Journal of Applied Toxicology

Cover image for Vol. 35 Issue 1

January 2015

Volume 35, Issue 1

Pages 1–115

  1. Review Article

    1. Top of page
    2. Review Article
    3. Research Articles
    1. Animal models for percutaneous absorption (pages 1–10)

      Eui Chang Jung and Howard I. Maibach

      Article first published online: 27 OCT 2014 | DOI: 10.1002/jat.3004

      Animal models are important tools to predict human in vivo percutaneous absorption/penetration. Monkey, pig, rat, rabbit, guinea pig, hairless rat, hairless mouse, hairless guinea pig and hairless dog are the most used animals. Each animal model has its own advantages and weakness. We reviewed the original papers published after 1993 that described permeability of both animal skin and human skin. It showed that monkey, pig and hairless guinea pig are most predictive of human skin absorption.

  2. Research Articles

    1. Top of page
    2. Review Article
    3. Research Articles
    1. Fish multigeneration test with preliminary short-term reproduction assay for estrone using Japanese medaka (Oryzias latipes) (pages 11–23)

      Ataru Nakamura, Ikumi Tamura, Hitomi Takanobu, Masumi Yamamuro, Taisen Iguchi and Norihisa Tatarazako

      Article first published online: 12 FEB 2014 | DOI: 10.1002/jat.2981

      The long-term adverse effects of estrone on aquatic wildlife is of great concern. We exposed Japanese medaka (Oryzias latipes) to estrone (5.74-91.4 ng l–1) for 27 weeks across three generations. We found a decline in egg production and fertility in the second generation exposed to 91.4 ng l–1, much lower than known concentrations in urban rivers. Furthermore, histopathological abnormalities observed in the third generation exposed to 47.1 ng l–1 suggest that estrone exerts severe effects on the third or later generations.

    2. Benchmark dose of cadmium concentration in rice for renal effects in a cadmium-polluted area in Japan (pages 24–28)

      Kazuhiro Nogawa, Teruhiko Kido, Muneko Nishijo, Hideaki Nakagawa and Yasushi Suwazono

      Article first published online: 30 JAN 2014 | DOI: 10.1002/jat.2982

      We applied an updated hybrid approach to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of cadmium concentration in rice for renal effects in humans. The BMDL of cadmium in rice for β2-microglobulin was 0.25 mg/kg in men and 0.24 mg/kg in women. These estimated BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure especially in terms of the food standard of cadmium concentration in rice.

    3. Development and utilization of an ex vivo bromodeoxyuridine local lymph node assay protocol for assessing potential chemical sensitizers (pages 29–40)

      W. C. Williams, C. Copeland, E. Boykin, S. J. Quell and D. M. Lehmann

      Article first published online: 14 FEB 2014 | DOI: 10.1002/jat.2983

      The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. We developed an ex vivo BrdU-labeling procedure eliminating the need for in vivo injections. The ex vivo BrdU LLNA accurately predicted the sensitization potential of known sensitizers and non-sensitizers. This ex vivo BrdU labeling method offers predictive capacity comparable to previously established LLNA protocols while eliminating animal injections and the use of radioisotope.

    4. The effect of diesel exhaust exposure on blood–brain barrier integrity and function in a murine model (pages 41–47)

      Sayeh Heidari Nejad, Ryusuke Takechi, Benjamin J. Mullins, Corey Giles, Alexander N. Larcombe, Dean Bertolatti, Krassi Rumchev, Satvinder Dhaliwal and John Mamo

      Article first published online: 30 JAN 2014 | DOI: 10.1002/jat.2985

      Epidemiological studies indicate that exposure to diesel exhaust (DE) is associated with vascular-based disorders. An in vivo murine model was utilized to determine the effect of DE inhalation on neurovascular integrity. The study demonstrated that exposure to DE compromises the integrity and function of cerebral capillary vessels. Heightened neurovascular inflammation as a consequence of sub-chronic DE exposure may contribute to risk for neurovascular based disorders.

    5. Development of a multiparametric in vitro model of skin sensitization (pages 48–58)

      Muriel Guyard-Nicodème, Eloise Gerault, Marion Platteel, Olivier Peschard, Wilfried Veron, Philippe Mondon, Svinareff Pascal and Marc G. J. Feuilloley

      Article first published online: 3 FEB 2014 | DOI: 10.1002/jat.2986

      A new in vitro model of skin sensitizing potential based on the measure of 4 parameters, i.e. trans-cutaneous permeation (Factor A), haptenation (Factor B), sensitization cytokines production (Factor C) and acute toxicity (Factor D) was described. A total of 32 compounds regularly employed in cosmetics were tested in this model. The correlation with in vivo assays reached 81.2% and the safety of the test (risk of false negative) reached 96.8 %.

