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Preclinical Safety Evaluation of Human Mesenchymal Stem Cell Transplantation in Cerebrum of Nonhuman Primates
The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 x 105 cells/kg), high dose (2.5 x 106 cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS w...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Feng, M., Li, Y., Han, Q., Bao, X., Yang, M., Zhu, H., Li, Q., Wei, J., Ma, W., Gao, H., An, Y., Zhao, R. C., Qin, C., Wang, R. Tags: Original Articles Source Type: research

Oral Toxicity Evaluation of Thiodiglycol in Sprague-Dawley Rats
Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Angerhofer, R. A., Michie, M. W., Leach, G. J., Johnson, M. S., Reddy, G. Tags: Original Articles Source Type: research

Mechanistic Insights of Sulfur Mustard-Induced Acute Tracheal Injury in Rats
Sulfur mustard (SM) is believed to be a major threat to civilian populations because of the persistent asymmetric threat by nonstate actors, such as terrorist groups, the ease of synthesis and handling, and the risk of theft from stockpiles. The purpose of this study was to establish mechanisms of acute tracheal injury in rats induced by SM using histopathologic, immunohistochemical, and biochemical parameters. Male rats (Sprague-Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM. Animals were euthanized 6-, 24-, 48-, and 72-hour postexposure, and intracavitary blood samples from the heart a...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Zhu, X.-J., Xu, R., Meng, X., Chu, H.-B., Zhao, C., Lian, C.-J., Wang, T., Guo, W.-J., Zhang, S.-M. Tags: Original Articles Source Type: research

Cellular Deficiency of Werner Syndrome Protein or RECQ1 Promotes Genotoxic Potential of Hydroquinone and Benzo[a]pyrene Exposure
The 5 known RecQ helicases in humans (RECQ1, BLM, WRN, RECQL4, and RECQ5) have demonstrated roles in diverse genome maintenance mechanisms but their functions in safeguarding the genome from environmental toxicants are poorly understood. Here, we have evaluated a potential role of WRN (mutated in Werner syndrome) and RECQ1 (the most abundant homolog of WRN) in hydroquinone (HQ)- and benzo[a]pyrene (BaP)-induced genotoxicity. Silencing of WRN or RECQ1 expression in HeLa cells increased their sensitivity to HQ and BaP but elicited distinct DNA damage response. The RECQ1-depleted cells exhibited increased replication protein ...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Garige, M., Sharma, S. Tags: Original Articles Source Type: research

Assessment of 3-Nitro-1,2,4-triazol-5-one as a Potential Endocrine Disrupting Chemical in Rats Using the Hershberger and Uterotrophic Bioassays
This study assessed endocrine disruption as a potential mechanism for these reproductive effects via the Hershberger and uterotrophic bioassays. These assays are 2 of the US Environmental Protection Agency’s tier 1 in vivo screens for the Endocrine Disruptor Screening Program that measure differences in androgen- and estrogen-sensitive tissue weights in castrated and ovariectomized rats. The gonadectomized rats were orally exposed to NTO in a corn oil vehicle at doses of 250, 500, or 1000 mg/kg body weight (bw)/d for 10 and 3 days for the Hershberger and uterotrophic assays, respectively, according to standard protoc...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Quinn, M. J., Bannon, D. I., Jackovitz, A. M., Hanna, T. L., Shiflett, A. A., Johnson, M. S. Tags: Original Articles Source Type: research

HaloJ: An ImageJ Program for Semiautomatic Quantification of DNA Damage at Single-Cell Level
Although Halo assay is a fast and more economic technique, it is not popular compared to comet assay for the measurement of DNA damage. One of the reasons behind this was nonavailability of suitable user-friendly program. Currently, most of the researchers were analyzing halo images manually using image analysis software (Scion Image or ImageJ). To address this problem, I have developed a semiautomatic halo analysis ImageJ program, HaloJ, and applied in the assessment of DNA damage at the single-cell level. In this article, we have shown that data obtained from the HaloJ program have a very good correlation with the data o...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Maurya, D. K. Tags: Original Articles Source Type: research

New Method for Sperm Evaluation by 3-Dimensional Laser Scanning Microscopy in Different Laboratory Animal Species
Sperm analysis is one of the end points in reproductive toxicology studies. Different methods for quantitative sperm analysis have been described. For qualitative morphological sperm analysis, either such techniques or smears of sperm and histological sperm staging are in use. Any of these methods provides morphological results on a light microscopy level. Laser scanning microscopy is a technique using a focused laser for scanning an object. The Olympus 3D Laser Scanning Microscope LEXT OLS4000 with optional possibilities of differential interference contrast provides a microscopic method for visualizing microasperities, w...
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Weber, K., Waletzky, A., Fendl, D., Ordonez, P., Takawale, P., Hein, F., Riedel, W., Konig, A., Kunze, M., Leoni, A.-L., Rivera, J., Quirici, R., Romano, I., Paepke, S., Okazaki, Y., Hardisty, J. F. Tags: Original Articles Source Type: research

Strengthening the Peer Review Process for the International Journal of Toxicology
(Source: International Journal of Toxicology)
Source: International Journal of Toxicology - October 9, 2014 Category: Toxicology Authors: Brock, W. J. Tags: Editor ' s Note Source Type: research

Safety Assessment of Vitis vinifera (Grape)-Derived Ingredients as Used in Cosmetics
The Cosmetic Ingredient Review Expert Panel (Panel) assessed the safety of 24 Vitis vinifera (grape)-derived ingredients and found them safe in the present practices of use and concentration in cosmetics. These ingredients function in cosmetics mostly as skin-conditioning agents, but some function as antioxidants, flavoring agents, and/or colorants. The Panel reviewed the available animal and clinical data to determine the safety of these ingredients. Additionally, some constituents of grapes have been assessed previously for safety as cosmetic ingredients by the Panel, and others are compounds that have been discussed in ...
Source: International Journal of Toxicology - October 8, 2014 Category: Toxicology Authors: Fiume, M. M., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G., Shank, R. C., Slaga, T. J., Snyder, P. W., Andersen, F. A. Tags: Articles Source Type: research

Safety Assessment of Modified Terephthalate Polymers as Used in Cosmetics
The safety of 6 modified terephthalate polymers as cosmetic ingredients was assessed. These ingredients mostly function as exfoliants, bulking agents, hair fixatives, and viscosity-increasing agents—nonaqueous. Polyethylene terephthalate (PET) is used in leave-on products up to 100% and in rinse-off products up to 2%. The Cosmetic Ingredient Review Expert Panel (Panel) considered that the PET used in cosmetics is chemically equivalent to that used in medical devices. The Panel determined that the Food and Drug Administration’s determination of safety of PET in several medical devices, which included human and a...
Source: International Journal of Toxicology - October 8, 2014 Category: Toxicology Authors: Becker, L. C., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G., Shank, R. C., Slaga, T. J., Snyder, P. W., Andersen, F. A. Tags: Articles Source Type: research

Safety Assessment of 6-Hydroxyindole as Used in Cosmetics
The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 6-hydroxyindole, which functions as an oxidative hair dye ingredient. The Panel considered relevant animal and human data provided in this safety assessment and concluded that 6-hydroxyindole is safe for use in oxidative hair dye formulations. (Source: International Journal of Toxicology)
Source: International Journal of Toxicology - October 8, 2014 Category: Toxicology Authors: Burnett, C. L., Heldreth, B., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G., Shank, R. C., Slaga, T. J., Snyder, P. W., Andersen, F. A. Tags: Articles Source Type: research

Amended Safety Assessment of Hypericum Perforatum-Derived Ingredients as Used in Cosmetics
The Cosmetic Ingredient Review Expert Panel (Panel) has issued an amended safety assessment of 7 Hypericum perforatum-derived ingredients as used in cosmetics. A common name for this plant is St John wort. These ingredients function in cosmetics as skin-conditioning agents—miscellaneous and antimicrobial agents. The Panel reviewed relevant animal and human data related to the H perforatum-derived ingredients. Because formulators may use more than 1 botanical ingredient in a formulation, caution was urged to avoid levels of toxicological concern for constituent chemicals and impurities. The Panel concluded that H perf...
Source: International Journal of Toxicology - October 8, 2014 Category: Toxicology Authors: Becker, L. C., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G., Shank, R. C., Slaga, T. J., Snyder, P. W., Andersen, F. A. Tags: Articles Source Type: research

Book Review: Genomic Biomarkers for Pharmaceutical Development--Advancing Personalized Health Care
(Source: International Journal of Toxicology)
Source: International Journal of Toxicology - August 5, 2014 Category: Toxicology Authors: Budny, J. A. Tags: Book Review Source Type: research

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain
Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopam...
Source: International Journal of Toxicology - August 5, 2014 Category: Toxicology Authors: Abhilash, M., Alex, M., Mathews, V. V., Nair, R. H. Tags: Regular Articles Source Type: research

Aspartame Administration and Insulin Treatment Altered Brain Levels of CYP2E1 and CYP3A2 in Streptozotocin-Induced Diabetic Rats
This study demonstrates that aspartame consumption and insulin treatment in a juvenile diabetic rat model leads to increase in cytochrome P450 (CYP) 2E1 and CYP3A2 isozymes in brain. Diabetes mellitus was induced in postweaned 21-day-old Wistar male rat by streptozotocin. Animals were randomly assigned to one of the following groups: untreated control, diabetic (D), D-insulin, D-aspartame, or the D-insulin + aspartame-treated group. Brain and liver tissue samples were used to analyze the activity of CYP2E1 and CYP3A2 and protein levels. Our results indicate that combined treatment with insulin and aspartame in juvenile dia...
Source: International Journal of Toxicology - August 5, 2014 Category: Toxicology Authors: Nosti-Palacios, R., Gomez-Garduno, J., Molina-Ortiz, D., Calzada-Leon, R., Dorado-Gonzalez, V. M., Vences-Mejia, A. Tags: Regular Articles Source Type: research