Journal of Applied Toxicology

Cover image for Vol. 36 Issue 3

Editor-in-Chief: Philip W. Harvey

Impact Factor: 2.982

ISI Journal Citation Reports © Ranking: 2014: 27/88 (Toxicology)

Online ISSN: 1099-1263

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Recently Published Articles

  1. Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc

    Lina Chouchene, Elisabeth Pellegrini, Marie-Madeleine Gueguen, Nathalie Hinfray, François Brion, Benjamin Piccini, Olivier Kah, Khaled Saïd, Imed Messaoudi and Farzad Pakdel

    Article first published online: 9 FEB 2016 | DOI: 10.1002/jat.3285

    This study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, and the potential protective role of Zn against Cd-induced toxicity. Effects on the transcriptional activation of estrogen receptors, aromatase B protein expression and molecular expression of related genes were examined. Our results demonstrate that Cd acts as a potent anti-estrogen in vivo and in vitro, and that Cd-induced estradiol antagonism can be reversed, at the protein level, by Zn supplement.

  2. Integrated decision strategies for skin sensitization hazard

    Judy Strickland, Qingda Zang, Nicole Kleinstreuer, Michael Paris, David M. Lehmann, Neepa Choksi, Joanna Matheson, Abigail Jacobs, Anna Lowit, David Allen and Warren Casey

    Article first published online: 6 FEB 2016 | DOI: 10.1002/jat.3281

    The Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) evaluated a non-animal decision strategies to predict skin sensitization. Machine learning approaches integrated in vitro, in chemico and in silico data and six physicochemical properties for 120 substances to predict murine local lymph node assay (LLNA) outcomes. The seven models with the highest accuracy used a support vector machine with different combinations of predictor variables. The models outperformed individual non-animal methods and test batteries. This suggests that computational approaches are promising tools to effectively integrate data to identify potential skin sensitizers without animal testing.

  3. Gelucire and Gelucire-PEG400 formulations; tolerability in species used for non-clinical safety testing after oral (gavage) dosing

    Mikael Elander, Jette B. Boll, Anne S. Hojman and Allan D. Rasmussen

    Article first published online: 5 FEB 2016 | DOI: 10.1002/jat.3296

    A series of oral tolerability studies were conducted with Gelucire and Gelucire:PEG400 formulations in rats, dogs and minipigs in order to determine tolerable daily dose volumes in these species. It was concluded that Gelucire:PEG400 (90:10) was tolerated in Beagle dogs when administered at 1 ml kg–1 once daily for 39 weeks, and 100% Gelucire was tolerated in the rat and the minipig when administered once daily at 5 ml kg–1 for 5 days.

  4. Nanosuspension formulations of poorly water-soluble compounds for intravenous administration in exploratory toxicity studies: in vitro and in vivo evaluation

    Hisako Fujimura, Takao Komasaka, Taizo Tomari, Yasunori Kitano and Kouji Takekawa

    Article first published online: 5 FEB 2016 | DOI: 10.1002/jat.3280

    Nanosuspensions for intravenous injections were prepared using a mixer mill and zirconia beads with a vehicle of 2% (w/v) poloxamer 338, which was confirmed to induce no histamine release in dogs. Sterilized nanosuspensions were obtained by milling for 30 min, followed by autoclaving for 20 min at 121 °C and milling for 30 min (mill–autoclave–mill method). The enhancing effect of a nanosuspension on exposure in dogs and the versatility of the method were demonstrated.

  5. Depth-dependent stratum corneum permeability in human skin in vitro

    John Jay P. Cadavona, Hanjiang Zhu, Xiaoying Hui, Eui-Chang Jung and Howard I. Maibach

    Article first published online: 3 FEB 2016 | DOI: 10.1002/jat.3289

    The stratum corneum (SC) concentration–thickness profiles were determined for four model chemicals on intact and adhesive tape-stripped skin samples to clarify whether SC is a homogeneous barrier for chemical transport. Data analysis with the diffusion equation of Fick's second law permitted the chemical diffusion coefficient in SC. Results suggested the depth-dependency of SC permeability to panthenol, benzoic acid and butenafine; variation of the diffusion coefficient from the SC surface to the deeper layers agreed with a change in the diffusion coefficient over time in intact skin.

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