International Journal of Toxicology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Book Review: Toxicologic Pathology: Nonclinical Safety Assessment
(Source: International Journal of Toxicology)
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Genter, M. B. Tags: Book Reviews Source Type: research

Book Review: Handbook of Toxicology
(Source: International Journal of Toxicology)
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Kapp, R. W. Tags: Book Reviews Source Type: research

2,4,6-Trichlorophenol Cytotoxicity Involves Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis
This study aims to evaluate the cytotoxicity and potential mechanisms of 2,4,6-trichlorophenol (2,4,6-TCP) in mouse embryonic fibroblasts. Our results show that 2,4,6-TCP causes morphological changes and reduces cell viability. The overproduction of reactive oxygen species, the upregulation of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HMOX1) messenger RNA (mRNA) expressions, and the nuclear translocation of Nrf2 protein demonstrate that 2,4,6-TCP induces oxidative stress, and the Nrf2/HMOX1 pathway might be involved in 2,4,6-TCP-induced antioxidative response. Simultaneously, our data also demonstrate...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Zhang, X., Zhang, X., Niu, Z., Qi, Y., Huang, D., Zhang, Y. Tags: Regular Articles Source Type: research

A Preliminary Safety Evaluation of Polyhexamethylene Guanidine Hydrochloride
Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD50 for PHMGH was estimated to be 600 mg/kg (ie LC50 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD50) of 600 mg/kg ...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Asiedu-Gyekye, I. J., Mahmood, S. A., Awortwe, C., Nyarko, A. K. Tags: Regular Articles Source Type: research

Impact of Sodium Arsenite on Chromosomal Aberrations With Respect to Polymorphisms of Detoxification and DNA Repair Genes
This study was conducted to determine the association between arsenic exposure and polymorphisms of genes involved in detoxification (glutathione S-transferase T1 [GSTT1], glutathione S-transferase M1 [GSTM1], glutathione S-transferase O2 [GSTO2], catalase [CAT], and NAD(P)H quinone oxidoreductase1 [NQO1]) as well as nonhomologous end joining DNA repair genes (XRCC4, XRCC5, and XRCC6) with induction of chromosomal aberrations. The participants consisted of 123 healthy males who were genotyped using polymerase chain reaction-based methods. Primary cultures of whole blood were treated with sodium arsenite (NaAsO2; iAs(III); ...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Azizian-Farsani, F., Rafiei, G., Saadat, M. Tags: Regular Articles Source Type: research

The Response of Human Nasal and Bronchial Organotypic Tissue Cultures to Repeated Whole Cigarette Smoke Exposure
We report on a repeated whole mainstream CS exposure of nasal and bronchial organotypic tissue cultures that mimic the morphological, physiological, and molecular attributes of the human respiratory tract. Despite the similar cellular staining and cytokine secretion in both tissue types, the transcriptomic analyses in the context of biological network models identified similar and diverse biological processes that were impacted by CS-exposed nasal and bronchial cultures. Our results demonstrate that nasal and bronchial tissue cultures are appropriate in vitro models for the assessment of CS-induced adverse effects in the r...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Talikka, M., Kostadinova, R., Xiang, Y., Mathis, C., Sewer, A., Majeed, S., Kuehn, D., Frentzel, S., Merg, C., Geertz, M., Martin, F., Ivanov, N. V., Peitsch, M. C., Hoeng, J. Tags: Regular Articles Source Type: research

Toxicodynamic and Toxicokinetic Descriptors of Combined Chromium (VI) and Nickel Toxicity
After repeated intraperitoneal injections of nickel and chromium (VI) salts to rats, we found, and confirmed by mathematical modeling, that their combined subchronic toxicity can either be of additive type or depart from it (predominantly toward subadditivity) depending on the effect assessed. Against the background of moderate systemic toxicity, the combination under study proved to possess a marked additive genotoxicity assessed by means of the random amplification of polymorphic DNA test. We also demonstrated that chromium and nickel reciprocally influenced the retention of these metals in some organs (especially in the...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Minigaliyeva, I. A., Katsnelson, B. A., Privalova, L. I., Gurvich, V. B., Panov, V. G., Varaksin, A. N., Makeyev, O. H., Sutunkova, M. P., Loginova, N. V., Kireyeva, E. P., Grigoryeva, E. V., Slyshkina, T. V., Ganebnykh, E. V., Grebenkina, S. V. Tags: Regular Articles Source Type: research

Relationship Between Drug Structure and Minimal Inhibitory Concentration Value Used for Acceptable Daily Intake Analysis
This article demonstrated that, despite the complexity of the MIC value used as the end point, it is possible to validate the model in a limited extent. (Source: International Journal of Toxicology)
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Grabowski, T., Jaroszewski, J. J., Gad, S. C., Feder, M. Tags: Regular Articles Source Type: research