    6. You have full text access to this OnlineOpen article
      Microvesicle-associated microRNA expression is altered upon particulate matter exposure in healthy workers and in A549 cells (pages 59–67)

      Valentina Bollati, Laura Angelici, Giovanna Rizzo, Laura Pergoli, Federica Rota, Mirjam Hoxha, Francesco Nordio, Matteo Bonzini, Letizia Tarantini, Laura Cantone, Angela C. Pesatori, Pietro Apostoli, Andrea A. Baccarelli and Pier Alberto Bertazzi

      Article first published online: 7 FEB 2014 | DOI: 10.1002/jat.2987

      Cell-derived microvesicles (MVs) are found in plasma and may transfer signals between tissues. In this article, we report in-vivo and in-vitro studies demonstrating that Particulate Matter (PM) affects systemic MV signaling by inducing MV release from alveolar cells into plasma. In-vivo microRNA screening showed increased miR-128 level in plasma MVs after PM exposure. In-vitro experiments confirmed PM-induced release of miR-128 in MVs from A549 alveolar cells. Future studies are warranted to determine the roles of MVs in mediating PM effects.

    7. Establishment of a short-term, in vivo screening method for detecting chemicals with juvenile hormone activity using adult Daphnia magna (pages 75–82)

      Ryoko Abe, Haruna Watanabe, Masumi Yamamuro, Taisen Iguchi and Norihisa Tatarazako

      Article first published online: 30 JAN 2014 | DOI: 10.1002/jat.2989

      Juvenile hormone (JH) and JH agonists have been shown to induce male offspring production in Daphnia using OECD TG211. The critical period for JH action to induce male offspring is 7-8 h (only 1 h) before ovulation. For the purpose of the detection of JH-like chemicals, we improved and simplified TG211 Annex7 and enabled us to save time and effort. The validity of a new testing method was verified by the test of positive and negative control chemicals.

    8. Effects of cylindrospermopsin on a common carp leucocyte cell line (pages 83–89)

      Anna Sieroslawska and Anna Rymuszka

      Article first published online: 30 JAN 2014 | DOI: 10.1002/jat.2990

      Cylindrospermopsin (CYN) is a cytotoxin produced by different cyanobacterial species. The aim of the study was to elucidate the impact of cylindrospermopsin on a common carp (Cyprinus carpio L.) leucocyte cell line (CLC). The toxin at 10 and 1 µg ml–1 occurred to be evidently cytotoxic whereas at 0.1 µg ml–1 there were no effects on cell viability or cell number; however, a strong reduction of bacteria uptake was detected. The obtained results indicate that cylindrospermopsin may interfere with the basic functions of fish phagocytic cells.

    9. Molecular biomarkers of phospholipidosis in rat blood and heart after amiodarone treatment (pages 90–103)

      Nicola Bocchini, Mery Giantin, Federica Crivellente, Serena Ferraresso, Ivo Faustinelli, Mauro Dacasto and Patrizia Cristofori

      Article first published online: 18 FEB 2014 | DOI: 10.1002/jat.2992

      A set of phospholipidosis (PLD) biomarkers was identified in the blood and hearts of rats treated with amiodarone (AMD) using DNA microarrays. Overall, 545 and 8218 genes were modulated by AMD in hearts and blood, respectively; furthermore, some genes implicated in cellular phospholipid accumulation showed similar alterations. The usefulness of seven candidate genes was screened and confirmed by quantitative Real-Time PCR analysis. Presented data underscore the importance of transcriptional profiling in preclinical studies. Blood may be a surrogate tissue of cardiomyocyte PLD.

    10. Preliminary safety evaluation of a taurocholate-conjugated low-molecular-weight heparin derivative (LHT7): a potent angiogenesis inhibitor (pages 104–115)

      Farzana Alam, Seung Woo Chung, Seung Rim Hwang, Ji-young Kim, Jooho Park, Hyun Tae Moon and Youngro Byun

      Article first published online: 16 FEB 2014 | DOI: 10.1002/jat.2995

      In our previous studies, taurocholic acid (TA)-conjugated low-molecular-weight heparin derivative (LHT7) showed promising anti-angiogenic effects. For the development of this drug, LHT7, evaluation of its biological safety with mechanism-related side effects were performed. From this study, no other side effects have been found except for LHT7's accumulation in the liver and kidney owing its affinity to vascular endothelial growth factor (VEGF) and its saturation with TA at high doses.

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