cells. The mechanism of toxic effect of GO was explored through examining the toxicity of modified GOs and oxidative stress of GO treated cells. The results showed that oxidative stress mediated by GO and the electronic charge on the surface of GO might explain the reason of its toxicity.

    13. Toxicity assessment of manganese oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral exposure (pages 1165–1179)

      Shailendra Pratap Singh, Monika Kumari, Srinivas I. Kumari, Mohammed F. Rahman, M. Mahboob and Paramjit Grover

      Version of Record online: 24 MAY 2013 | DOI: 10.1002/jat.2887

      Repeated oral doses of manganese oxide NPs and MPs were administered for 28 days to rats. The genotoxicity results demonstrated significant increase in DNA damage in leukocytes, micronuclei and chromosomal aberrations in bone marrow cells after exposure of MnO2-NPs at 1000, 300mg/kg/bw/day and MnO2-MPs at the dose of 1000mg/kgbw/day. Our findings showed significant biochemical and histopathological changes in various tissues. Significant biodistribution was found in all the tissues after treatment with MnO2 NPs and MPs in a dose dependent manner.

    14. Toxic effects of microcystin-LR on the HepG2 cell line under hypoxic and normoxic conditions (pages 1180–1186)

      Xin Zhang, Ping Xie, Xuezhen Zhang, Wenshan Zhou, Sujuan Zhao, Yanyan Zhao and Yan Cai

      Version of Record online: 27 APR 2012 | DOI: 10.1002/jat.2749

      Microcystins (MCs) are highly liver-specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear.

  2. Short Communication

    1. Top of page
    2. Research Articles
    3. Short Communication
    4. Erratum
    1. Transient alterations of the blood–brain barrier tight junction and receptor potential channel gene expression by chlorpyrifos (pages 1187–1191)

      Wen Li and Marion Ehrich

      Version of Record online: 18 MAY 2012 | DOI: 10.1002/jat.2762

      We previously demonstrated that exposure to very low concentrations of the organophosphorus insecticide chlorpyrifos (CPF) decreased electrical resistance across the blood–brain barrier (BBB) in vitro, indicating a loss of BBB integrity. This study examined the transient effects of CPF on expression of genes contributing to tight junctions of the BBB. The results suggest that altering gene expression for claudin5, transient receptor potential (canonical) channels (TRPC4), and zona occludens (ZO1) by CPF may directly contribute to BBB disruption, and that the alteration is reversible upon removal of CPF.

  3. Erratum

    1. Top of page
    2. Research Articles
    3. Short Communication
    4. Erratum
    1. You have free access to this content
      Atractyloside induces low contractile reaction of arteriolar smooth muscle through mitochondrial damage (page 1192)

      Rui Song, Huining Bian, Xuliang Huang and Ke-seng Zhao

      Version of Record online: 26 JUL 2013 | DOI: 10.1002/jat.2915

      This article corrects: