Journal of Applied Toxicology

Cover image for Vol. 34 Issue 10

October 2014

Volume 34, Issue 10

Pages 1068–1113

  1. Review Hypothesis

    1. Top of page
    2. Review Hypothesis
    3. Research Articles
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      A proposal to improve clarity and communication in the EU Classification process for chemicals for carcinogenicity and reproductive and developmental toxicity (pages 1068–1072)

      J. E. Doe

      Article first published online: 25 JUL 2014 | DOI: 10.1002/jat.3045

      The inability of the EU classification system to distinguish between carcinogens and reproductive toxicants with different levels of concern can cause problems in communicating to the users of chemicals the nature of the hazard presented by chemicals. Processes have been developed by the EU for assessing the degree of hazard for carcinogens and reproductive toxicants as high, medium or low. Using them more widely would bring the advantage of transparency, clarity of communication and certainty of the process.

    2. Diisocyanates, occupational asthma and IgE antibody: implications for hazard characterization (pages 1073–1077)

      Ian Kimber, Rebecca J. Dearman and David A. Basketter

      Article first published online: 25 JUL 2014 | DOI: 10.1002/jat.3041

      Sensitisation of the respiratory tract by chemicals associated with asthma is an important occupational health issue and remains a challenge to toxicologists. The failure to develop validated methods for hazard characterisation is in large part due to uncertainty about the relevant mechanisms, and in particular the role of IgE antibody. Here the relationship between respiratory allergy to diisocyanates and IgE antibody is explored, and the argument made that measurement of IgE antibody responses provides an appropriate basis for hazard identification.

  2. Research Articles

    1. Top of page
    2. Review Hypothesis
    3. Research Articles
    1. Long-term maintenance of HepaRG cells in serum-free conditions and application in a repeated dose study (pages 1078–1086)

      Sebastian Klein, Daniel Mueller, Valery Schevchenko and Fozia Noor

      Article first published online: 30 SEP 2013 | DOI: 10.1002/jat.2929

      HepaRG cells were maintained viable with constant CYP activities and liver-specific functions for 30 days in serum-free medium (SFM). The long-term viability and CYP activities were superior to those reported for primary human hepatocytes in vitro. Metabolic flux analysis indicates that the central carbon metabolism in SFM is comparable to standard conditions. This system can be applied for repeated dose toxicity assessments and will pave way for application on high content ‘omics’ platform in systems toxicology.

    2. Identification of metabolomic biomarkers for drug-induced acute kidney injury in rats (pages 1087–1095)

      Takeki Uehara, Akira Horinouchi, Yuji Morikawa, Yutaka Tonomura, Keiichi Minami, Atsushi Ono, Jyoji Yamate, Hiroshi Yamada, Yasuo Ohno and Tetsuro Urushidani

      Article first published online: 30 SEP 2013 | DOI: 10.1002/jat.2933

      Metabolomics involves the comprehensive and simultaneous determination of endogenous or exogenous metabolites in biological samples. The present study aimed to identify metabolomic biomarkers that could provide early and sensitive indication of nephrotoxicity in rats. Metabolomic analyses were performed using CE-TOFMS on rat plasma treated with several nephrotoxicants. Among a total of 169 metabolites identified, 3-methylhistidine, 3-indoxyl sulfate, and guanidoacetate were selected as candidate biomarkers, which may prove to be valuable plasma biomarkers for monitoring nephrotoxicity in rats.

    3. Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone (pages 1096–1103)

      Dietrich E. Lorke, Syed M. Nurulain, Mohamed Y. Hasan, Kamil Kuča and Georg A. Petroianu

      Article first published online: 17 OCT 2013 | DOI: 10.1002/jat.2939

      In search of a broad-spectrum prophylactic agent for organophosphate poisoning, the reversible AChE-inhibitors pyridostigmine, physostigmine, ranitidine, tacrine and K-27 (an experimental oxime) were tested as a pre-treatment before exposure to the organophosphate AChE-inhibitor terbufos sulfone. Their efficacy in reducing organophosphorus compound-induced mortality was assessed by Cox survival analysis. Best in vivo protection from terbufos sulfone-induced mortality was achieved by K-27. Prophylactic administration of an oxime, such as K-27, in case of imminent organophosphorus compound exposure may be a viable option.

    4. Rapid determination of quetiapine in blood by gas chromatography–mass spectrometry. Application to post-mortem cases (pages 1104–1108)

      Olga López-Guarnido, María Jesús Tabernero, Antonio F. Hernández, Lourdes Rodrigo and Ana M. Bermejo

      Article first published online: 11 OCT 2013 | DOI: 10.1002/jat.2944

      A simple, fast and sensitive method for the determination of quetiapine (QTP) in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry (GC/MS), previous derivatization with bis(trimethylsilyl)-trifluoroacetamide (BSTFA) and chorotrimethylsilane (TMCS) (99:1). The method validation included linearity with a correlation coefficient >0.99 over the range 0.02–1 µg mL-1.The limit of detection was 0.005 µg mL-1. The procedure was further applied to post mortem cases.

    5. Borrelidin has limited anti-cancer effects in bcl-2 overexpressing breast cancer and leukemia cells and reveals toxicity in non-malignant breast epithelial cells (pages 1109–1113)

      Diana Gafiuc, Marlene Weiß, Ioannis Mylonas and Ansgar Brüning

      Article first published online: 24 OCT 2013 | DOI: 10.1002/jat.2946

      Borrelidin is a macrolide antibiotic with selective cytotoxicity against endothelial cells and leukemia cells. While testing the efficacy of borrelidin on breast cancer cells, we noticed the occurrence of non-specific toxicity in non-malignant cells and pre-existing resistance mechanisms against borrelidin in breast cancer and leukemia cell lines. This may limit the use of borrelidin as a possible new anti-cancer drug and raises concerns about possible unspecific toxicities.