Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

April 2009

Volume 29, Issue 3

Pages 183–274

  1. Reviews

    1. Top of page
    2. Reviews
    3. Research Articles
    1. Collation, assessment and analysis of literature in vitro data on hERG receptor blocking potency for subsequent modeling of drugs' cardiotoxic properties (pages 183–206)

      Sebastian Polak, Barbara Wiśniowska and Jerzy Brandys

      Version of Record online: 5 NOV 2008 | DOI: 10.1002/jat.1395

      A concentration producing half-maximal block of the hERG potassium current (IC50) is a surrogate marker for proarrhythmic properties of compounds and is considered a test for cardiac safety of drugs or drug candidates. The IC50 values, obtained from data collected during electrophysiological studies, are highly dependent on experimental conditions. As for the in silico models' quality and performance, the data quality and consistency is a crucial issue. The main objective of our work was to collect and assess the hERG IC50 data available in accessible scientific literature to provide a high-quality data set for further studies.

  2. Research Articles

    1. Top of page
    2. Reviews
    3. Research Articles
    1. Phytoglycoprotein (150 kDa) isolated from Solanum nigrum Linne has a preventive effect on dextran sodium sulfate-induced colitis in A/J mouse (pages 207–213)

      Heon-Yeong Joo, Kwang Lim and Kye-Taek Lim

      Version of Record online: 5 NOV 2008 | DOI: 10.1002/jat.1396

      The purpose of this study is to investigate the preventive effect of glycoprotein (SNL glycoprotein, 150 kDa) on dextran sulfate sodium (DSS, 3%)-induced colitis in A/J mice. Our results showed that 20 mg/kg SNL glycoprotein significantly inhibits NO production, LDH release, and TBARS formation in serum, and has suppressive effect on activities of NF-κB (p50) and AP-1 (c-Jun), and also significantly regulates the expression of iNOS and COX-2 in the colon tissues. Thus, SNL glycoprotein has potential to prevent colon inflammation.

    2. Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix (pages 214–222)

      Rossana Pérez Aguilar, Susana Genta, Liliana Oliveros, Ana Anzulovich, María Sofía Giménez and Sara S. Sánchez

      Version of Record online: 6 NOV 2008 | DOI: 10.1002/jat.1399

      This study focuses on the effect of vitamin A deficiency on the morphology and extracellular proteins expression of the liver in adult Wistar rats.

      Vitamin A deficiency caused liver injury and that hepatic stellate cells underwent a process of activation in which they produced alpha smooth muscle actin and synthesized extracellular components (fibronectin, laminin and collagen type IV). These changes may be a factor predisposing to liver fibrosis. In consequence, vitamin A deprivation could affect human and animal health.

    3. In vitro estrogenicity of ambient particulate matter: contribution of hydroxylated polycyclic aromatic hydrocarbons (pages 223–232)

      Daniela Wenger, Andreas C. Gerecke, Norbert V. Heeb, Peter Schmid, Christoph Hueglin, Hanspeter Naegeli and Renato Zenobi

      Version of Record online: 19 NOV 2008 | DOI: 10.1002/jat.1400

      Ambient particulate matter (PM1) collected at an urban and a rural site in Switzerland induced estrogen receptor-mediated gene expression in human T47D cells. Five hydroxylated polycyclic aromatic hydrocarbons were assessed for their estrogenic potency using the ER-CALUX assay. Three of these hydroxy-PAHs were detected in all PM1 extracts and contributed to the overall estrogenic activity. PM1 estrogenicity was compared with concentrations of air pollutants and meteorological data in order to elucidate specific emission sources and formation processes of atmospheric xenoestrogens.

    4. Cytokine profiling of chemical allergens in mice: impact of mitogen on selectivity of response (pages 233–241)

      Rebecca Jane Dearman, Catherine Jean Betts, Helen Theresa Caddick and Ian Kimber

      Version of Record online: 19 NOV 2008 | DOI: 10.1002/jat.1401

      The potential application of cytokine profiling for discrimination between chemical contact and respiratory sensitizers has been investigated. Reference contact and respiratory sensitizers which induce type 1 and type 2 cytokine profiles, respectively, have been utilized. Culture conditions were critical for selectivity of the response, with mitogen resulting in a less discriminatory pattern of cytokine expression. The most optimal method is a 13 day exposure regime followed by cell culture at 107 ml-1 for 120 h in the absence of mitogen.

    5. Acute toxicity of parabens and their chlorinated by-products with Daphnia magna and Vibrio fischeri bioassays (pages 242–247)

      Masanori Terasaki, Masakazu Makino and Norihisa Tatarazako

      Version of Record online: 16 DEC 2008 | DOI: 10.1002/jat.1402

      The acute toxicity of 21 parabens and their chlorinated derivatives was investigated by Daphnia magna immobilization test and the inhibition of bioluminescence of Vibrio fischeri. D. magna toxicity showed a linear relationship with hydrophobicity. However, V. fischeri toxicity with hydrophobicity and with the degree of chlorination were poor. In addition, the results of the present study indicated that the V. fischeri test was more sensitive than the D. magna test for the determination of the acute toxicity of parabens.

    6. Nitroimidazole derivatives: non-randomness sister chromatid exchanges in human peripheral blood lymphocytes (pages 248–254)

      Marta Ana Carballo, Romari Alejandra Martinez and Marta Dolores Mudry

      Version of Record online: 11 DEC 2008 | DOI: 10.1002/jat.1403

      This study focuses on an evaluation of possible genomic targets, at a chromosomal level, of ornidazole and metronidazole using in vitro human peripheral blood culture. We observed a decrease in mitotic index (P < 0.001), an increase in sister chromatid exchanges frequency (P < 0.001) and no modifications in replication index. The analysis showed that SCE frequency per chromosome is not proportional to chromosome length (p<0.00001) as well as a high correlation between SCEs in certain chromosomal bands and the exposure to nitroimidazole derivatives.

    7. Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 1. Dose-finding study (pages 255–262)

      Lena Ernstgård, Birger Lind and Gunnar Johanson

      Version of Record online: 11 DEC 2008 | DOI: 10.1002/jat.1408

      A move from ‘standard’ white spirit (stdWS, 15–20% aromatics) to low aromatic or dearomatised white spirit (deWS) has been seen, as the latter are considered to carry a smaller risk of health effects. However, data on health risks of deWS on humans are sparse. The aim of this dose-finding study was to identify thresholds of irritation and central nervous system effects of the two types of white spirit, as a basis for more detailed studies.

    8. Acute effects of exposure to vapours of standard and dearomatized white spirits in humans. 2. Irritation and inflammation (pages 263–274)

      Lena Ernstgård, Anders Iregren, Stephanie Juran, Bengt Sjögren, Christoph van Thriel and Gunnar Johanson

      Version of Record online: 11 DEC 2008 | DOI: 10.1002/jat.1407

      Low aromatic and dearomatised white spirit (deWS) are often considered less hazardous to health than ‘standard’ or aromatic white sprit (stdWS). However, data on health effects of deWS in humans are sparse. The aim of this study was to compare deWS and stdWS with respect to irritation and inflammation. Twelve volunteers were exposed to 100 or 300 mg m−3 deWS (0.002% aromatics) or stdWS (19% aromatics), or to clean air, for 4 h.

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