New Allometric Scaling Relationships and Applications for Dose and Toxicity Extrapolation
Allometric scaling between metabolic rate, size, body temperature, and other biological traits has found broad applications in ecology, physiology, and particularly in toxicology and pharmacology. Basal metabolic rate (BMR) was observed to scale with body size and temperature. However, the mass scaling exponent was increasingly debated whether it should be 2/3, 3/4, or neither, and scaling with body temperature also attracted recent attention. Based on thermodynamic principles, this work reports 2 new scaling relationships between BMR, size, temperature, and biological time. Good correlations were found with the new scalin...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Cao, Q., Yu, J., Connell, D. Tags: Regular Articles Source Type: research

Trend Analysis of Body Weight Parameters, Mortality, and Incidence of Spontaneous Tumors in Tg.rasH2 Mice
Carcinogenicity studies have been performed in conventional 2-year rodent studies for at least 3 decades, whereas the short-term carcinogenicity studies in transgenic mice, such as Tg.rasH2, have only been performed over the last decade. In the 2-year conventional rodent studies, interlinked problems, such as increasing trends in the initial body weights, increased body weight gains, high incidence of spontaneous tumors, and low survival, that complicate the interpretation of findings have been well established. However, these end points have not been evaluated in the short-term carcinogenicity studies involving the Tg.ras...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Paranjpe, M. G., Denton, M. D., Vidmar, T., Elbekai, R. H. Tags: Regular Articles Source Type: research

Safety Assessment of EPA-Rich Polar Lipid Oil Produced From the Microalgae Nannochloropsis oculata
Almega PL is an eicosapentaenoic acid-rich -3 oil that is isolated from Nannochloropsis oculata algae and developed as a dietary supplement. The safety of the algal oil was evaluated in 14- and 90-day studies in Sprague-Dawley rats by oral gavage at dose levels of 0, 250, 500, and 2500 mg/kg/d and 0, 200, 400, and 2000 mg/kg/d, respectively. No mortalities occurred and no signs of toxicity were observed during the studies. No treatment-related effects were seen for body weight, food consumption, ophthalmology, neurological effects, urinalysis, clinical pathology, gross pathology, organ weights, or histopathology. Although ...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Kagan, M. L., Sullivan, D. W., Gad, S. C., Ballou, C. M. Tags: Regular Articles Source Type: research

Acute Toxicity of Subcutaneously Administered Vitamin E Isomers Delta- and Gamma-Tocotrienol in Mice
The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysi...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Swift, S. N., Pessu, R. L., Chakraborty, K., Villa, V., Lombardini, E., Ghosh, S. P. Tags: Regular Articles Source Type: research

Nonclinical Safety of the Sodium-Glucose Cotransporter 2 Inhibitor Empagliflozin
Empagliflozin, a selective inhibitor of the renal tubular sodium-glucose cotransporter 2, was developed for treatment of type 2 diabetes mellitus. Nonclinical safety of empagliflozin was studied in a battery of tests to support global market authorization. Safety pharmacology studies indicated no effect of empagliflozin on measures of respiratory or central nervous system function in rats or cardiovascular safety in telemeterized dogs. In CD-1 mouse, Wistar Han rat, or beagle dogs up to 13, 26, or 52 weeks of treatment, respectively, empagliflozin exhibited a toxicity profile consistent with secondary supratherapeutic phar...
Source: International Journal of Toxicology - December 30, 2014 Category: Toxicology Authors: Bogdanffy, M. S., Stachlewitz, R. F., van Tongeren, S., Knight, B., Sharp, D. E., Ku, W., Hart, S. E., Blanchard, K. Tags: Regular Articles Source Type: research

Tavaborole, a Novel Boron-Containing Small Molecule for the Topical Treatment of Onychomycosis, Is Noncarcinogenic in 2-Year Carcinogenicity Studies
Tavaborole, a cyclized boronic acid, has been approved by the Food and Drug Administration for the topical treatment of toenail onychomycosis. This novel, low-molecular-weight pharmaceutical compound has broad-spectrum antifungal activity against dermatophytes, yeasts, and molds responsible for the disease. Tavaborole was tested in 2-year carcinogenicity studies in mice (once daily dermal administration) and rats (once daily by oral gavage) as part of the extensive nonclinical safety program. There was no evidence of tavaborole-related neoplasms observed in either study. Based on the data gathered from these 2 carcinogenic...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Ciaravino, V., Coronado, D., Lanphear, C., Shaikh, I., Ruddock, W., Chanda, S. Tags: Original Articles Source Type: research

Cadmium Inhibits Neurite Outgrowth in Differentiating Human SH-SY5Y Neuroblastoma Cells
Cadmium, a highly ubiquitous heavy metal, is well known to induce neurotoxicity. However, the underlying mechanism of cadmium-mediated neurotoxicity remains unclear. We have studied cadmium inhibition of neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). Cadmium, at a concentration of 3 μmol/L, had no significant effect on the viability of differentiating SH-SY5Y cells. However, the neurite outgrowth of the differentiating SH-SY5Y cells 48 hours after cadmium treatment (1-3 μmol/L cadmium) was significantly inhibited in a dose-dependent manner. Treatmen...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Pak, E. J., Son, G. D., Yoo, B. S. Tags: Original Articles Source Type: research